Brain and Central Nervous System Tumors
Conditions
Keywords
recurrent adult brain tumor, adult mixed glioma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult glioblastoma, adult pilocytic astrocytoma, adult anaplastic ependymoma, adult subependymoma, adult myxopapillary ependymoma, adult oligodendroglioma, adult giant cell glioblastoma, adult gliosarcoma, adult diffuse astrocytoma, adult subependymal giant cell astrocytoma, adult pineal gland astrocytoma
Brief summary
RATIONALE: Lonafarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving lonafarnib together with temozolomide may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of lonafarnib when given together with temozolomide in treating patients with recurrent primary supratentorial glioma.
Detailed description
OBJECTIVES: Primary * Determine the maximum tolerated dose and dose-limiting toxicity of lonafarnib when administered with temozolomide in patients with recurrent primary supratentorial gliomas. * Determine the safety and tolerability of this regimen in these patients. Secondary * Determine the mechanism of action of lonafarnib in these patients. * Determine the pharmacodynamics and pharmacokinetics of this regimen in these patients. * Determine the activity of this regimen in these patients. * Determine the response to this regimen in patients who have measurable disease. OUTLINE: This is a nonrandomized, multicenter, open-label, dose-escalation study of lonafarnib. Patients receive oral temozolomide once daily on days 2-6 of course 1 and on days 1-5 of all subsequent courses. Patients also receive oral lonafarnib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of lonafarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 1 of 6 patients experience dose-limiting toxicity. An additional 3 patients may be treated at the highest dose level achieved. Patients are followed every 8 weeks for 6 months and then every 3 months thereafter. PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study.
Interventions
DRUGlonafarnib
DRUGtemozolomide
Sponsors
European Organisation for Research and Treatment of Cancer - EORTC
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed primary supratentorial glioma * Multifocal disease allowed * Recurrent disease after prior surgery and/or radiotherapy * Radiological evidence of increased and/or enhanced target lesion * Amenable to temozolomide therapy PATIENT CHARACTERISTICS: Age * Over 18 Performance status * ECOG 0-2 OR * WHO 0-2 Life expectancy * Not specified Hematopoietic * Neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 10.0 g/dL Hepatic * Alkaline phosphatase \< 2.5 times upper limit of normal (ULN) * Transaminases \< 2.5 times ULN * Bilirubin \< 1.5 times ULN Renal * Creatinine \< 1.7 mg/dL Cardiovascular * Cardiac function clinically normal * Normal 12-lead ECG * QTc ≤ 440 msec on ECG * No ischemic heart disease within the past 6 months Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after study participation * No unstable systemic disease * No active uncontrolled infection * No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up * No other active or recurrent malignancy within the past 5 years except cone biopsied carcinoma of the cervix or adequately treated basal cell or squamous cell skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy * No concurrent anticancer biologic agents Chemotherapy * At least 4 weeks since prior chemotherapy (6 weeks for temozolomide) * Prior adjuvant chemotherapy allowed * No more than 1 prior chemotherapy regimen for recurrent disease * No other concurrent chemotherapy Endocrine therapy * Concurrent corticosteroids allowed provided treatment remains at a stable or decreasing dose for at least 2 weeks Radiotherapy * See Disease Characteristics * No concurrent radiotherapy Surgery * See Disease Characteristics * At least 3 months since prior surgery for primary brain tumor Other * Concurrent anticonvulsants allowed * No other concurrent anticancer agents * No other concurrent investigational therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicity and maximum tolerated dose of lonafarnib determined by CTCAE v3.0 | — |
Secondary
| Measure | Time frame |
|---|---|
| Response (complete [CR] or partial response [PR]) measured by McDonald's criteria at least 4 weeks after first documented response and every 8 weeks until disease progression or until start of another treatment | — |
Countries
France, Switzerland
Outcome results
None listed