FR901228 in Treating Patients With Recurrent High-Grade Gliomas

• Status: Completed
• Trial end date: 2009-03-01
• Target enrollment: 0
• Participant gender: All

Summary

This phase I/II trial is studying the side effects and best dose of FR901228 and to see how well it works in treating patients with recurrent high-grade gliomas. FR901228 may stop the growth of tumor cells by blocking the enzymes necessary for their growth

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Romidepsin

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