FR901228 in Treating Patients With Recurrent High-Grade Gliomas
|Adult Anaplastic Astrocytoma Adult Anaplastic Oligodendroglioma Adult Giant Cell Glioblastoma Adult Gliosarcoma Recurrent Adult Brain Tumor||Drug: depsipeptide||Phase 1 Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I-II Trial of Depsipeptide in Patients With Recurrent High-Grade Gliomas|
- Number of Participants With Dose-limiting Toxicities Due to Romidepsin Graded According to the NCI Common Toxicity Criteria (CTCAE Version 3.0) (Phase I) [ Time Frame: First 4 weeks of treatment ]
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)
- 6 Months Progression-free Survival (Phase II) [ Time Frame: At 6 months ]evaluated patients with glioblastoma (GBM (35 patients)
- Response Rate Associated With Depsipeptide Therapy (Phase II) [ Time Frame: Up to 2 years ]
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
|Study Start Date:||January 2005|
|Study Completion Date:||March 2009|
|Primary Completion Date:||December 2008 (Final data collection date for primary outcome measure)|
Experimental: Phase 1 Dose Escalation - Romidepsin
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
Experimental: Phase 2 Dose from Phase 1 - Romidepsin
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
I. Determine the maximum tolerated dose (MTD) of FR901228 (depsipeptide) in patients with recurrent malignant gliomas who are taking enzyme-inducing antiepileptic drugs (EIAEDs). (Phase I) II. Determine the safety profile of this drug in these patients. (Phase I) III. Determine the pharmacokinetics and pharmacodynamics of this drug in these patients. (Phase I) IV. Determine the clinical efficacy of this drug, as measured by 6-month progression-free survival and objective tumor response, in these patients. (Phase II) V. Determine the safety profile of this drug when administered at the phase I MTD concurrently with or without EIAEDs in these patients. (Phase II)
OUTLINE: This is a multicenter, phase I, dose-escalation study followed by a phase II study. Patients are stratified according to study phase (I vs II), concurrent use of enzyme-inducing anti-epileptic drugs (EIAEDs) (yes vs no), histology (recurrent glioblastoma multiforme/gliosarcoma vs recurrent anaplastic glioma), pre-operative candidacy (yes vs no), and measurable/evaluable disease (yes vs no). Patients are assigned to 1 of 2 treatment groups (group A: no EIAEDs or group B: concurrent use of EIAEDs).
Phase I (group B only): Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of FR901228 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of up to 6 patients experience dose-limiting toxicity.
Phase II (groups A and B):
Group A (phase II): Patients receive FR901228 as in phase I at dose level 1. Group B (phase II): Patients receive FR901228 as in phase I at the MTD.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00085540
|United States, California|
|University of California Los Angeles|
|Los Angeles, California, United States, 90095|
|University of California San Francisco|
|San Francisco, California, United States, 94143|
|United States, Maryland|
|National Cancer Institute Neuro-Oncology Branch|
|Bethesda, Maryland, United States, 20814|
|United States, Massachusetts|
|Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10021|
|United States, Pennsylvania|
|University of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15232|
|United States, Texas|
|MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|United States, Wisconsin|
|University of Wisconsin|
|Madison, Wisconsin, United States, 53792|
|Principal Investigator:||Howard Fine, MD||North American Brain Tumor Consortium|