Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 41 of 42 for:    Malignant Hyperthermia 5

Combination of Decitabine and Temozolomide in the Treatment of Patients With Metastatic Melanoma (UPCI-07-008)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00715793
Recruitment Status : Completed
First Posted : July 15, 2008
Results First Posted : October 3, 2017
Last Update Posted : October 3, 2017
Sponsor:
Collaborators:
Eisai Inc.
Schering-Plough
Information provided by (Responsible Party):
Hussein Tawbi, University of Pittsburgh

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Malignant Melanoma
Interventions Drug: Decitabine
Drug: Temozolomide
Procedure: biopsy
Enrollment 39
Recruitment Details  
Pre-assignment Details  
Arm/Group Title DAC (Decitabine) 0.075 mg/kg + TMZ (Temozolomide) DAC (Decitabine) 0.15 mg/kg + TMZ (Temozolomide)
Hide Arm/Group Description Patients with non-resectable stage IIIB/C or stage IV metastatic melanoma with either no prior therapy or have progressed despite prior therapies, who were treated with DAC 0.075 mg/kg intravenously daily × 5 days/week for 2 weeks, TMZ orally 75 mg/m^2 qd for weeks 2–5 of a 6-week cycle. Patients with non-resectable stage IIIB/C or stage IV metastatic melanoma with either no prior therapy or have progressed despite prior therapies, who were treated with DAC 0.15 mg/kg intravenously daily × 5 days/week for 2 weeks, TMZ orally 75 mg/m^2 qd for weeks 2–5 of a 6-week cycle.
Period Title: Phase 1 RP2D DAC + TMZ
Started 4 6
Completed 3 6
Not Completed 1 0
Reason Not Completed
secondary disease in Cycle 1             1             0
Period Title: Phase 2 DAC (0.15 mg/kg) + TMZ
Started 0 29
Completed 0 27
Not Completed 0 2
Reason Not Completed
not assessable for tumor response             0             2
Arm/Group Title All Study Participants DAC (Decitabine) + TMZ (Temozolomide)
Hide Arm/Group Description Patients with non-resectable stage IIIB/C or stage IV metastatic melanoma with either no prior therapy, or, have progressed despite prior therapies, who were treated with DAC 0.15 mg/kg intravenously daily × 5 days/week for 2 weeks + TMZ orally 75 mg/m^2 qd for weeks 2–5 of a 6-week cycle).
Overall Number of Baseline Participants 39
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 39 participants
63.3
(36.2 to 77.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 39 participants
Female
12
  30.8%
Male
27
  69.2%
1.Primary Outcome
Title Percentage of Participants That Experienced a Dose Limiting Toxicity (DLT)
Hide Description Dose-limiting toxicities (DLTs) were defined as grade 4 neutropenia or thrombocytopenia which lasts >7 days; grade 3 or 4 febrile neutropenia; grade 3 or greater non-hematological toxic effects.
Time Frame Up to 26 months
Hide Outcome Measure Data
Hide Analysis Population Description
Patients participating in the Phase 1 portion of the study that were treated on a standard “3+3” phase I dose-escalation design who were observed for unacceptable toxicities.
Arm/Group Title Dose Level 1:DAC (Decitabine) 0.075 mg/kg + TMZ (Temozolomide) Dose Level 2:DAC (Decitabine) 0.15 mg/kg + TMZ (Temozolomide)
Hide Arm/Group Description:
Patients with non-resectable stage IIIB/C or stage IV metastatic melanoma with either no prior therapy or have progressed despite prior therapies, who were treated with DAC 0.075 mg/kg intravenously daily × 5 days/week for 2 weeks, TMZ orally 75 mg/m^2 qd for weeks 2–5 of a 6-week cycle.
Patients with non-resectable stage IIIB/C or stage IV metastatic melanoma with either no prior therapy or have progressed despite prior therapies, who were treated with DAC 0.15 mg/kg intravenously daily × 5 days/week for 2 weeks, TMZ orally 75 mg/m^2 qd for weeks 2–5 of a 6-week cycle.
Overall Number of Participants Analyzed 2 6
Measure Type: Number
Unit of Measure: percentage of participants
0 17
2.Primary Outcome
Title Overall Response Rate (ORR)
Hide Description Using RECIST v1.0 criteria, overall response rate (ORR) was determined by the number of participants with complete response (CR) + the number of participants with partial response (PR) / the number of participants with complete response (CR) + the number of participants with partial response (PR) + the number of participants with stable disease (SD) + the number of participants with progressive disease (PD), multiplied by 100. Per RECIST v1.0 criteria (assessed by MRI or CT): Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response (PR) nor sufficient increase to to qualify for Progressive Disease (PD); PD, 20% increase in the sum if target lesion or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions.
Time Frame Up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DAC (Decitabine) + TMZ (Temozolomide)
Hide Arm/Group Description:
Patients with non-resectable stage IIIB/C or stage IV metastatic melanoma with either no prior therapy or have progressed despite prior therapies, who were treated with Intravenous DAC of 0.15 mg/kg daily for 5 days a week for the first 2 weeks of a 6-week cycle who received TMZ orally at 75 mg/m^2 daily for 4 weeks (weeks 2–5) of a 6-week cycle.
Overall Number of Participants Analyzed 33
Measure Type: Number
Unit of Measure: percentage of participants
18
3.Primary Outcome
Title Recommended Phase 2 Dose (RP2D) of DAC + TMZ
Hide Description Toxicity assessments used CTCAE v3.0. Two dose levels were explored in the phase I portion of the study. A modified 3 + 3 ‘up and down’ design was used. Given the knowledge that DAC exhibits its epigenetic effects at 30-fold lower doses than at its maximum-tolerated dose (MTD), escalation of DAC to the MTD was not done.
Time Frame Up to 26 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Single Arm
Hide Arm/Group Description:

Decitabine: In Part I patients will be treated on a standard "3+3" phase I dose-escalation design starting at 0.075 mg/kg until a decitabine dose level of 0.15 mg/kg is reached, or, in case unacceptable toxicities are observed, at the maximum tolerated dose (Phase II recommended dose). Decitabine will be administered at the specified dose level, intravenously, daily 5 days a week for the first 2 weeks of a 6-week cycle.

Temozolomide: Temozolomide is available in 25 mg and 100 mg tablets that will be administered orally; doses will be rounded to the nearest 25 mg. Temozolomide will be administered orally at 75 mg/m2 daily for 4 weeks starting on week 2 of a 6-week cycle.

biopsy: Fine needle aspirates (FNA) and/or core biopsies of tumor samples will be obtained from consenting patients with accessible, evaluable disease, on days 1, 8, 15, and 29 of the first cycle and when patients go off study. Biopsies are optional in Phase I and required for all consenting subjects in Phase II.

Overall Number of Participants Analyzed 8
Measure Type: Number
Unit of Measure: mg/kg DAC
0.15
4.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description Using RECIST v1.0 criteria, disease control rate (DCR) was determined by the number of participants with complete response (CR) + the number of participants with partial response (PR) + the number of participants with stable disease (SD) / the number of participants with complete response (CR) + the number of participants with partial response (PR) + the number of participants with stable disease (SD) + the number of participants with progressive disease (PD). Per RECIST v1.0 criteria (assessed by MRI or CT): Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response (PR) nor sufficient increase to to qualify for Progressive Disease (PD); PD, 20% increase in the sum if target lesion or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions.
Time Frame Up to 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DAC (Decitabine) + TMZ (Temozolomide)
Hide Arm/Group Description:
Patients with non-resectable stage IIIB/C or stage IV metastatic melanoma with either no prior therapy or have progressed despite prior therapies, who were treated with Intravenous DAC of 0.15 mg/kg daily for 5 days a week for the first 2 weeks of a 6-week cycle who received TMZ orally at 75 mg/m^2 daily for 4 weeks (weeks 2–5) of a 6-week cycle.
Overall Number of Participants Analyzed 33
Measure Type: Number
Unit of Measure: percentage of participants
61
5.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description PFS was defined as the time from study entry until the documented radiological or symptomatic progression. Per RECIST v1.0 criteria (assessed by MRI or CT): Progressive Disease (PD); PD, 20% increase in the sum if target lesion or the appearance of new lesions.
Time Frame Up to 42 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DAC (Decitabine) + TMZ (Temozolomide)
Hide Arm/Group Description:
Patients with non-resectable stage IIIB/C or stage IV metastatic melanoma with either no prior therapy or have progressed despite prior therapies, who were treated with Intravenous DAC of 0.15 mg/kg daily for 5 days a week for the first 2 weeks of a 6-week cycle who received TMZ orally at 75 mg/m^2 daily for 4 weeks (weeks 2–5) of a 6-week cycle.
Overall Number of Participants Analyzed 33
Median (Full Range)
Unit of Measure: months
3.4
(1.0 to 20.4)
6.Secondary Outcome
Title 6-month Progression-free Survival (PFS) Rate
Hide Description [Not Specified]
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Patients that either progressed or died by 6 months.
Arm/Group Title DAC (Decitabine) + TMZ (Temozolomide)
Hide Arm/Group Description:
Patients with non-resectable stage IIIB/C or stage IV metastatic melanoma with either no prior therapy or have progressed despite prior therapies, who were treated with Intravenous DAC of 0.15 mg/kg daily for 5 days a week for the first 2 weeks of a 6-week cycle who received TMZ orally at 75 mg/m^2 daily for 4 weeks (weeks 2–5) of a 6-week cycle.
Overall Number of Participants Analyzed 33
Measure Type: Number
Unit of Measure: percentage of participants
32.4
7.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from study entry until the death or date of last contract.
Time Frame Up to 42 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DAC (Decitabine) + TMZ (Temozolomide)
Hide Arm/Group Description:
Patients with non-resectable stage IIIB/C or stage IV metastatic melanoma with either no prior therapy or have progressed despite prior therapies, who were treated with Intravenous DAC of 0.15 mg/kg daily for 5 days a week for the first 2 weeks of a 6-week cycle who received TMZ orally at 75 mg/m^2 daily for 4 weeks (weeks 2–5) of a 6-week cycle.
Overall Number of Participants Analyzed 33
Median (95% Confidence Interval)
Unit of Measure: months
12.4
(10.4 to 20.4)
8.Secondary Outcome
Title 1-year Overall Survival (OS) Rate
Hide Description Percentage of patients alive at one year (number of patients alive / total number of evaluable (analyzed) patients).
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DAC (Decitabine) + TMZ (Temozolomide)
Hide Arm/Group Description:
Patients with non-resectable stage IIIB/C or stage IV metastatic melanoma with either no prior therapy or have progressed despite prior therapies, who were treated with Intravenous DAC of 0.15 mg/kg daily for 5 days a week for the first 2 weeks of a 6-week cycle who received TMZ orally at 75 mg/m^2 daily for 4 weeks (weeks 2–5) of a 6-week cycle.
Overall Number of Participants Analyzed 33
Measure Type: Number
Unit of Measure: percentage of participants
56
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title DAC (Decitabine) + TMZ (Temozolomide)
Hide Arm/Group Description Comprehensive listing of adverse events are presented in total (includes events from both Phase 1 and and Phase 2 of study).
All-Cause Mortality
DAC (Decitabine) + TMZ (Temozolomide)
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
DAC (Decitabine) + TMZ (Temozolomide)
Affected / at Risk (%)
Total   7/39 (17.95%) 
General disorders   
Pain, Abdomen NOS   2/39 (5.13%) 
Pain, Back   1/39 (2.56%) 
Infections and infestations   
Febrile neutropenia   3/39 (7.69%) 
Nervous system disorders   
Neuropathy: motor   1/39 (2.56%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnea (shortness of breath)   2/39 (5.13%) 
Hypoxia   1/39 (2.56%) 
Vascular disorders   
Peripheral arterial ischemia   1/39 (2.56%) 
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 5%
DAC (Decitabine) + TMZ (Temozolomide)
Affected / at Risk (%)
Total   39/39 (100.00%) 
Blood and lymphatic system disorders   
Edema: limb   10/39 (25.64%) 
Hemoglobin   8/39 (20.51%) 
Hemorrhage/Bleeding - Other (Specify, __)   3/39 (7.69%) 
Leukocytes (total WBC)   31/39 (79.49%) 
Neutrophils/granulocytes (ANC/AGC)   32/39 (82.05%) 
Platelets   6/39 (15.38%) 
Cardiac disorders   
Hypertension   6/39 (15.38%) 
Gastrointestinal disorders   
Constipation   25/39 (64.10%) 
Diarrhea   10/39 (25.64%) 
Heartburn/dyspepsia   5/39 (12.82%) 
Mucositis/stomatitis (clinical exam), Oral cavity   7/39 (17.95%) 
Nausea   31/39 (79.49%) 
Taste alteration (dysgeusia)   5/39 (12.82%) 
Vomiting   8/39 (20.51%) 
General disorders   
Anorexia   15/39 (38.46%) 
Fatigue (asthenia, lethargy, malaise)   35/39 (89.74%) 
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)   5/39 (12.82%) 
Insomnia   8/39 (20.51%) 
Pain, Abdomen NOS   14/39 (35.90%) 
Pain, Back   11/39 (28.21%) 
Pain, Chest wall   3/39 (7.69%) 
Pain, Extremity-limb   11/39 (28.21%) 
Pain, Head/headache   17/39 (43.59%) 
Pain, Joint   6/39 (15.38%) 
Weight loss   3/39 (7.69%) 
Immune system disorders   
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)   5/39 (12.82%) 
Infections and infestations   
Infection with normal ANC or Grade 1 or 2 neutrophils, Skin (cellulitis)   4/39 (10.26%) 
Infection with normal ANC or Grade 1 or 2 neutrophils, Upper airway NOS   3/39 (7.69%) 
Metabolism and nutrition disorders   
Albumin, serum-low (hypoalbuminemia)   6/39 (15.38%) 
Metabolic/Laboratory - Other (Specify, __)   7/39 (17.95%) 
Phosphate, serum-low (hypophosphatemia)   4/39 (10.26%) 
Nervous system disorders   
Confusion   3/39 (7.69%) 
Dizziness   6/39 (15.38%) 
Mood alteration, Anxiety   11/39 (28.21%) 
Mood alteration, Depression   8/39 (20.51%) 
Neuropathy: sensory   9/39 (23.08%) 
Respiratory, thoracic and mediastinal disorders   
Cough   12/39 (30.77%) 
Dyspnea (shortness of breath)   9/39 (23.08%) 
Skin and subcutaneous tissue disorders   
Pruritus/itching   8/39 (20.51%) 
Rash/desquamation   5/39 (12.82%) 
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Hussein Tawbi, MD, PhD
Organization: University of Pittsburgh
Phone: 713-792-6111
EMail: HTawbi@mdanderson.org
Layout table for additonal information
Responsible Party: Hussein Tawbi, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00715793     History of Changes
Other Study ID Numbers: UPCI 07-008
First Submitted: June 27, 2008
First Posted: July 15, 2008
Results First Submitted: July 29, 2016
Results First Posted: October 3, 2017
Last Update Posted: October 3, 2017