Lonafarnib and Temozolomide in Treating Patients With Recurrent Primary Supratentorial Gliomas

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Unknown status

CT.gov ID

NCT00083096

Collaborator

(none)

Enrollment

Locations

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Drug: lonafarnib Drug: temozolomide	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I Study Of SCH66336 (Lonafarnib), A Farnesyl Protein Transferase Inhibitor In Combination With Temozolomide In Gliomas

Study Start Date :

Mar 1, 2004

Actual Primary Completion Date :

Jun 1, 2009

Outcome Measures

Primary Outcome Measures

Dose-limiting toxicity and maximum tolerated dose of lonafarnib determined by CTCAE v3.0 []

Secondary Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	Country	Postal Code
1	Centre de Lutte Contre le Cancer Georges-Francois Leclerc	Dijon	France	21079
2	Centre Regional Rene Gauducheau	Nantes-Saint Herblain	France	44805
3	Centre Hospitalier Universitaire Vaudois	Lausanne	Switzerland	CH-1011