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A Phase 1/2 Study of PXD101 (Belinostat) in Combination With Cisplatin, Doxorubicin and Cyclophosphamide in the First Line Treatment of Advanced or Recurrent Thymic, Malignancies

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ClinicalTrials.gov Identifier: NCT01100944
Recruitment Status : Terminated (Principal investigator left the National Institutes of Health (NIH).)
First Posted : April 9, 2010
Results First Posted : November 15, 2016
Last Update Posted : August 10, 2017
Sponsor:
Information provided by (Responsible Party):
Arun Rajan, M.D., National Institutes of Health Clinical Center (CC)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Thymoma
Thymic Carcinoma
Intervention Drug: PXD101with cisplatin+doxorubicin+cyclophosphamide
Enrollment 26
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Belinostat 250mg/m(2) and Chemotherapy Belinostat 500mg/m(2) and Chemotherapy Belinostat and Chemotherapy at the Maximum Tolerated Dose(MTD)
Hide Arm/Group Description

Patients received 250mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Patients received 500mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Patients were treated with belinostat, doxorubicin, cisplatin and cyclophosphamide at the maximum tolerated dose derived from the phase I dose level.
Period Title: Dose Escalation Phase 1 Dose Level 1
Started 6 0 0
Completed 2 0 0
Not Completed 4 0 0
Reason Not Completed
Adverse Event             2             0             0
Discontinued due to treatment delay             1             0             0
Progressive Disease             1             0             0
Period Title: Dose Escalation Phase 1 Dose Level 2
Started 0 2 0
Completed 0 0 0
Not Completed 0 2 0
Reason Not Completed
Adverse Event             0             2             0
Period Title: Expansion Phase - Phase 2
Started 0 0 18
Completed 0 0 18
Not Completed 0 0 0
Arm/Group Title All Participants
Hide Arm/Group Description All participants who had at least one dose of Belinostat.
Overall Number of Baseline Participants 26
Hide Baseline Analysis Population Description
Per protocol, two group results, as well as single arm results are reported throughout the results data.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
<=18 years
0
   0.0%
Between 18 and 65 years
20
  76.9%
>=65 years
6
  23.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 26 participants
53.9  (13.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
Female
13
  50.0%
Male
13
  50.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
Hispanic or Latino
1
   3.8%
Not Hispanic or Latino
23
  88.5%
Unknown or Not Reported
2
   7.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
American Indian or Alaska Native
0
   0.0%
Asian
2
   7.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
4
  15.4%
White
20
  76.9%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 26 participants
26
ECOG Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
Grade 0
18
  69.2%
Grade 1
8
  30.8%
[1]
Measure Description:

Eastern Cooperative Oncology Group (ECOG).

Grade 0 is normal activity. Fully active, able to carry on all pre-disease performance without restriction.

Grade 1 is symptoms, but ambulatory. Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work).

Tumor Type   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
Thymoma
12
  46.2%
B1
2
   7.7%
B2
7
  26.9%
B3
3
  11.5%
Thymic carcinoma
14
  53.8%
[1]
Measure Description: The World Health Organization (WHO) classification of epithelial thymic malignancies shown under Thymoma are defined as type B1: histology - predominantly cortical thymoma, type B2: histology - cortical thymoma, and type B3: histology - well-differentiated thymoma.
Stage at Enrolment   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
IVA
12
  46.2%
IVB
14
  53.8%
[1]
Measure Description:

Masaoka Staging System:

Stage IVA is pleural or pericardial dissemination. Stage IVB is lymphogenous or hematogenous metastases.

Prior Surgery   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
Radical
11
  42.3%
Debulking
2
   7.7%
[1]
Measure Description: 11 patients had radical surgery including 2 who underwent debulking subsequently.
Prior Radiation  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
7
  26.9%
Prior Neoadjuvant or Adjuvant Chemotherapy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
4
  15.4%
1.Primary Outcome
Title Maximum Tolerated Dose (MTD) of Belinostat
Hide Description The MTD is defined as the highest dose at which less than 2 out of 6 patients experienced a dose limiting toxicity (DLT). A DLT is defined as grade 4 neutropenia lasting more than 7 days despite prophylactic or therapeutic use of granulocyte colony-stimulating factor (G-CSF), febrile neutropenia defined as absolute neutrophil count (ANC) less than 1000/mm(3) and temperature more than 38.5 degrees Celsius or 100.4 degrees Fahrenheit or life threatening sepsis, grade 4 thrombocytopenia or grade 3 thrombocytopenia associated with bleeding during the first cycle of therapy. Any grade 3 or 4 non-hematologic toxicity was considered dose limiting with the following exceptions: grade 3 diarrhea lasting less than 48 hours, grade 3 nausea and/or vomiting lasting less than 48 hours, grade 3 electrolyte abnormalities lasting less than 48 hours, grade 3 creatinine elevation lasting less than 48 hours.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase I Dose Level 1 & Phase I Dose Level 2
Hide Arm/Group Description:

Patients received 250mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Overall Number of Participants Analyzed 8
Measure Type: Number
Unit of Measure: mg/m(2)
1000
2.Primary Outcome
Title Number of Participants With Grade 3 and 4 Dose Limiting Toxicity (DLT) at 2000mg/m(2) Belinostat
Hide Description A DLT is defined as grade 4 neutropenia lasting more than 7 days despite prophylactic or therapeutic use of granulocyte colony-stimulating factor (G-CSF), febrile neutropenia defined as absolute neutrophil count (ANC) less than 1000/mm(3) and temperature more than 38.5 degrees Celsius or 100.4 degrees Fahrenheit or life threatening sepsis, grade 4 thrombocytopenia or grade 3 thrombocytopenia associated with bleeding during the first cycle of therapy. Any grade 3 or 4 non-hematologic toxicity was considered dose limiting with the following exceptions: grade 3 diarrhea lasting less than 48 hours, grade 3 nausea and/or vomiting lasting less than 48 hours, grade 3 electrolyte abnormalities lasting less than 48 hours, grade 3 creatinine elevation lasting less than 48 hours.
Time Frame up to 122 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase I Dose Level 2
Hide Arm/Group Description:

Patients received 500mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Overall Number of Participants Analyzed 2
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 3 Nausea
2
 100.0%
Grade 3 Diarrhea
2
 100.0%
Grade 4 Neutropenia
2
 100.0%
Grade 4 Thrombocytopenia
2
 100.0%
3.Primary Outcome
Title Objective Response Rate (Partial Response (PR) + Complete Response (CR) of Belinostat in Combination With Cisplatin, Doxorubicin and Cyclophosphamide in the First Line Treatment of Patients With Advanced Thymic Malignancies
Hide Description Objective response rate is the number of participants with a best objective response of partial response (PR) + complete response (CR) per the Response Criteria in Solid Tumors (RECIST) divided by the number of participants who had treatment.
Time Frame 43 months
Hide Outcome Measure Data
Hide Analysis Population Description
One patient hospitalized for viral meningoencephalitis during the first cycle was not evaluable for response.
Arm/Group Title Thymic Participants Thymoma Participants Thymic and Thymoma Participants
Hide Arm/Group Description:
The thymic tumors are rare tumors that arise from the thymus and are histologically composed of epithelial cells which are the putative source of malignancy, B and T lymphocytes, interdigitating reticulum cells, macrophages, and myeloid cells. The most common tumors of the thymus are thymomas (well-differentiated neoplasms), atypical thymomas (moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.
The thymic tumors are rare tumors that arise from the thymus and are histologically composed of epithelial cells which are the putative source of malignancy, B and T lymphocytes, interdigitating reticulum cells, macrophages, and myeloid cells. The most common tumors of the thymus are thymomas (well-differentiated neoplasms), atypical thymomas (moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.

All participants who had at least one dose of belinostat. PXD101 (Belinostat) will be given as a 48h continuous intravenous infusion (CIVI) starting on day 1, doxorubicin as a slow intravenous (IV) injection on days 2, 3, cisplatin will be infused over 1 hr on day 2 and cyclophosphamide as a slow IV infusion on Day 3. Treatment will be given every 21 days for no more than 6 cycles or until disease progression. Treatment with PXD101 alone may continue until disease progression.

The thymic tumors are rare tumors that arise from the thymus and are histologically composed of epithelial cells which are the putative source of malignancy, B and T lymphocytes, interdigitating reticulum cells, macrophages, and myeloid cells. The most common tumors of the thymus are thymomas (well-differentiated neoplasms), atypical thymomas (moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.

Overall Number of Participants Analyzed 14 11 25
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
21
(4.7 to 50.8)
64
(30.8 to 89.1)
40
(21.1 to 61.3)
4.Secondary Outcome
Title Number of Participants With Serious and Non-serious Adverse Events
Hide Description Here is the number of participants with serious and non-serious adverse events. For a detailed list of events, see the adverse event module.
Time Frame up to 122 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Participants
Hide Arm/Group Description:

All participants who had at least one dose of belinostat. PXD101 (Belinostat) will be given as a 48h continuous intravenous infusion (CIVI) starting on day 1, doxorubicin as a slow intravenous (IV) injection on days 2, 3, cisplatin will be infused over 1 hr on day 2 and cyclophosphamide as a slow IV infusion on Day 3. Treatment will be given every 21 days for no more than 6 cycles or until disease progression. Treatment with PXD101 alone may continue until disease progression.

The thymic tumors are rare tumors that arise from the thymus and are histologically composed of epithelial cells which are the putative source of malignancy, B and T lymphocytes, interdigitating reticulum cells, macrophages, and myeloid cells. The most common tumors of the thymus are thymomas (well-differentiated neoplasms), atypical thymomas (moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.

Overall Number of Participants Analyzed 26
Measure Type: Count of Participants
Unit of Measure: Participants
Serious
20
  76.9%
Non-serious
26
 100.0%
5.Secondary Outcome
Title Treatment-related Grade 3 and 4 Adverse Events (Highest Grade Per Event Per Patient)
Hide Description Here are the number of patients with treatment -related grade 3 and 4 adverse events (highest grade per event per patient).
Time Frame up to 122 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase I Dose Level 1 + Phase 2 Phase I Dose Level 2 All Participants
Hide Arm/Group Description:

Patients received 250mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD) and was utilized in the expansion phase (phase 2).

Patients received 500mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

All participants who had at least one dose of belinostat.
Overall Number of Participants Analyzed 24 2 26
Measure Type: Count of Participants
Unit of Measure: Participants
Hematologic: Lymphocyte count decreased
24
 100.0%
2
 100.0%
26
 100.0%
Hematologic: White blood cell decreased
22
  91.7%
2
 100.0%
24
  92.3%
Hematologic: Neutrophil count decreased
19
  79.2%
2
 100.0%
21
  80.8%
Hematologic: Platelet count decreased
10
  41.7%
2
 100.0%
12
  46.2%
Hematologic: Anemia
7
  29.2%
2
 100.0%
9
  34.6%
Hepatic and Renal: Hypophosphatemia
4
  16.7%
2
 100.0%
6
  23.1%
Hepatic and Renal: Aspartate aminotransferase incr
4
  16.7%
2
 100.0%
6
  23.1%
Hepatic/Renal: Alanine aminotransferase increased
3
  12.5%
1
  50.0%
4
  15.4%
Hepatic and Renal: Hypokalemia
3
  12.5%
1
  50.0%
4
  15.4%
Hepatic and Renal: Hypermagnesemia
3
  12.5%
0
   0.0%
3
  11.5%
Hepatic and Renal: Hypoalbuminemia
1
   4.2%
1
  50.0%
2
   7.7%
Hepatic and Renal: Hypocalcemia
1
   4.2%
1
  50.0%
2
   7.7%
Hepatic and Renal: Hypomagnesemia
1
   4.2%
0
   0.0%
1
   3.8%
Hepatic and Renal: Hyponatremia
1
   4.2%
0
   0.0%
1
   3.8%
Cardiovascular: Thromboembolic event
3
  12.5%
0
   0.0%
3
  11.5%
Cardiovascular: Atrial fibrillation
0
   0.0%
1
  50.0%
1
   3.8%
Cardiovascular: Ejection fraction decreased
1
   4.2%
0
   0.0%
1
   3.8%
Cardiovascular: Electrocardiogram QTc prolonged
1
   4.2%
0
   0.0%
1
   3.8%
Others: Nausea
1
   4.2%
2
 100.0%
3
  11.5%
Other: Febrile neutropenia
3
  12.5%
0
   0.0%
3
  11.5%
Others: Diarrhea
1
   4.2%
1
  50.0%
2
   7.7%
Others: Lung infection
2
   8.3%
0
   0.0%
2
   7.7%
Otehrs: Entercolitis infectious
1
   4.2%
1
  50.0%
2
   7.7%
Others: Fatigue
2
   8.3%
0
   0.0%
2
   7.7%
Others: Hearing impaired
1
   4.2%
0
   0.0%
1
   3.8%
Others: Hypoxia
1
   4.2%
0
   0.0%
1
   3.8%
Others: Non-cardiac chest pain
1
   4.2%
0
   0.0%
1
   3.8%
Others: Pain in extremity
1
   4.2%
0
   0.0%
1
   3.8%
Others: Syncope
1
   4.2%
0
   0.0%
1
   3.8%
Others: Tumor lysis syndrome
0
   0.0%
1
  50.0%
1
   3.8%
Others: Limb edema
0
   0.0%
1
  50.0%
1
   3.8%
Others: Urinary tract infection
1
   4.2%
0
   0.0%
1
   3.8%
Others: Vomiting
0
   0.0%
1
  50.0%
1
   3.8%
6.Secondary Outcome
Title Clinical Response
Hide Description Response is defined by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time Frame 43 months
Hide Outcome Measure Data
Hide Analysis Population Description
One patient hospitalized for viral meningoencephalitis during the first cycle was not evaluable for response.
Arm/Group Title Thymic Particpants Thymoma Participants Thymic and Thymoma Participants
Hide Arm/Group Description:

PXD101 (Belinostat) will be given as a 48h continuous intravenous infusion (CIVI) starting on day 1, doxorubicin as a slow intravenous (IV) injection on days 2, 3, cisplatin will be infused over 1 hr on day 2 and cyclophosphamide as a slow IV infusion on Day 3. Treatment will be given every 21 days for no more than 6 cycles or until disease progression. Treatment with PXD101 alone may continue until disease progression.

The thymic tumors are rare tumors that arise from the thymus and are histologically composed of epithelial cells which are the putative source of malignancy, B and T lymphocytes, interdigitating reticulum cells, macrophages, and myeloid cells. The most common tumors of the thymus are thymomas (well-differentiated neoplasms), atypical thymomas (moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.

PXD101 (Belinostat) will be given as a 48h continuous intravenous infusion (CIVI) starting on day 1, doxorubicin as a slow intravenous (IV) injection on days 2, 3, cisplatin will be infused over 1 hr on day 2 and cyclophosphamide as a slow IV infusion on Day 3. Treatment will be given every 21 days for no more than 6 cycles or until disease progression. Treatment with PXD101 alone may continue until disease progression.

The thymic tumors are rare tumors that arise from the thymus and are histologically composed of epithelial cells which are the putative source of malignancy, B and T lymphocytes, interdigitating reticulum cells, macrophages, and myeloid cells. The most common tumors of the thymus are thymomas (well-differentiated neoplasms), atypical thymomas (moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.

All participants who had at least one dose of belinostat.

PXD101 (Belinostat) will be given as a 48h continuous intravenous infusion (CIVI) starting on day 1, doxorubicin as a slow intravenous (IV) injection on days 2, 3, cisplatin will be infused over 1 hr on day 2 and cyclophosphamide as a slow IV infusion on Day 3. Treatment will be given every 21 days for no more than 6 cycles or until disease progression. Treatment with PXD101 alone may continue until disease progression.

The thymic tumors are rare tumors that arise from the thymus and are histologically composed of epithelial cells which are the putative source of malignancy, B and T lymphocytes, interdigitating reticulum cells, macrophages, and myeloid cells. The most common tumors of the thymus are thymomas (well-differentiated neoplasms), atypical thymomas (moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.

Overall Number of Participants Analyzed 14 11 25
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response (CR)
0
   0.0%
1
   9.1%
1
   4.0%
Partial Response (PR)
3
  21.4%
6
  54.5%
9
  36.0%
Stable Disease (SD)
10
  71.4%
4
  36.4%
14
  56.0%
Progressive Disease (PD)
1
   7.1%
0
   0.0%
1
   4.0%
7.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description DCR is defined as stable disease (SD) + partial response (PR) + complete response (CR) per the Response Criteria in Solid Tumors (RECIST).
Time Frame 43 months
Hide Outcome Measure Data
Hide Analysis Population Description
One patient hospitalized for viral meningoencephalitis during the first cycle was not evaluable for response.
Arm/Group Title Thymic Participants Thymoma Participants Thymic and Thymoma Participants
Hide Arm/Group Description:

PXD101 (Belinostat) will be given as a 48h continuous intravenous infusion (CIVI) starting on day 1, doxorubicin as a slow intravenous (IV) injection on days 2, 3, cisplatin will be infused over 1 hr on day 2 and cyclophosphamide as a slow IV infusion on Day 3. Treatment will be given every 21 days for no more than 6 cycles or until disease progression. Treatment with PXD101 alone may continue until disease progression.

The thymic tumors are rare tumors that arise from the thymus and are histologically composed of epithelial cells which are the putative source of malignancy, B and T lymphocytes, interdigitating reticulum cells, macrophages, and myeloid cells. The most common tumors of the thymus are thymomas (well-differentiated neoplasms), atypical thymomas (moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.

PXD101 (Belinostat) will be given as a 48h continuous intravenous infusion (CIVI) starting on day 1, doxorubicin as a slow intravenous (IV) injection on days 2, 3, cisplatin will be infused over 1 hr on day 2 and cyclophosphamide as a slow IV infusion on Day 3. Treatment will be given every 21 days for no more than 6 cycles or until disease progression. Treatment with PXD101 alone may continue until disease progression.

The thymic tumors are rare tumors that arise from the thymus and are histologically composed of epithelial cells which are the putative source of malignancy, B and T lymphocytes, interdigitating reticulum cells, macrophages, and myeloid cells. The most common tumors of the thymus are thymomas (well-differentiated neoplasms), atypical thymomas (moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.

All participants who had at least one dose of belinostat. PXD101 (Belinostat) will be given as a 48h continuous intravenous infusion (CIVI) starting on day 1, doxorubicin as a slow intravenous (IV) injection on days 2, 3, cisplatin will be infused over 1 hr on day 2 and cyclophosphamide as a slow IV infusion on Day 3. Treatment will be given every 21 days for no more than 6 cycles or until disease progression. Treatment with PXD101 alone may continue until disease progression.

The thymic tumors are rare tumors that arise from the thymus and are histologically composed of epithelial cells which are the putative source of malignancy, B and T lymphocytes, interdigitating reticulum cells, macrophages, and myeloid cells. The most common tumors of the thymus are thymomas (well-differentiated neoplasms), atypical thymomas (moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.

Overall Number of Participants Analyzed 14 11 25
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
93
(66.1 to 99.8)
100
(71.5 to 100)
96
(79.7 to 99.9)
8.Secondary Outcome
Title Time to Response
Hide Description Time to response is the time between the first day of treatment until first date of response (complete response (CR) + partial response (PR)) (whichever is first recorded).
Time Frame From the first day of treatment until the date of first documented response, assessed up to 43 months
Hide Outcome Measure Data
Hide Analysis Population Description
One patient hospitalized for viral meningoencephalitis during the first cycle was not evaluable for response.
Arm/Group Title Phase I Dose Level 1 & Phase I Dose Level 2
Hide Arm/Group Description:

Patients received 250mg/m(2) or 500mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Overall Number of Participants Analyzed 25
Median (Full Range)
Unit of Measure: days
44.5
(39 to 110)
9.Secondary Outcome
Title Duration of Response
Hide Description Duration of response is measured from the time measurement criteria (e.g. Response Evaluation Criteria in Solid Tumors (RECIST)) are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Time Frame From the time of first response until date of progression, assessed up to 43 months
Hide Outcome Measure Data
Hide Analysis Population Description
One patient hospitalized for viral meningoencephalitis during the first cycle was not evaluable for response. The reason median was not reached is that patients with thymoma have a more indolent disease with a longer survival, therefore a longer duration of response
Arm/Group Title Thymic Participants Thymoma Participants Thymic and Thymoma Participants
Hide Arm/Group Description:

PXD101 (Belinostat) will be given as a 48h continuous intravenous infusion (CIVI) starting on day 1, doxorubicin as a slow intravenous (IV) injection on days 2, 3, cisplatin will be infused over 1 hr on day 2 and cyclophosphamide as a slow IV infusion on Day 3. Treatment will be given every 21 days for no more than 6 cycles or until disease progression. Treatment with PXD101 alone may continue until disease progression.

The thymic tumors are rare tumors that arise from the thymus and are histologically composed of epithelial cells which are the putative source of malignancy, B and T lymphocytes, interdigitating reticulum cells, macrophages, and myeloid cells. The most common tumors of the thymus are thymomas (well-differentiated neoplasms), atypical thymomas (moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.

PXD101 (Belinostat) will be given as a 48h continuous intravenous infusion (CIVI) starting on day 1, doxorubicin as a slow intravenous (IV) injection on days 2, 3, cisplatin will be infused over 1 hr on day 2 and cyclophosphamide as a slow IV infusion on Day 3. Treatment will be given every 21 days for no more than 6 cycles or until disease progression. Treatment with PXD101 alone may continue until disease progression.

The thymic tumors are rare tumors that arise from the thymus and are histologically composed of epithelial cells which are the putative source of malignancy, B and T lymphocytes, interdigitating reticulum cells, macrophages, and myeloid cells. The most common tumors of the thymus are thymomas (well-differentiated neoplasms), atypical thymomas (moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.

All participants who had at least one dose of belinostat. PXD101 (Belinostat) will be given as a 48h continuous intravenous infusion (CIVI) starting on day 1, doxorubicin as a slow intravenous (IV) injection on days 2, 3, cisplatin will be infused over 1 hr on day 2 and cyclophosphamide as a slow IV infusion on Day 3. Treatment will be given every 21 days for no more than 6 cycles or until disease progression. Treatment with PXD101 alone may continue until disease progression.

The thymic tumors are rare tumors that arise from the thymus and are histologically composed of epithelial cells which are the putative source of malignancy, B and T lymphocytes, interdigitating reticulum cells, macrophages, and myeloid cells. The most common tumors of the thymus are thymomas (well-differentiated neoplasms), atypical thymomas (moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.

Overall Number of Participants Analyzed 14 11 25
Median (95% Confidence Interval)
Unit of Measure: months
7.4
(4.2 to 8.5)
NA [1] 
(NA to NA)
7.4 [2] 
(5.2 to NA)
[1]
Median duration of response was not reached for thymoma participants.
[2]
5.2 months to undefined upper limit.
10.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description Duration of time from start of treatment to time of progression or death whichever occurs first.
Time Frame Start of treatment to time of disease progression or death whichever occurs first, assessed up to 43 months
Hide Outcome Measure Data
Hide Analysis Population Description
One patient hospitalized for viral meningoencephalitis during the first cycle was not evaluable. The reason median was not reached is that patients with thymoma have a more indolent disease with a longer survival, therefore a longer duration of response.
Arm/Group Title Thymic Participants Thymoma Participants Thymic and Thymoma Participants
Hide Arm/Group Description:

PXD101 (Belinostat) will be given as a 48h continuous intravenous infusion (CIVI) starting on day 1, doxorubicin as a slow intravenous (IV) injection on days 2, 3, cisplatin will be infused over 1 hr on day 2 and cyclophosphamide as a slow IV infusion on Day 3. Treatment will be given every 21 days for no more than 6 cycles or until disease progression. Treatment with PXD101 alone may continue until disease progression.

The thymic tumors are rare tumors that arise from the thymus and are histologically composed of epithelial cells which are the putative source of malignancy, B and T lymphocytes, interdigitating reticulum cells, macrophages, and myeloid cells. The most common tumors of the thymus are thymomas (well-differentiated neoplasms), atypical thymomas (moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.

PXD101 (Belinostat) will be given as a 48h continuous intravenous infusion (CIVI) starting on day 1, doxorubicin as a slow intravenous (IV) injection on days 2, 3, cisplatin will be infused over 1 hr on day 2 and cyclophosphamide as a slow IV infusion on Day 3. Treatment will be given every 21 days for no more than 6 cycles or until disease progression. Treatment with PXD101 alone may continue until disease progression.

The thymic tumors are rare tumors that arise from the thymus and are histologically composed of epithelial cells which are the putative source of malignancy, B and T lymphocytes, interdigitating reticulum cells, macrophages, and myeloid cells. The most common tumors of the thymus are thymomas (well-differentiated neoplasms), atypical thymomas (moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.

All participants who had at least one dose of belinostat.

PXD101 (Belinostat) will be given as a 48h continuous intravenous infusion (CIVI) starting on day 1, doxorubicin as a slow intravenous (IV) injection on days 2, 3, cisplatin will be infused over 1 hr on day 2 and cyclophosphamide as a slow IV infusion on Day 3. Treatment will be given every 21 days for no more than 6 cycles or until disease progression. Treatment with PXD101 alone may continue until disease progression.

The thymic tumors are rare tumors that arise from the thymus and are histologically composed of epithelial cells which are the putative source of malignancy, B and T lymphocytes, interdigitating reticulum cells, macrophages, and myeloid cells. The most common tumors of the thymus are thymomas (well-differentiated neoplasms), atypical thymomas (moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.

Overall Number of Participants Analyzed 14 11 25
Median (Full Range)
Unit of Measure: months
7.2
(2 to 9)
NA [1] 
(5 to 32)
9
(2 to 32)
[1]
Median PFS was not reached for thymoma participants.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Thymic and Thymoma Participants
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.021
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
11.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival is defined as the on-study date until the date of death or progression as appropriate.
Time Frame Start of treatment to time of death, assessed up to 43 months
Hide Outcome Measure Data
Hide Analysis Population Description
One patient hospitalized for viral meningoencephalitis during the first cycle was not evaluable. The reason median was not reached is that patients with thymoma have a more indolent disease with a longer survival, therefore a longer duration of response.
Arm/Group Title Thymic Participants Thymoma Participants Thymic and Thymoma Participants
Hide Arm/Group Description:

PXD101 (Belinostat) will be given as a 48h continuous intravenous infusion (CIVI) starting on day 1, doxorubicin as a slow intravenous (IV) injection on days 2, 3, cisplatin will be infused over 1 hr on day 2 and cyclophosphamide as a slow IV infusion on Day 3. Treatment will be given every 21 days for no more than 6 cycles or until disease progression. Treatment with PXD101 alone may continue until disease progression.

The thymic tumors are rare tumors that arise from the thymus and are histologically composed of epithelial cells which are the putative source of malignancy, B and T lymphocytes, interdigitating reticulum cells, macrophages, and myeloid cells. The most common tumors of the thymus are thymomas (well-differentiated neoplasms), atypical thymomas (moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.

PXD101 (Belinostat) will be given as a 48h continuous intravenous infusion (CIVI) starting on day 1, doxorubicin as a slow intravenous (IV) injection on days 2, 3, cisplatin will be infused over 1 hr on day 2 and cyclophosphamide as a slow IV infusion on Day 3. Treatment will be given every 21 days for no more than 6 cycles or until disease progression. Treatment with PXD101 alone may continue until disease progression.

The thymic tumors are rare tumors that arise from the thymus and are histologically composed of epithelial cells which are the putative source of malignancy, B and T lymphocytes, interdigitating reticulum cells, macrophages, and myeloid cells. The most common tumors of the thymus are thymomas (well-differentiated neoplasms), atypical thymomas (moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.

All participants who had at least one dose of belinostat. PXD101 (Belinostat) will be given as a 48h continuous intravenous infusion (CIVI) starting on day 1, doxorubicin as a slow intravenous (IV) injection on days 2, 3, cisplatin will be infused over 1 hr on day 2 and cyclophosphamide as a slow IV infusion on Day 3. Treatment will be given every 21 days for no more than 6 cycles or until disease progression. Treatment with PXD101 alone may continue until disease progression.

The thymic tumors are rare tumors that arise from the thymus and are histologically composed of epithelial cells which are the putative source of malignancy, B and T lymphocytes, interdigitating reticulum cells, macrophages, and myeloid cells. The most common tumors of the thymus are thymomas (well-differentiated neoplasms), atypical thymomas (moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.

Overall Number of Participants Analyzed 14 11 25
Median (Full Range)
Unit of Measure: months
21.4
(3 to 37)
NA [1] 
(4 to 43)
28.5
(3 to 43)
[1]
Median OS was not reached for thymoma participants. Thymoma patients with maximum and minimum OS values were alive at the time of data cutoff.
12.Secondary Outcome
Title Time to Half Life (t1/2) of Belinostat
Hide Description Half life is the duration of time for the drug to be reduced to half the original amount.
Time Frame on day 1: pre-belinostat and 0, 0.5, 1 and 2 hours after belinostat infusion, on day 3: 0, 0.8, 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-last belinostat dose.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase 1 Dose Level 1 + Phase 2 Phase 1 Dose Level 2
Hide Arm/Group Description:

Patients received 250mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Patients received 500mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Overall Number of Participants Analyzed 24 1
Mean (Standard Deviation)
Unit of Measure: Hour
0.47  (0.19) 0.40 [1]   (NA)
[1]
One patient was excluded from pharmacokinetic analysis due to insufficient sampling in dose level 2.
13.Secondary Outcome
Title Total Clearance (CL) of Belinostat
Hide Description Clearance is the amount of time for the drug to be eliminated from the body.
Time Frame on day 1: pre-belinostat and 0, 0.5, 1 and 2 hours after belinostat infusion, on day 3: 0, 0.8, 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-last belinostat dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase 1 Dose Level 1 + Phase 2 Phase 1 Dose Level 2
Hide Arm/Group Description:

Patients received 250mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Patients received 500mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Overall Number of Participants Analyzed 24 1
Mean (Standard Deviation)
Unit of Measure: L/hr
133.5  (145.1) 132.1 [1]   (NA)
[1]
One patient was excluded from pharmacokinetic analysis due to insufficient sampling in dose level 2.
14.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Belinostat
Hide Description Plasma concentrations of Belinostat were measured using a newly designed and validated ultra high-performance liquid chromatography (HPLC) with tandem mass spectrometric (MS/MS) assay, with a lower limit of quantification of 5ng/mL.
Time Frame on day 1: pre-belinostat and 0, 0.5, 1 and 2 hours after belinostat infusion, on day 3: 0, 0.8, 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-last belinostat dose
Hide Outcome Measure Data
Hide Analysis Population Description
One patient was excluded from pharmacokinetic analysis due to insufficient sampling in dose level 2. Dose normalized parameters are normalized to absolute total dose (over 48 hours continuous intravenous infusion (CIVI)) for that patient, not dose level.
Arm/Group Title Phase I Dose Level 1 + Phase 2 Phase I Dose Level 2
Hide Arm/Group Description:

Patients received 250mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Patients received 500mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Overall Number of Participants Analyzed 24 1
Mean (Standard Deviation)
Unit of Measure: ng/ml
650.6  (288.1) 1202 [1]   (NA)
[1]
One patient was excluded from pharmacokinetic analysis due to insufficient sampling in dose level 2.
15.Secondary Outcome
Title Maximum Plasma Concentration (Cmax)/Dose
Hide Description Plasma concentrations of Belinostat were measured using a newly designed and validated ultra high-performance liquid chromatography (HPLC) with tandem mass spectrometric (MS/MS) assay, with a lower limit of quantification of 5ng/mL.
Time Frame on day 1: pre-belinostat and 0, 0.5, 1 and 2 hours after belinostat infusion, on day 3: 0, 0.8, 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-last belinostat dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase I Dose Level 1 + Phase 2 Phase I Dose Level 2
Hide Arm/Group Description:

Patients received 250mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Patients received 500mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Overall Number of Participants Analyzed 24 1
Mean (Standard Deviation)
Unit of Measure: ng/ml/mg
0.36  (0.21) 0.31 [1]   (NA)
[1]
One patient was excluded from pharmacokinetic analysis due to insufficient sampling in dose level 2.
16.Secondary Outcome
Title Time to Maximum Plasma Concentration (Tmax)
Hide Description Time to reach peak concentration after drug administration.
Time Frame on day 1: pre-belinostat and 0, 0.5, 1 and 2 hours after belinostat infusion, on day 3: 0, 0.8, 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-last belinostat dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase I Dose Level 1 + Phase 2 Phase I Dose Level 2
Hide Arm/Group Description:

Patients received 250mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Patients received 500mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Overall Number of Participants Analyzed 24 1
Mean (Standard Deviation)
Unit of Measure: Hour
25.28  (22.29) 50.0 [1]   (NA)
[1]
One patient was excluded from pharmacokinetic analysis due to insufficient sampling in dose level 2.
17.Secondary Outcome
Title Area Under the Plasma Concentration vs. Time Curve Extrapolated to Infinity (AUC(INF))
Hide Description AUC is a measure of the serum concentration of Belinostat over time. It is used to characterize drug absorption.
Time Frame on day 1: pre-belinostat and 0, 0.5, 1 and 2 hours after belinostat infusion, on day 3: 0, 0.8, 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-last belinostat dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase I Dose Level 1 + Phase 2 Phase I Dose Level 2
Hide Arm/Group Description:

Patients received 250mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Patients received 500mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Overall Number of Participants Analyzed 24 1
Mean (Standard Deviation)
Unit of Measure: hr*ng/ml
19756  (7634) 29686 [1]   (NA)
[1]
One patient was excluded from pharmacokinetic analysis due to insufficient sampling in dose level 2.
18.Secondary Outcome
Title Area Under the Plasma Concentration vs. Time Curve Extrapolated to Infinity (AUC(INF)/Dose
Hide Description AUC is a measure of the serum concentration of Belinostat over time. It is used to characterize drug absorption.
Time Frame on day 1: pre-belinostat and 0, 0.5, 1 and 2 hours after belinostat infusion, on day 3: 0, 0.8, 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-last belinostat dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase I Dose Level 1 + Phase 2 Phase I Dose Level 2
Hide Arm/Group Description:

Patients received 250mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Patients received 500mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Overall Number of Participants Analyzed 24 1
Mean (Standard Deviation)
Unit of Measure: hr*ng/ml/mg
10.78  (5.57) 7.57 [1]   (NA)
[1]
One patient was excluded from pharmacokinetic analysis due to insufficient sampling in dose level 2.
19.Secondary Outcome
Title Relative Change Observed in Total Protein Hyperacetylation of Cluster of Differentiation 3 (CD3)+T Cells With Belinostat
Hide Description Changes in marker levels from baseline. All pre values were set to 1 so that we could measure changes relative to the baseline.
Time Frame Baseline Cycle 1 Day 1 (C1D1), Cycle 1 Day 2 (C1D2), Cycle 1 Day 3 (C1D3), and Cycle 2 Day 1 (C2D1)
Hide Outcome Measure Data
Hide Analysis Population Description
One patient hospitalized for viral meningoencephalitis during the first cycle was not evaluable. Two samples could not be analyzed since they were of poor quality with too few cells for immune cell subset analysis or the samples could not be collected in time for pharmacodynamics analysis.
Arm/Group Title All Participants
Hide Arm/Group Description:

Patients received 250mg/m(2) or 500mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Overall Number of Participants Analyzed 23
Median (Full Range)
Unit of Measure: Relative fold change
C1D2
3.45
(0.96 to 14.29)
C1D3
2.49
(0.98 to 10.74)
C2D1
1.15
(0.97 to 2.40)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All Participants
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.30
Comments Fold change at Cycle 2 Day 1 vs. pre was assessed. Only differences with p<0.005 could be potentially considered statistically significant while those with 0.005<p<0.05 would represent trends towards a difference.
Method Wilcoxon signed rank test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection All Participants
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments Fold change at Cycle 1 Day 2 vs. pre was assessed. p values calculated were done using a Wilcoxon signed rank test relative to a ratio of 1.
Method Wilcoxon signed rank test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection All Participants
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments Fold change at Cycle 1 Day 3 vs. pre was assessed. p values calculated were done using a Wilcoxon signed rank test relative to a ratio of 1.
Method Wilcoxon signed rank test
Comments [Not Specified]
20.Secondary Outcome
Title Relative Changes in the Number of Tregs With Treatment
Hide Description Changes in marker levels from baseline. All pre values were set to 1 so that we could measure changes relative to the baseline.
Time Frame Baseline Cycle 1 Day 1 (C1D1), Cycle 1 Day 2 (C1D2), Cycle 1 Day 3 (C1D3), and Cycle 2 Day 1 (C2D1)
Hide Outcome Measure Data
Hide Analysis Population Description
One patient hospitalized for viral meningoencephalitis during the first cycle was not evaluable. Three samples could not be analyzed since they were of poor quality with too few cells for immune cell subset analysis or the samples could not be collected in time for pharmacodynamics analysis.
Arm/Group Title All Participants
Hide Arm/Group Description:

Patients received 250mg/m(2) or 500mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Overall Number of Participants Analyzed 22
Median (Full Range)
Unit of Measure: relative fold change
C1D2
0.58
(0.03 to 1.88)
C1D3
0.47
(0 to 1.58)
C2D1
1.12
(0.12 to 2.55)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All Participants
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.76
Comments Fold change at Cycle 2 Day 1 vs. pre was assessed.Only differences with p<0.005 could be potentially considered statistically significant while those with 0.005<p<0.05 would represent trends towards a difference.
Method Wilcoxon signed rank test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection All Participants
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments Fold change at Cycle 1 Day 2 vs. pre was assessed. p values calculated were done using a Wilcoxon signed rank test relative to a ratio of 1.
Method Wilcoxon signed rank test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection All Participants
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments Fold change at Cycle 1 Day 3 vs. pre was assessed. p values calculated were done using a Wilcoxon signed rank test relative to a ratio of 1.
Method Wilcoxon signed rank test
Comments [Not Specified]
21.Secondary Outcome
Title Relative Changes in T Cell Immunoglobulin Domain and Mucin Domain-3 (TIM3)-Expressing Cluster of Differentiation 8 (CD8)+Tcells
Hide Description Changes in marker levels from baseline. All pre values were set to 1 so that we could measure changes relative to the baseline.
Time Frame Baseline Cycle 1 Day 1 (C1D1), Cycle 1 Day 2 (C1D2), Cycle 1 Day 3 (C1D3), and Cycle 2 Day 1 (C2D1)
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Hide Analysis Population Description
One patient hospitalized for viral meningoencephalitis during the first cycle was not evaluable. Three samples could not be analyzed since they were of poor quality with too few cells for immune cell subset analysis or the samples could not be collected in time for pharmacodynamics analysis.
Arm/Group Title All Participants
Hide Arm/Group Description:

Patients received 250mg/m(2) or 500mg/m(2) of belinostat via four consecutive 12 hour continuous intravenous infusion (CIVI) for 48 hours starting on day 1. At dose levels 1 and 2, patients received the same doses of doxorubicin (25mg/m(2) on days 2 and 3, intravenous push over 3-5 minutes), cisplatin (50 mg/m(2) over 60 minutes intravenous on day 2 after doxorubicin), and cyclophosphamide (500mg/m(2) over 60 minutes intravenous on day 3 after doxorubicin). Combination of chemotherapy and belinostat was repeated every 21 days for a total of 6 cycles unless there was evidence of disease progression or intolerance of the study treatment.

A conventional 3 + 3 dose escalation design was used to determine maximum tolerated dose (MTD).

Overall Number of Participants Analyzed 22
Median (Full Range)
Unit of Measure: Relative fold change
C1D2
0.81
(0.57 to 1.25)
C1D3
0.66
(0.42 to 0.91)
C2D1
1.01
(0.67 to 1.31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All Participants
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.95
Comments Fold change at Cycle 2 Day 1 vs. pre was assessed. p values calculated were done using a Wilcoxon signed rank test relative to a ratio of 1.
Method Wilcoxon signed rank test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection All Participants
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments Fold change at Cycle 1 Day 2 vs. pre was assessed. p values calculated were done using a Wilcoxon signed rank test relative to a ratio of 1.
Method Wilcoxon signed rank test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection All Participants
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments Fold change at Cycle 1 Day 3 vs. pre was assessed. p values calculated were done using a Wilcoxon signed rank test relative to a ratio of 1.
Method Wilcoxon signed rank test
Comments [Not Specified]
Time Frame up to 122 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title All Participants
Hide Arm/Group Description All participants who had at least one dose of belinostat.
All-Cause Mortality
All Participants
Affected / at Risk (%)
Total   13/26 (50.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
All Participants
Affected / at Risk (%) # Events
Total   20/26 (76.92%)    
Blood and lymphatic system disorders   
Anemia  1  1/26 (3.85%)  1
Febrile neutropenia  1  1/26 (3.85%)  1
Cardiac disorders   
Atrial fibrillation  1  1/26 (3.85%)  1
Gastrointestinal disorders   
Diarrhea  1  1/26 (3.85%)  1
General disorders   
Death NOS  1  11/26 (42.31%)  11
Infusion related reaction  1  1/26 (3.85%)  1
Localized edema  1  1/26 (3.85%)  1
Infections and infestations   
Catheter related infection  1  2/26 (7.69%)  2
Infections and infestations - Other, Meningoencephylitis  1  1/26 (3.85%)  1
Infections and infestations - Other, West Nile virus  1  1/26 (3.85%)  1
Lung infection  1  1/26 (3.85%)  1
Investigations   
Electrocardiogram QT corrected interval prolonged  1  1/26 (3.85%)  1
Neutrophil count decreased  1  1/26 (3.85%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other,Basal cell carcinoma  1  1/26 (3.85%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Death  1  2/26 (7.69%)  2
Respiratory, thoracic and mediastinal disorders   
Respiratory failure  1  1/26 (3.85%)  1
Vascular disorders   
Thromboembolic event  1  5/26 (19.23%)  5
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
All Participants
Affected / at Risk (%) # Events
Total   26/26 (100.00%)    
Blood and lymphatic system disorders   
Anemia  1  23/26 (88.46%)  124
Cardiac disorders   
Atrial fibrillation  1  1/26 (3.85%)  1
Pericardial effusion  1  1/26 (3.85%)  1
Sinus bradycardia  1  3/26 (11.54%)  6
Sinus tachycardia  1  2/26 (7.69%)  4
Ear and labyrinth disorders   
Hearing impaired  1  2/26 (7.69%)  3
Otitis media  1  1/26 (3.85%)  1
Tinnitus  1  2/26 (7.69%)  2
Eye disorders   
Blurred vision  1  1/26 (3.85%)  1
Floaters  1  1/26 (3.85%)  1
Watering eyes  1  1/26 (3.85%)  1
Gastrointestinal disorders   
Constipation  1  6/26 (23.08%)  10
Diarrhea  1  9/26 (34.62%)  18
Dry mouth  1  1/26 (3.85%)  1
Dyspepsia  1  2/26 (7.69%)  3
Dysphagia  1  2/26 (7.69%)  2
Enterocolitis infectious  1  3/26 (11.54%)  3
Gastritis  1  1/26 (3.85%)  1
Gastroesophageal reflux disease  1  1/26 (3.85%)  1
Mucositis oral  1  7/26 (26.92%)  8
Nausea  1  16/26 (61.54%)  21
Oral pain  1  1/26 (3.85%)  1
Vomiting  1  6/26 (23.08%)  10
General disorders   
Chills  1  3/26 (11.54%)  3
Edema limbs  1  4/26 (15.38%)  5
Fatigue  1  15/26 (57.69%)  28
Fever  1  3/26 (11.54%)  3
Non-cardiac chest pain  1  1/26 (3.85%)  1
Pain  1  2/26 (7.69%)  4
Infections and infestations   
Catheter related infection  1  1/26 (3.85%)  1
Infections and infestations - Other, folliculitis, axilla right  1  1/26 (3.85%)  1
Infections and infestations - Other, Pseudomonas bacteremia  1  1/26 (3.85%)  1
Laryngitis  1  1/26 (3.85%)  1
Lung infection  1  3/26 (11.54%)  3
Mucosal infection  1  1/26 (3.85%)  1
Paronychia  1  1/26 (3.85%)  1
Pharyngitis  1  3/26 (11.54%)  4
Sinusitis  1  3/26 (11.54%)  3
Upper respiratory infection  1  2/26 (7.69%)  3
Injury, poisoning and procedural complications   
Bruising  1  1/26 (3.85%)  1
Fall  1  1/26 (3.85%)  1
Investigations   
Activated partial thromboplastin time prolonged  1  3/26 (11.54%)  6
Alanine aminotransferase increased  1  10/26 (38.46%)  26
Alkaline phosphatase increased  1  1/26 (3.85%)  1
Aspartate aminotransferase increased  1  10/26 (38.46%)  25
Creatinine increased  1  4/26 (15.38%)  12
Ejection fraction decreased  1  2/26 (7.69%)  2
Electrocardiogram QT corrected interval prolonged  1  8/26 (30.77%)  27
Lymphocyte count decreased  1  26/26 (100.00%)  294
Neutrophil count decreased  1  24/26 (92.31%)  112
Platelet count decreased  1  17/26 (65.38%)  82
Weight loss  1  1/26 (3.85%)  1
White blood cell decreased  1  26/26 (100.00%)  161
Metabolism and nutrition disorders   
Anorexia  1  15/26 (57.69%)  18
Dehydration  1  1/26 (3.85%)  1
Hypercalcemia  1  2/26 (7.69%)  2
Hyperglycemia  1  4/26 (15.38%)  4
Hyperkalemia  1  1/26 (3.85%)  1
Hypermagnesemia  1  3/26 (11.54%)  7
Hypoalbuminemia  1  19/26 (73.08%)  66
Hypocalcemia  1  19/26 (73.08%)  58
Hypokalemia  1  7/26 (26.92%)  13
Hypomagnesemia  1  5/26 (19.23%)  14
Hyponatremia  1  3/26 (11.54%)  8
Hypophosphatemia  1  12/26 (46.15%)  34
Tumor lysis syndrome  1  1/26 (3.85%)  1
Musculoskeletal and connective tissue disorders   
Arthralgia  1  2/26 (7.69%)  3
Muscle weakness left-sided  1  1/26 (3.85%)  1
Muscle weakness lower limb  1  2/26 (7.69%)  2
Myalgia  1  1/26 (3.85%)  1
Pain in extremity  1  4/26 (15.38%)  6
Nervous system disorders   
Concentration impairment  1  2/26 (7.69%)  2
Dizziness  1  2/26 (7.69%)  3
Dysgeusia  1  7/26 (26.92%)  9
Headache  1  5/26 (19.23%)  7
Peripheral sensory neuropathy  1  7/26 (26.92%)  7
Presyncope  1  1/26 (3.85%)  1
Syncope  1  1/26 (3.85%)  2
Psychiatric disorders   
Agitation  1  1/26 (3.85%)  1
Anxiety  1  1/26 (3.85%)  1
Depression  1  3/26 (11.54%)  3
Insomnia  1  4/26 (15.38%)  4
Renal and urinary disorders   
Hematuria  1  1/26 (3.85%)  1
Urinary incontinence  1  1/26 (3.85%)  1
Urinary tract infection  1  3/26 (11.54%)  5
Urinary tract pain  1  1/26 (3.85%)  1
Respiratory, thoracic and mediastinal disorders   
Cough  1  6/26 (23.08%)  10
Dyspnea  1  5/26 (19.23%)  6
Epistaxis  1  2/26 (7.69%)  2
Hiccups  1  2/26 (7.69%)  2
Hoarseness  1  1/26 (3.85%)  1
Hypoxia  1  2/26 (7.69%)  3
Nasal congestion  1  2/26 (7.69%)  3
Pneumonitis  1  1/26 (3.85%)  1
Postnasal drip  1  2/26 (7.69%)  3
Sore throat  1  1/26 (3.85%)  1
Skin and subcutaneous tissue disorders   
Alopecia  1  7/26 (26.92%)  7
Erythema multiforme  1  1/26 (3.85%)  1
Hyperhidrosis  1  1/26 (3.85%)  1
Nail discoloration  1  2/26 (7.69%)  2
Palmar-plantar erythrodysesthesia syndrome  1  1/26 (3.85%)  1
Rash maculo-papular  1  1/26 (3.85%)  1
Skin and subcutaneous tissue disorders - Other, Basal Cell Carcinoma per biopsy  1  1/26 (3.85%)  1
Skin and subcutaneous tissue disorders - Other, Ecchymotic nod L arm  1  1/26 (3.85%)  1
Skin and subcutaneous tissue disorders - Other, skin lesion  1  1/26 (3.85%)  1
Skin hyperpigmentation  1  2/26 (7.69%)  3
Skin hypopigmentation  1  1/26 (3.85%)  1
Skin ulceration  1  1/26 (3.85%)  1
Vascular disorders   
Hypertension  1  3/26 (11.54%)  52
Hypotension  1  1/26 (3.85%)  1
Superficial thrombophlebitis  1  1/26 (3.85%)  1
Thromboembolic event  1  5/26 (19.23%)  5
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Arun Rajan
Organization: National Cancer Institute
Phone: 301-594-5322
EMail: rajana@mail.nih.gov
Layout table for additonal information
Responsible Party: Arun Rajan, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT01100944     History of Changes
Other Study ID Numbers: 100077
10-C-0077
First Submitted: March 18, 2010
First Posted: April 9, 2010
Results First Submitted: July 26, 2016
Results First Posted: November 15, 2016
Last Update Posted: August 10, 2017