Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00070525

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

This phase II trial is studying how well tipifarnib works in treating young patients with recurrent or progressive high-grade glioma, medulloblastoma, primitive neuroectodermal tumor, or brain stem glioma. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

Condition or Disease	Intervention/Treatment	Phase
Childhood High-grade Cerebral Astrocytoma Childhood Oligodendroglioma Recurrent Childhood Brain Stem Glioma Recurrent Childhood Cerebellar Astrocytoma Recurrent Childhood Cerebral Astrocytoma Recurrent Childhood Medulloblastoma Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor Recurrent Childhood Visual Pathway and Hypothalamic Glioma	Drug: tipifarnib	Phase 2

Detailed Description

OBJECTIVES:

Determine the response rate in pediatric patients with recurrent or progressive high-grade glioma, medulloblastoma/primitive neuroectodermal tumor (PNET), or brain stem glioma treated with tipifarnib.
Determine the distribution of time to progression, time to treatment failure, and time to death in patients treated with this drug.

OUTLINE: This is an open-label, multicenter study. Patients are stratified according to disease (high-grade glioma vs recurrent or progressive medulloblastoma/primitive neuroectodermal tumor [PNET] vs progressive diffuse, intrinsic brain stem glioma).

Patients receive oral tipifarnib twice daily on days 1-21. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study of R115777 (Zarnestra) (NSC # 702818, IND# 58,359) in Children With Recurrent or Progressive: High Grade Glioma, Medulloblastoma/PNET or Brainstem Glioma

Study Start Date :

Nov 1, 2003

Actual Primary Completion Date :

Sep 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive oral tipifarnib twice daily on days 1-21. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.	Drug: tipifarnib Given orally

Arm

Intervention/Treatment

Experimental: Arm I

Patients receive oral tipifarnib twice daily on days 1-21. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Drug: tipifarnib

Given orally

Outcome Measures

Primary Outcome Measures

Best objective tumor response rates (complete and partial response), based on MRIs [Up to 2 years]
Estimated ultimately as a simple binomial proportion. Estimated actuarially, using the product-limit (PL) estimate.
Time to tumor progression (TTP) [Time from study enrollment to radiographically determined tumor progression or recurrence, assessed up to 2 years]
The distribution of TTP will be analyzed using PL estimate.
Time to treatment failure (TTF) [Time from study enrollment to tumor progression, tumor recurrence, death from any cause, or occurrence of a second malignant neoplasm, assessed up to 2 years]
The distribution of TTF will be analyzed using PL estimate.
Time to death (TTD) [Time from study enrollment to death from any cause, assessed up to 2 years]
The distribution of TTD will be analyzed using PL estimate.
Incidence of adverse events graded according to NCI CTCAE version 3.0 [Up to 2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed brain tumor, including the following:
Anaplastic astrocytoma
Glioblastoma multiforme
Gliosarcoma
Anaplastic oligodendroglioma
Medulloblastoma/primitive neuroectodermal tumor (PNET)
Diffuse intrinsic brain stem glioma*
Progressive or relapsed disease after prior conventional therapy
Radiographic evidence of measurable disease
Performance status - Karnofsky 60-100% (over 16 years of age)
Performance status - Lansky 60-100% (16 years of age and under)
Performance status - ECOG 0-2
At least 8 weeks
Absolute neutrophil count at least 1,000/mm^3
Platelet count at least 100,000/mm^3 (transfusion independent)
Hemoglobin at least 8.0 g/dL (red blood cell transfusions allowed)
Bilirubin no greater than 1.5 times upper limit of normal (ULN)
SGPT and SGOT less than 2.5 times ULN
Creatinine clearance OR radioisotope glomerular filtration rate at least 70 mL/min
Maximum creatinine based on age as follows:
0.8 mg/dL (5 years and under)
1.0 mg/dL (6 to 10 years)
1.2 mg/dL (11 to 15 years)
1.5 mg/dL (over 15 years)
Shortening fraction at least 27% by echocardiogram
Ejection fraction at least 50% by MUGA
No dyspnea at rest
No exercise intolerance
Pulse oximetry greater than 94%*
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Seizure disorder is allowed provided it is well-controlled on non-enzyme-inducing anticonvulsants
No active graft-versus-host disease
No uncontrolled infection
No allergy to azoles (e.g., ketoconazole, itraconazole, or fluconazole)
Recovered from prior immunotherapy
At least 7 days since prior antineoplastic biologic agents
At least 1 month since prior autologous stem cell transplantation (SCT)
At least 6 months since prior allogeneic SCT
More than 1 week since prior growth factors
No concurrent immunomodulating agents
More than 2 weeks since prior myelosuppressive chemotherapy (4-6 weeks for nitrosoureas or temozolomide) and recovered
No concurrent anticancer chemotherapy
Concurrent dexamethasone allowed provided patient is on a stable or decreasing dose for at least 1 week prior to study entry
Concurrent corticosteroids allowed only for treatment of increased intracranial pressure
Recovered from prior radiotherapy
At least 2 weeks since prior local palliative radiotherapy (small port)
At least 3 months since prior craniospinal radiotherapy
At least 6 weeks since other prior substantial bone marrow radiotherapy
No concurrent palliative radiotherapy
No prior initiation of therapy on another phase II study
No concurrent participation in another therapeutic COG study
No concurrent enzyme-inducing anticonvulsants
No other concurrent anticancer or experimental drugs
No concurrent foods or medications that interfere with CYP3A4, including any of the following:
Carbamazepine
Phenytoin
Phenobarbital
Grapefruit juice
Erythromycin
Azithromycin
Clarithromycin
Rifampin and its analogues
Fluconazole
Ketoconazole
Itraconazole
Cimetidine
Cannabinoids (i.e., marijuana or dronabinol)
Omeprazole
Hypericum perforatum (St. John's wort)
Ethosuximide
Glucocorticoids
Griseofulvin
Nafcillin
Nelfinavir
Norfloxacin
Norfluoxetine
Nevirapine
Oxcarbazepine
Phenylbutazone
Primidone
Progesterone (all progestins)
Rifabutin
Rofecoxib
Sulfadimidine
Sulfinpyrazone
Troglitazone
Rifapentine
Modafinil
Amiodarone
Anastrozole
Clotrimazole
Cyclosporine
Danazol
Delavirdine
Diethyldithiocarbamate
Diltiazem
Dirithromycin
Disulfiram
Entacapone (high dose)
Ethinyl estradiol
Fluoxetine
Fluvoxamine
Gestodene
Indinavir
Isoniazid
Metronidazole
Mibefradil
Miconazole
Nefazodone
Oxiconazole
Paroxetine
Propoxyphene
Roxithromycin
Quinidine
Quinine
Quinupristin and dalfopristin
Ranitidine
Ritonavir
Saquinavir
Sertindole
Sertraline
Troleandomycin
Valproic acid
Verapamil
Voriconazole
Zafirlukast
Zileuton