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Trial record 43 of 228 for:    "Anaplastic oligodendroglioma"

FR901228 in Treating Patients With Recurrent High-Grade Gliomas

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ClinicalTrials.gov Identifier: NCT00085540
Recruitment Status : Completed
First Posted : June 11, 2004
Results First Posted : November 15, 2016
Last Update Posted : January 2, 2017
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Adult Anaplastic Astrocytoma
Adult Anaplastic Oligodendroglioma
Adult Giant Cell Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Intervention Drug: depsipeptide
Enrollment 50

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Phase 1 Dose Escalation - Romidepsin Phase 2 Dose From Phase 1 - Romidepsin
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Patients receive FR901228 (romidepsin) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Dose escalation two dose levels:

Romidepsin (depsipeptide): 13.3mg/m2 and 17.7mg/m2

Pharmacokinetics

depsipeptide: Given IV

Patients receive FR901228 (romidepsin) as in phase I at dose level 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity

Romidepsin (depsipeptide): 13.3mg/m2

depsipeptide: Given IV

Period Title: Overall Study
Started 8 42
Completed 8 40
Not Completed 0 2
Reason Not Completed
Withdrawal by Subject             0             1
Protocol Violation             0             1
Arm/Group Title Phase 1 Dose Escalation - Romidepsin Phase 2 Dose From Phase 1 - Romidepsin Total
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Patients receive FR901228 (romidepsin) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Dose escalation two dose levels:

Romidepsin (depsipeptide): 13.3mg/m2 and 17.7mg/m2

Pharmacokinetics

depsipeptide: Given IV

Patients receive FR901228 (romidepsin) as in phase I at dose level 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity

Romidepsin (depsipeptide): 13.3mg/m2

depsipeptide: Given IV

Total of all reporting groups
Overall Number of Baseline Participants 8 40 48
Hide Baseline Analysis Population Description
two patients were removed from the analysis due to one withdrawing consent and one was deemed ineligible.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 8 participants 40 participants 48 participants
52
(44 to 57)
55
(37 to 79)
54
(37 to 79)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 40 participants 48 participants
Female
3
  37.5%
10
  25.0%
13
  27.1%
Male
5
  62.5%
30
  75.0%
35
  72.9%
Karnofsky Performance Status Scale (KPS)   [1] 
Measure Type: Number
Unit of measure:  Units on a scale
Number Analyzed 8 participants 40 participants 48 participants
90-100 4 19 23
60-80 4 21 25
[1]
Measure Description: Higher score better 100 normal no complaints/disease 90 capable normal activity few symptoms/disease 80 normal activity, some difficulty some symptoms/signs 70 caring for self not capable normal activity/work 60 requiring some help can take care of most personal requirements 50 requires help often requires frequent medical care 40 disabled requires special care/help 30 severely disabled hospital admission indicated but no risk of death 20 very ill urgently requiring admission requires supportive measures/treatment 10 moribund rapidly progressive fatal disease processes 0 death
Histology  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 8 participants 40 participants 48 participants
Anaplastic glioma 2 5 7
Gliobastoma 6 35 41
Prior Radiotherapy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 8 participants 40 participants 48 participants
8 40 48
Prior chemotherapy regimens  
Median (Full Range)
Unit of measure:  Number of chemotherapy regimens
Number Analyzed 8 participants 40 participants 48 participants
1
(1 to 2)
1
(1 to 3)
1
(1 to 3)
1.Primary Outcome
Title Number of Participants With Dose-limiting Toxicities Due to Romidepsin Graded According to the NCI Common Toxicity Criteria (CTCAE Version 3.0) (Phase I)
Hide Description

dose limiting toxicity defined as: ANC </=1000 or Platelets <100K; SGOT >/= 3X ULN and T. Bili >/= 1.5 ULN

grade 3 Nausea, vomiting, fatigue and asymptomatic hypocalcemia (treatment may continue after discuss with PI)

Time Frame First 4 weeks of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase 1 Dose Escalation - Romidepsin
Hide Arm/Group Description:

Patients receive FR901228 (romidepsin) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Dose escalation two dose levels:

Romidepsin (depsipeptide): 13.3mg/m2 and 17.7mg/m2

Pharmacokinetics

depsipeptide: Given IV

Overall Number of Participants Analyzed 8
Measure Type: Number
Unit of Measure: participants
0
2.Primary Outcome
Title 6 Months Progression-free Survival (Phase II)
Hide Description evaluated patients with glioblastoma (GBM (35 patients)
Time Frame At 6 months
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Hide Analysis Population Description
evaluation of patients with GBM histology
Arm/Group Title Phase 2 Dose From Phase 1 - Romidepsin
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Patients receive FR901228 (romidepsin) as in phase I at dose level 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity

Romidepsin (depsipeptide): 13.3mg/m2

depsipeptide: Given IV

Overall Number of Participants Analyzed 35
Measure Type: Number
Unit of Measure: percentage of participants
3
3.Secondary Outcome
Title Response Rate Associated With Depsipeptide Therapy (Phase II)
Hide Description

RECIST Complete Response (CR): Complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients must be on no steroids.

Partial Response (PR): Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions.

Stable/No Response: Does not qualify for CR, PR, or progression. The designation of Stable/No Response requires a minimum of 8 weeks duration.

Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR clear clinical worsening or failure to return for evaluation due to death or deteriorating condition

Time Frame Up to 2 years
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Hide Analysis Population Description
GBM patients - no responses
Arm/Group Title Phase 2 Dose From Phase 1 - Romidepsin
Hide Arm/Group Description:

Patients receive FR901228 (romidepsin) as in phase I at dose level 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity

Romidepsin (depsipeptide): 13.3mg/m2

depsipeptide: Given IV

Overall Number of Participants Analyzed 35
Measure Type: Number
Unit of Measure: participants
0
Time Frame 2 years
Adverse Event Reporting Description in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
 
Arm/Group Title Phase 1 Dose Escalation - Romidepsin Phase 2 Dose From Phase 1 - Romidepsin
Hide Arm/Group Description

Patients receive FR901228 (romidepsin) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Dose escalation two dose levels:

Romidepsin (depsipeptide): 13.3mg/m2 and 17.7mg/m2

Pharmacokinetics

depsipeptide: Given IV

Patients receive FR901228 (romidepsin) as in phase I at dose level 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity

Romidepsin (depsipeptide): 13.3mg/m2

depsipeptide: Given IV

All-Cause Mortality
Phase 1 Dose Escalation - Romidepsin Phase 2 Dose From Phase 1 - Romidepsin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Phase 1 Dose Escalation - Romidepsin Phase 2 Dose From Phase 1 - Romidepsin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/8 (0.00%)      0/40 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase 1 Dose Escalation - Romidepsin Phase 2 Dose From Phase 1 - Romidepsin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/8 (100.00%)      40/40 (100.00%)    
Blood and lymphatic system disorders     
anemia * 1  3/8 (37.50%)  3 8/40 (20.00%)  8
Leucopenia * 1  3/8 (37.50%)  3 8/40 (20.00%)  8
neutropenia * 1  3/8 (37.50%)  3 7/40 (17.50%)  7
Thrombocytopenia * 1  6/8 (75.00%)  6 15/40 (37.50%)  15
Gastrointestinal disorders     
nausea * 1  5/8 (62.50%)  5 13/40 (32.50%)  13
vomiting * 1  4/8 (50.00%)  4 3/40 (7.50%)  3
constipation * 1  0/8 (0.00%)  0 7/40 (17.50%)  7
diarrhea * 1  0/8 (0.00%)  0 4/40 (10.00%)  4
heartburn * 1  0/8 (0.00%)  0 2/40 (5.00%)  2
Abdominal pain * 1  0/8 (0.00%)  0 3/40 (7.50%)  3
General disorders     
fatigue * 1  4/8 (50.00%)  4 17/40 (42.50%)  17
gait disturbance * 1 [1]  1/8 (12.50%)  1 0/40 (0.00%)  0
rigors or chills * 1  1/8 (12.50%)  1 0/40 (0.00%)  0
edema-limb * 1  0/8 (0.00%)  0 2/40 (5.00%)  2
Investigations     
lymphopenia * 1  1/8 (12.50%)  1 9/40 (22.50%)  9
Alkaline phosphatase elevation * 1  1/8 (12.50%)  1 1/40 (2.50%)  1
elevated ALT and/or AST * 1  2/8 (25.00%)  2 9/40 (22.50%)  9
Metabolism and nutrition disorders     
anorexia * 1  0/8 (0.00%)  0 4/40 (10.00%)  4
hyperglycemia * 1  1/8 (12.50%)  1 4/40 (10.00%)  4
hypocalcemia * 1  2/8 (25.00%)  2 2/40 (5.00%)  2
hypogycemia * 1  1/8 (12.50%)  1 0/40 (0.00%)  0
hyponatremia * 1  1/8 (12.50%)  1 1/40 (2.50%)  1
hypophosphatemia * 1  3/8 (37.50%)  3 5/40 (12.50%)  5
Hypokalemia * 1  0/8 (0.00%)  0 3/40 (7.50%)  3
Musculoskeletal and connective tissue disorders     
muscle weakness (lower extremity) * 1  0/8 (0.00%)  0 2/40 (5.00%)  2
Joint pain * 1  0/8 (0.00%)  0 3/40 (7.50%)  3
Nervous system disorders     
headache * 1  4/8 (50.00%)  4 1/40 (2.50%)  1
Dizziness * 1  0/8 (0.00%)  0 3/40 (7.50%)  3
Vascular disorders     
hot flashes * 1  1/8 (12.50%)  1 0/40 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[1]
gait or walking difficulties
Dose escalation was terminated after 2 dose levels because PK parameters of romidepsin in pts receiving EIAEDs were similar to those reported in Adults not receiving CYP34A inducing drugs, we wanted to avoid the expected dose limiting toxicity.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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
Name/Title: Howard Fine, MD
Organization: Adult Brain Tumor Consortium (ABTC)
Phone: 410-955-8837
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00085540     History of Changes
Obsolete Identifiers: NCT00103909
Other Study ID Numbers: NCI-2012-02596
NABTC-0303
U01CA062399 ( U.S. NIH Grant/Contract )
CDR0000370817 ( Registry Identifier: PDQ (Physician Data Query) )
First Submitted: June 10, 2004
First Posted: June 11, 2004
Results First Submitted: September 23, 2016
Results First Posted: November 15, 2016
Last Update Posted: January 2, 2017