Lonafarnib and Temozolomide in Treating Patients With Recurrent Primary Supratentorial Gliomas
Recruitment status was Active, not recruiting
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Brain and Central Nervous System Tumors |
Drug: lonafarnib Drug: temozolomide |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase I Study Of SCH66336 (Lonafarnib), A Farnesyl Protein Transferase Inhibitor In Combination With Temozolomide In Gliomas |
- Dose-limiting toxicity and maximum tolerated dose of lonafarnib determined by CTCAE v3.0 [ Designated as safety issue: Yes ]
- 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 [ Designated as safety issue: No ]
| Estimated Enrollment: | 30 |
| Study Start Date: | March 2004 |
| Estimated Primary Completion Date: | January 2008 (Final data collection date for primary outcome measure) |
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| France | |
| Centre de Lutte Contre le Cancer Georges-Francois Leclerc | |
| Dijon, France, 21079 | |
| Centre Regional Rene Gauducheau | |
| Nantes-Saint Herblain, France, 44805 | |
| Switzerland | |
| Centre Hospitalier Universitaire Vaudois | |
| Lausanne, Switzerland, CH-1011 | |
| Study Chair: | Mario Campone, MD | Centre Regional Rene Gauducheau |
| Study Chair: | Roger Stupp, MD | Centre Hospitalier Universitaire Vaudois |
More Information
Additional Information:
No publications provided
| ClinicalTrials.gov Identifier: | NCT00083096 History of Changes |
| Other Study ID Numbers: | CDR0000362066, EORTC-16027, EORTC-26023, SPRI-P03174 |
| Study First Received: | May 14, 2004 |
| Last Updated: | July 9, 2009 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Cancer Institute (NCI):
|
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 |
Additional relevant MeSH terms:
|
Glioma Nervous System Neoplasms Central Nervous System Neoplasms Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue |
Neoplasms by Site Nervous System Diseases Temozolomide Dacarbazine Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on June 18, 2013