Tipifarnib and Radiation Therapy in Treating Young Patients With Brainstem Glioma

NCT00079339 | Completed Phase 1 Results

• 3 other identifiers: NCI-2012-03021PBTC-014U01CA081457
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Tipifarnib may make tumor cells more sensitive to radiation therapy. Combining tipifarnib with radiation therapy may kill more tumor cells. This phase I/II trial is studying the side effects and best dose of tipifarnib to see how well it works when given together with radiation therapy in treating young patients with newly diagnosed brain stem glioma. (Phase I closed to accrual as of 1/19/06)

Conditions

Untreated Childhood Brain Stem Glioma

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  Day 1 of tipifarnib therapy to week 8

• Progression-free Survival (PFS)

  PFS was defined as the interval from initiation of treatment to the earliest of disease progression (tumor increase of 25% over baseline tumor measurement; appearance of new lesion(s); or progressive/worsening neurological status) or death for patients who failed, or to the last date of follow up for patients without failure.

  Assessed before the first dose of tipifarnib, every 8 weeks for the first 48 weeks, and then every 12 weeks.

Secondary Outcomes (5)

• Change From Baseline in Perfusion Ratio at Two Weeks After Completion of Radiation

  Baseline and two weeks post completion of radiation

• Change From Baseline in Diffusion Ratio at Two Weeks After Completion of Radiation.

  Baseline and two weeks post completion of radiation

• Change From Baseline in Volume FLAIR at Two Weeks After Completion of Radiation

  Baseline and two weeks post completion of radiation

• Mean Tumor to Gray Matter Ratio Measured at Baseline

  Baseline

• Mean Tumor to White Matter Ratio Measured at Baseline

  Baseline

Study Arms (1)

Treatment (radiation therapy and tipifarnib)

EXPERIMENTAL

PHASE I: 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. 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.

Radiation: radiation therapy; Drug: tipifarnib

Interventions

radiation therapy RADIATION

Undergo radiotherapy

Also known as: irradiation, radiotherapy, therapy, radiation

Treatment (radiation therapy and tipifarnib)

tipifarnib DRUG

Given orally

Also known as: R115777, Zarnestra

Treatment (radiation therapy and tipifarnib)

Eligibility Criteria

• Age: 3 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Newly diagnosed non-disseminated intrinsic diffuse brainstem glioma
• Karnofsky performance scale (KPS) (for \> 16 yrs of age) or Lansky performance score (LPS) (for =\< 16 years of age) =\> 50 assessed within two weeks prior to registration
• Prior/concurrent therapy:
• Chemo: No prior therapy allowed
• Radiation therapy (XRT): No prior therapy allowed
• Bone Marrow Transplant: None prior
• Anti-convulsants: Patients receiving EIACDs will not be eligible; however, patients may switch from EIACDs to non-EIACDs and must then be on non-EIACDs for a minimum of 7 days prior to registration
• Growth factors: Off all colony forming growth factor(s) \> 2 weeks prior to registration (G-CSF, GM-CSF, erythropoietin)
• Absolute neutrophil count \>= 1,000/mm\^3
• Platelets \>= 100,000/mm\^3 (transfusion independent)
• Hemoglobin \>= 8 gm/dL (transfusion independent)
• Serum creatinine that is less than the upper limit of institutional normal for age or GFR \> 70 ml/min/1.73m2
• Bilirubin =\< 1.5 time upper limit of normal for age
• SGPT (ALT) and SGOT (AST) \< 2.5 times institutional upper limit of normal
• Female patients of childbearing potential must have negative serum or urine pregnancy test; patient must not be pregnant or breast-feeding

You may not qualify if:

• Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy; patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism
• Patients with disseminated intrinsic diffuse brainstem glioma
• Patients taking enzyme-inducing anticonvulsant drugs
• Patients with known allergy to topical or systemic imidazoles (e.g., clotrimazole, ketoconazole, miconazole, econazole)
• Patients receiving any other anticancer or experimental drug therapy
• Patients with uncontrolled infection

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Pediatric Brain Tumor Consortium

Memphis, Tennessee, 38105, United States

Location

MeSH Terms

Interventions

Radiotherapy; Radiation; tipifarnib

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Pediatric Brain Tumor Consortium (James M. Boyett, Ph.D)
• Organization: Pediatric Brain Tumor Consortium

james.boyett@stjude.org

901-595-4986

Study Officials

• Daphne Haas-Kogan

  Pediatric Brain Tumor Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2004
• First Posted: March 10, 2004
• Study Start: January 1, 2004
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: May 15, 2014
• Results First Posted: September 24, 2010

Record last verified: 2012-12

Locations

US (1)