Lonafarnib and Temozolomide in Treating Patients With Recurrent Primary Supratentorial Gliomas

Brain and Central Nervous System Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00083096
• Other study ID #: EORTC-16027-26023
• Secondary ID: EORTC-16027EORTC
• Status: Active, not recruiting
• Phase: Phase 1
• First received: May 14, 2004
• Last updated: February 9, 2015
• Start date: March 2004

Study information

• Verified date: February 2015
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

Drug:
• lonafarnib

• temozolomide

Locations

Country	Name	City	State
France	Centre de Lutte Contre le Cancer Georges-Francois Leclerc	Dijon
France	Centre Regional Rene Gauducheau	Nantes-Saint Herblain
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

France,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity and maximum tolerated dose of lonafarnib determined by CTCAE v3.0			Yes
Secondary	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			No