Know Cancer

forgot password

Phase I/II Trial Of R115777 And XRT In Pediatric Patients With Newly Diagnosed Non-Disseminated Intrinsic Diffuse Brainstem Gliomas

Phase 1/Phase 2
3 Years
21 Years
Not Enrolling
Brain and Central Nervous System Tumors

Thank you

Trial Information

Phase I/II Trial Of R115777 And XRT In Pediatric Patients With Newly Diagnosed Non-Disseminated Intrinsic Diffuse Brainstem Gliomas



- Determine the maximum tolerated dose (MTD) of tipifarnib when administered with
radiotherapy in patients with non-disseminated, diffuse, intrinsic brainstem gliomas.

- Determine the efficacy of this regimen in these patients.


- Determine the toxic effects of this regimen in these patients.

- Determine the radiographic changes of brainstem gliomas using magnetic resonance
imaging (MRI), perfusion and diffusion imaging, and positron-emission tomography scans
in patients treated with this regimen.

OUTLINE: This is a phase I (closed to accrual as of 1/19/06), multicenter, dose-escalation
study of tipifarnib followed by a phase II safety and efficacy study.

- Phase I (closed to accrual as of 1/19/06): 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 (total of 26 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 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 1/19/06) . Treatment continues for up to 24 months (26
courses) in the absence of disease progression or unacceptable toxicity.


Phase I: Participants contributing only to the phase I part are followed for 90 days after
completion of therapy. Adverse events that have not resolved within 90 days after stopping
treatment will be followed until resolution.

Phase II: Participants in the phase I part treated at the MTD or participants in the phase
II part are followed until the earliest of death or three years after starting treatment.

PROJECTED ACCRUAL: A total of 3-55 patients (3-18 patients for phase I [closed to accrual as
of 1/19/06] 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 1/19/06)]) will be accrued for this
study within 2.3 years.

Inclusion Criteria

- Histologically confirmed non-disseminated, intrinsic diffuse brainstem glioma

- Newly diagnosed disease

- Must be over 3 years of age

- Must be under 21 years of age

- Karnofsky 50-100% (patients 17 and older) or Lansky 50-100% (patients under 17)

- Absolute neutrophil count ≥1,000/mm3

- Platelet count ≥ 100,000/mm3

- Hemoglobin ≥ 8 g/dL (Transfusion independent)

- ALT and AST < 2.5 time upper limit of normal (ULN)

- Bilirubin ≤ 1.5 ULN

- Creatinine < ULN or Glomerular filtration rate > 70 mL/min

- 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

- More than 2 weeks since prior filgrastim (G-CSF), sargramostim (GM-CSF) or epoetin

- No prior bone marrow transplantation

- No prior chemotherapy

- No prior radiotherapy

- 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

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants in the Phase I Component With Dose-limiting Toxicities (DLTs) Observed During the First 8 Weeks (Courses 1 and 2) of Tipifarnib Therapy

Outcome Description:

The dose limiting toxicity (DLT) analysis population consists of phase I participants who developed DLT during the maximum tolerated dose (MTD) estimation period (courses 1 and 2) or who completed the MTD estimation period (courses 1 and 2) without DLTs. DLTs observed during courses 1 and 2 were used to estimate the MTD.

Outcome Time Frame:

Day 1 of tipifarnib therapy to week 8

Safety Issue:


Principal Investigator

Daphne A. Haas-Kogan, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, San Francisco


United States: Food and Drug Administration

Study ID:




Start Date:

March 2004

Completion Date:

November 2010

Related Keywords:

  • Brain and Central Nervous System Tumors
  • untreated childhood brain stem glioma
  • Glioma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms



Children's Hospital of Philadelphia Philadelphia, Pennsylvania  19104
Duke Comprehensive Cancer Center Durham, North Carolina  27710
Children's National Medical Center Washington, District of Columbia  20010-2970
Children's Hospital of Pittsburgh Pittsburgh, Pennsylvania  15213
Children's Hospital and Regional Medical Center - Seattle Seattle, Washington  98105
Children's Memorial Hospital - Chicago Chicago, Illinois  60614
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Boston, Massachusetts  02115
St. Jude Children's Research Hospital Memphis, Tennessee  38105-2794
UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, California  94115
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Bethesda, Maryland  20892-1182
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital Houston, Texas  77030-2399