Oral ST1481 in Adults With Malignant Glioma: A Phase I-II Clinical Trial
Data Collection
Astrocytoma+16
+ Brain Diseases
+ Brain Neoplasms
Treatment Study
Summary
Study start date: May 1, 2004
Actual date on which the first participant was enrolled.OBJECTIVES: Primary * Determine the maximum tolerated dose (MTD) of gimatecan in patients with recurrent or progressive primary malignant glioma treated with or without concurrent enzyme-inducing anticonvulsant drugs. * Determine whether this drug has sufficient activity to warrant further development in these patients. (phase II) Secondary * Determine the qualitative and quantitative toxic effects of this drug in these patients. * Determine the pharmacokinetic behaviors of this drug in these patients. * Correlate the principal toxic effects with the pertinent pharmacokinetic parameters of this drug in these patients. * Determine the antitumor activity of this drug in these patients. OUTLINE: This is an open-label, dose-escalation, multicenter study. Patients are stratified according to the concurrent use of enzyme-inducing anticonvulsant drugs (yes vs no). * Phase I: Patients receive oral gimatecan once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gimatecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. * Phase II: Patients receive gimatecan as in phase I at the MTD. Patients are followed for at least 1 month and then every 2 months thereafter. PROJECTED ACCRUAL: Approximately 30-83 patients (30-42 for phase I \[15-21 per stratum\] and 21-41 for phase II) will be accrued for this study within 24 months.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
DISEASE CHARACTERISTICS: * Histologically confirmed malignant glioma (glioblastoma multiforme, anaplastic astrocytoma, or anaplastic oligodendroglioma) * Recurrent or progressive primary CNS neoplasm by contrast-enhanced MRI * Tumor progression after prior surgery, radiotherapy, or chemotherapy * Measurable or evaluable disease * Failed prior standard curative or palliative therapy (phase I only) PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Karnofsky 60-100% Life expectancy * At least 3 months Hematopoietic * Absolute neutrophil count ≥ 2,000/mm\^3 * Platelet count ≥ 100,000/mm\^3 Hepatic * SGPT and SGOT ≤ 1.5 times upper limit of normal (ULN) (3 times ULN if liver metastases are present) * Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN if liver metastases are present) * Bilirubin normal Renal * Creatinine ≤ 1.5 times ULN Cardiovascular * No myocardial infarction with the past year * No heart failure (including cardiac insufficiency controlled by digitalis and diuretics) * No irreversible arrhythmias requiring permanent medication * No uncontrolled hypertension Gastrointestinal * No gastrointestinal dysfunction that would alter absorption or motility, such as any of the following: * Active peptic ulcer * Inflammatory bowel disease * Known intolerance to lactose * Malabsorption syndromes * Intestinal sub-occlusion Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception * No active infection * No mentally incapacitated patients * No other concurrent severe disease that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy * No concurrent immunotherapy Chemotherapy * See Disease Characteristics * At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) * No more than 1 prior chemotherapy regimen * No other concurrent chemotherapy Endocrine therapy * Concurrent corticosteroids allowed if dose stable for the past 2 weeks * No concurrent hormonal therapy Radiotherapy * See Disease Characteristics * At least 4 weeks since prior radiotherapy * No concurrent radiotherapy Surgery * See Disease Characteristics * At least 3 weeks since prior surgical resection * No prior gastrointestinal surgery that would affect drug absorption Other * More than 4 weeks since prior participation in any other investigational drug study * More than 72 hours since prior systemic antibiotics * No concurrent H2 antagonists, antacids, or proton pump inhibitors * If any of these therapies are necessary, ≥ 3 hours must elapse after gimatecan administration * No other concurrent anticancer therapy * No other concurrent investigational drugs * No other concurrent immunosuppressive agents
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 1 location
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, United StatesOpen Jonsson Comprehensive Cancer Center at UCLA in Google Maps