Phase I Study Of SCH66336 (Lonafarnib), A Farnesyl Protein Transferase Inhibitor In Combination With Temozolomide In Gliomas
18 Years
N/A
Both
Brain and Central Nervous System Tumors
Trial Information
Phase I Study Of SCH66336 (Lonafarnib), A Farnesyl Protein Transferase Inhibitor In Combination With Temozolomide In Gliomas
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.
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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Dose-limiting toxicity and maximum tolerated dose of lonafarnib determined by CTCAE v3.0
Safety Issue:
Yes
Principal Investigator
Mario Campone, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Centre Regional Rene Gauducheau
Authority:
United States: Federal Government
Study ID:
CDR0000362066
NCT ID:
NCT00083096
Start Date:
March 2004
Completion Date:
Related Keywords:
- Brain and Central Nervous System Tumors
- 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
- Glioma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
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