Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Lonafarnib and Temozolomide in Treating Patients With Recurrent Primary Supratentorial Gliomas

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Active Over 18 Other, Pharmaceutical / Industry EORTC-16027 EORTC-26023, SPRI-P03174, NCT00083096

Objectives

Primary

1. Determine the maximum tolerated dose and dose-limiting toxicity of lonafarnib when administered with temozolomide in patients with recurrent primary supratentorial gliomas.
2. Determine the safety and tolerability of this regimen in these patients.

Secondary

1. Determine the mechanism of action of lonafarnib in these patients.
2. Determine the pharmacodynamics and pharmacokinetics of this regimen in these patients.
3. Determine the activity of this regimen in these patients.
4. Determine the response to this regimen in patients who have measurable disease.

Entry 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

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

Patient Characteristics:

Age

• Over 18

Performance status

• ECOG 0-2

  OR

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• Neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• 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

Expected Enrollment

A total of 3-30 patients will be accrued for this study.

Outcomes

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

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

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.

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Mario Campone, MD, Protocol chair		Ph: 33-02-4067-9977 Email: m-campone@nantes-fnclcc.fr
Roger Stupp, MD, Protocol chair		Ph: 41-21-314-0156 Email: roger.stupp@chuv.ch

France
	Dijon
	Centre de Lutte Contre le Cancer Georges-Francois Leclerc
		Contact Person	Ph:  33-3-8075-7301
	Nantes-Saint Herblain
	Centre Regional Rene Gauducheau
		Contact Person	Ph:  33-02-4067-9977
Switzerland
	Lausanne
	Centre Hospitalier Universitaire Vaudois
		Contact Person	Ph:  41-21-314-0156

Registry Information
Official Title		Phase I Study Of SCH66336 (lonafarnib), A Farnesyl Protein Transferase Inhibitor In Combination With Temozolomide In Gliomas
Trial Start Date		2004-03-10
Trial Completion Date		2008-01-31 (estimated)
Registered in ClinicalTrials.gov		NCT00083096
Date Submitted to PDQ		2004-03-17
Information Last Verified		2008-04-13

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