Lonafarnib and Temozolomide in Treating Patients With Recurrent Primary Supratentorial Gliomas

February 9, 2015 updated by: European Organisation for Research and Treatment of Cancer - EORTC

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Dijon, France, 21079
        • Centre de Lutte Contre le Cancer Georges-Francois Leclerc
      • Nantes-Saint Herblain, France, 44805
        • Centre Regional Rene Gauducheau
  • Switzerland
      • Lausanne, Switzerland, CH-1011
        • Centre Hospitalier Universitaire Vaudois

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Investigators

  • Study Chair: Mario Campone, MD, Centre Regional Rene Gauducheau

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2004

Primary Completion (Actual)

June 1, 2009

Study Registration Dates

First Submitted

May 14, 2004

First Submitted That Met QC Criteria

May 14, 2004

First Posted (Estimate)

May 17, 2004

Study Record Updates

Last Update Posted (Estimate)

February 10, 2015

Last Update Submitted That Met QC Criteria

February 9, 2015

Last Verified

February 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EORTC-16027-26023
  • EORTC-16027
  • EORTC-26023
  • SPRI-P03174

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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