FR901228 in Treating Patients With Recurrent High-Grade Gliomas

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