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Lonafarnib and Temozolomide in Treating Patients With Recurrent Primary Supratentorial Gliomas

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00083096
Recruitment Status : Unknown
Verified February 2015 by European Organisation for Research and Treatment of Cancer - EORTC.
Recruitment status was:  Active, not recruiting
First Posted : May 17, 2004
Last Update Posted : February 10, 2015
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

Tracking Information
First Submitted Date  ICMJE May 14, 2004
First Posted Date  ICMJE May 17, 2004
Last Update Posted Date February 10, 2015
Study Start Date  ICMJE March 2004
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 8, 2006)
Dose-limiting toxicity and maximum tolerated dose of lonafarnib determined by CTCAE v3.0
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 28, 2007)
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
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Lonafarnib and Temozolomide in Treating Patients With Recurrent Primary Supratentorial Gliomas
Official Title  ICMJE Phase I Study Of SCH66336 (Lonafarnib), A Farnesyl Protein Transferase Inhibitor In Combination With Temozolomide In Gliomas
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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Brain and Central Nervous System Tumors
Intervention  ICMJE
  • Drug: lonafarnib
  • Drug: temozolomide
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: November 8, 2006)
30
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00083096
Other Study ID Numbers  ICMJE EORTC-16027-26023
EORTC-16027
EORTC-26023
SPRI-P03174
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party European Organisation for Research and Treatment of Cancer - EORTC
Study Sponsor  ICMJE European Organisation for Research and Treatment of Cancer - EORTC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Mario Campone, MD Centre Regional Rene Gauducheau
PRS Account European Organisation for Research and Treatment of Cancer - EORTC
Verification Date February 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP