Clinical Trial Finder

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

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.#46;II), concurrent use of enzyme-inducing anti-epileptic drugs (EIAEDs) (yes vs.#46;no), histology (recurrent glioblastoma multiforme/gliosarcoma vs.#46;recurrent anaplastic glioma), pre-operative candidacy (yes vs.#46;no), and measurable/evaluable disease (yes vs.#46;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.

Arms

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 Pharmacokinetics

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

Interventions

Drug: - depsipeptide

Given IV