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

Alternate Title

Tipifarnib and Radiation Therapy in Treating Young Patients With Brainstem Glioma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Closed	3 to 21	NCI	PBTC-014 NCT00079339

Objectives

Primary

1. Determine the maximum tolerated dose of tipifarnib when administered with radiotherapy in patients with non-disseminated, diffuse, intrinsic brainstem gliomas.
2. Determine the efficacy of this regimen in these patients.

Secondary

1. Determine the toxic effects of this regimen in these patients.
2. Determine the radiographic changes of brainstem gliomas using MRI, perfusion and diffusion imaging, and positron-emission tomography scans in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed non-disseminated, intrinsic diffuse brainstem glioma
  • Newly diagnosed disease
  • No disseminated disease

Prior/Concurrent Therapy:

Biologic therapy

• More than 2 weeks since prior filgrastim (G-CSF), sargramostim (GM-CSF), or epoetin alfa
• No prior bone marrow transplantation

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy

Surgery

• Not specified

Other

• No concurrent enzyme-inducing anticonvulsant drugs (EIACD)
  • Patients switched from EIACD to non-EIACD for at least 7 days before study participation allowed
• No other concurrent anticancer therapy
• No other concurrent experimental drugs

Patient Characteristics:

Age

• 3 to 21

Performance status

• Karnofsky 50-100% (patients 17 to 21 years of age)

  OR

• Lansky 50-100% (patients 3 to 16 years of age)

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm³
• Platelet count ≥ 100,000/mm³*
• Hemoglobin ≥ 8 g/dL*

 [Note: *Transfusion independent]

Hepatic

• ALT and AST < 2.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 ULN

Renal

• Creatinine < ULN

  OR

• Glomerular filtration rate > 70 mL/min

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 6 months after study participation
• No other significant medical illness that would preclude study participation
• No uncontrolled infection
• No disease that would obscure toxicity or dangerously alter drug metabolism
• No known allergy to topical or systemic azoles (e.g., fluconazole, ketoconazole, or itraconazole)

Expected Enrollment

A total of 3-46 patients (3-12 patients for phase I [closed to accrual as of 1/3/06] and a total of 40 patients for phase II [including 6 patients treated in the dose-finding portion of phase I (closed to accrual as of 1/3/06)]) will be accrued for this study within 2.3 years.

Outcomes

Progression-free survival at 1 year

Outline

This is a phase I (closed to accrual as of 1/3/06), multicenter, dose-escalation study of tipifarnib followed by a phase II safety and efficacy study.

• Phase I (closed to accrual as of 1/3/06): Patients undergo radiotherapy 5 days a week for 6 weeks. Beginning 0-2 days before radiotherapy, patients receive oral tipifarnib twice daily until the completion of radiotherapy. Beginning 2 weeks after the completion of radiotherapy, patients receive oral tipifarnib twice daily in weeks 1-3. Treatment repeats every 4 weeks for up to 24 additional courses in the absence of disease progression or unacceptable toxicity.

  Cohorts of 3-6 patients receive escalating doses of tipifarnib during radiotherapy until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose level preceding that at which 2 of 6 patients experience dose-limiting toxicity.




• Phase II: Patients undergo radiotherapy and receive tipifarnib at the MTD as in phase I (closed to accrual as of 1/3/06) . Treatment continues for up to 24 months (26 courses) in the absence of disease progression or unacceptable toxicity.

Patients are followed for up to 1 year.

Haas-Kogan DA, Banerjee A, Kocak M, et al.: Phase I trial of tipifarnib in children with newly diagnosed intrinsic diffuse brainstem glioma. Neuro Oncol 10 (3): 341-7, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Pediatric Brain Tumor Consortium

Daphne Haas-Kogan, MD, Protocol chair		Ph: 415-353-7175; 800-888-8664
Anuradha Banerjee, MD, Protocol co-chair		Ph: 415-353-2966; 800-888-8664

Registry Information
Official Title		Phase I/II Trial Of R115777 And XRT In Pediatric Patients With Newly Diagnosed Non-Disseminated Intrinsic Diffuse Brainstem Gliomas
Trial Start Date		2004-03-03
Trial Completion Date		2008-12-26 (estimated)
Registered in ClinicalTrials.gov		NCT00079339
Date Submitted to PDQ		2004-01-30
Information Last Verified		2007-10-11
NCI Grant/Contract Number		CA81457

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