Overview

This trial is active, not recruiting.

Condition brain and central nervous system tumors
Treatments lonafarnib, temozolomide
Phase phase 1
Sponsor European Organisation for Research and Treatment of Cancer - EORTC
Start date March 2004
End date June 2009
Trial size 30 participants
Trial identifier NCT00083096, EORTC-16027, EORTC-16027-26023, EORTC-26023, SPRI-P03174

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Masking open label
Primary purpose treatment

Primary Outcomes

Measure
Dose-limiting toxicity and maximum tolerated dose of lonafarnib determined by CTCAE v3.0
time frame:

Secondary Outcomes

Measure
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
time frame:

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title Phase I Study Of SCH66336 (Lonafarnib), A Farnesyl Protein Transferase Inhibitor In Combination With Temozolomide In Gliomas
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.
Trial information was received from ClinicalTrials.gov and was last updated in February 2015.
Information provided to ClinicalTrials.gov by European Organisation for Research and Treatment of Cancer - EORTC.