Completed

A Phase I-II Trial of Depsipeptide in Patients With Recurrent High-Grade Gliomas

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What is being tested

depsipeptide

Drug
Who is being recruted

Astrocytoma
+12

+ Glioblastoma
+ Glioma
Over 18 Years
See all eligibility criteria
How is the trial designed

Treatment Study

Phase 1 & 2
Interventional
Study Start: January 2005
See protocol details

Summary

Principal SponsorNational Cancer Institute (NCI)
Last updated: January 14, 2026
Sourced from a government-validated database.Claim as a partner
Study start date: January 1, 2005Actual date on which the first participant was enrolled.

PRIMARY OBJECTIVES: 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.

Official TitleA Phase I-II Trial of Depsipeptide in Patients With Recurrent High-Grade Gliomas 
NCT00103909NCT00085540
Principal SponsorNational Cancer Institute (NCI)
Last updated: January 14, 2026
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
50 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, participants are assigned to groups based on specific criteria, such as their medical history or a doctor's recommendation. This approach ensures that treatments are given to those who may benefit the most, based on known factors.

Other Ways to Assign Participants
Randomized allocation
: Participants are assigned randomly, like flipping a coin, to ensure fairness and reduce bias.

None (Single-arm trial)
: If the study has only one group, all participants receive the same treatment, and no allocation is needed.

How treatments are given to participants
In this study, all participants receive the same treatment. This approach is often used to evaluate the effects of a single intervention without comparing it to another.

Other Ways to Assign Treatments
Parallel assignment
: Participants are split into separate groups, each receiving a different treatment.

Cross-over assignment
: Participants switch between treatments during the study.

Factorial assignment
: Participants receive different combinations of treatments.

Sequential assignment
: Participants receive treatments one after another in a specific order, possibly based on individual responses.

Other assignment
: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled
: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind
: Participants do not know which treatment they are receiving, but researchers do.

Double-blind
: Neither participants nor researchers know which treatment is given.

Triple-blind
: Participants, researchers, and outcome assessors do not know which treatment is given.

Quadruple-blind
: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Over 18 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Astrocytoma
Glioblastoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Oligodendroglioma
Pathologic Processes
Recurrence
Neuroectodermal Tumors
Neoplasms, Neuroepithelial
Gliosarcoma
Disease Attributes
Criteria

Inclusion Criteria: * Phase I and phase II: * Histologically confirmed recurrent intracranial malignant glioma, including any of the following: * Glioblastoma multiforme * Gliosarcoma * Anaplastic astrocytoma * Anaplastic oligodendroglioma * Anaplastic mixed oligoastrocytoma * Malignant astrocytoma not otherwise specified * Unequivocal evidence of tumor progression by MRI or CT scan while on a steroid dosage that has been stable for at least 5 days * Patients previously treated with interstitial brachytherapy or stereotactic radiosurgerymust have confirmation of true progressive disease (rather than radiation necrosis) by positron-emission tomography, thallium scan, magnetic resonance spectroscopy, or surgical documentation * Must have failed prior radiotherapy that was completed at least 6 weeks ago * No more than 2 prior therapies (initial treatment and treatment for 1 relapse)\* * Surgical resection for relapsed disease with no anticancer therapy for up to 12 weeks, followed by a second surgical resection, is considered treatment for 1 relapse * Patients in group B must have been receiving enzyme-inducing antiepileptic drugs (EIAEDs) for at least the past 2 weeks * Performance status - Karnofsky 60-100% * More than 8 weeks * WBC ≥ 3,000/mm\^3 * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 10 g/dL (transfusions allowed) * SGOT \< 2 times upper limit of normal (ULN) * Bilirubin \< 2 times ULN * Creatinine \< 1.5 mg/dL * No congestive heart failure (i.e., New York Heart Association class II-IV, ejection fraction \< 40% by MUGA scan or \< 50% by echocardiogram and/or MRI) * No myocardial infarction within the past year * No uncontrolled dysrhythmias * No poorly controlled angina * No significant left ventricular hypertrophy by EKG * No cardiac ischemia (ST depression of 2 mm) by EKG * No hypertrophic or restrictive cardiomyopathy from prior treatment or other causes * No uncontrolled hypertension (i.e., blood pressure ≥ 160/95 mm Hg) * No cardiac arrhythmia requiring antiarrhythmic medication * No known cardiac abnormalities (e.g., congenital long QT syndrome and QTc interval \> 480 milliseconds) * No history of sustained ventricular tachycardia, ventricular fibrillation, Torsade de Pointes, or cardiac arrest unless controlled with concurrent automatic implantable cardioverter defibrillator * No known history of coronary artery disease (e.g., Canadian class II-IV angina) * No other significant cardiac disease * No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix * No active infection * No significant uncontrolled medical illness that would preclude study participation * No disease that would obscure toxicity or dangerously alter drug metabolism * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception during and for at least 2 weeks after study participation * Fertile male patients must continue barrier contraception for 3 months after study participation * At least 1 week since prior interferon or thalidomide * No concurrent prophylactic filgrastim (G-CSF) * No concurrent anticancer immunotherapy * At least 2 weeks since prior vincristine * At least 6 weeks since prior nitrosoureas * At least 3 weeks since prior procarbazine * No prior FR901228 (depsipeptide) * No other concurrent anticancer chemotherapy * See Disease Characteristics * At least 1 week since prior tamoxifen * No concurrent anticancer hormonal therapy * See Disease Characteristics * No concurrent anticancer radiotherapy * See Disease Characteristics * Prior recent resection of recurrent or progressive tumor allowed if patient has recovered * Recovered from all prior therapy * At least 2 weeks since prior EIAEDs (patients in Group A only) * At least 4 weeks since prior cytotoxic therapy * At least 4 weeks since prior investigational agents * At least 1 week since prior isotretinoin * At least 1 week since other prior non-cytotoxic therapy (except radiosensitizers) * No concurrent valproic acid * No concurrent hydrochlorothiazide * No concurrent medication that causes QTc prolongation * No other concurrent anticancer therapy * No other concurrent investigational drugs

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
2 intervention groups 

are designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
Experimental
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

Given IV
Group II
Experimental
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

Given IV
Study Objectives
Primary Objectives

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)

evaluated patients with glioblastoma (GBM (35 patients)
Secondary Objectives

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 Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 8 locations
Suspended
University of California Los AngelesLos Angeles, United StatesSee the location
Suspended
University of California San FranciscoSan Francisco, United States
Suspended
National Cancer Institute Neuro-Oncology BranchBethesda, United States
Suspended
Dana Farber Cancer InstituteBoston, United States
Completed8 Study Centers