FR901228 in Treating Patients With Recurrent High-Grade Gliomas

• Register: ClinicalTrials.gov
• Last refreshed on: 21 January 2013
• Main ID: NCT00085540
• Date of registration: 10/06/2004
• Primary sponsor: National Cancer Institute (NCI)
• Public title: FR901228 in Treating Patients With Recurrent High-Grade Gliomas
• Scientific title: A Phase I-II Trial of Depsipeptide in Patients With Recurrent High-Grade Gliomas
• Date of first enrolment: January 2005
• Target sample size: 80
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00085540
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Howard Fine
• Affiliation: North American Brain Tumor Consortium

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Adult Anaplastic Astrocytoma

Adult Anaplastic Oligodendroglioma

Adult Giant Cell Glioblastoma

Adult Gliosarcoma

Adult Mixed Glioma

Recurrent Adult Brain Tumor

Intervention(s)

Drug: romidepsin

Primary Outcome(s)

Maximum tolerated dose of depsipeptide determined by dose-limiting toxicities graded according to the NCI Common Toxicity Criteria (CTCAE Version 3.0) (Phase I) [Time Frame: First 4 weeks of treatment]

Progression-free survival (Phase II) [Time Frame: At 6 months]

Secondary Outcome(s)

Response rate associated with depsipeptide therapy (Phase II) [Time Frame: Up to]

Secondary ID(s)

CDR0000370817

NABTC-0303

NCI-2012-02596

U01CA062399

Source(s) of Monetary Support

Please refer to primary and secondary sponsors