Lonafarnib and Temozolomide in Treating Patients With Recurrent Primary Supratentorial Gliomas

European Organisation for Research and Treatment of Cancer (EORTC)

Status and phase

Unknown

Phase 1

Conditions

Brain and Central Nervous System Tumors

Treatments

Drug: lonafarnib

Drug: temozolomide

Study type

Interventional

Funder types

NETWORK

Identifiers

NCT00083096

EORTC-26023

EORTC-16027

SPRI-P03174

EORTC-16027-26023

Details and patient eligibility

About

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.

Full 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.

Enrollment

30 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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