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A Phase II Study of R115777 (ZARNESTRA) (NSC# 702818, IND# 58359) in Children With Recurrent or Progressive: High Grade Glioma, Medulloblastoma/PNET or Brainstem Glioma

Phase 2
21 Years
Not Enrolling
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

Thank you

Trial Information

A Phase II Study of R115777 (ZARNESTRA) (NSC# 702818, IND# 58359) in Children With Recurrent or Progressive: High Grade Glioma, Medulloblastoma/PNET or Brainstem Glioma


I. 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.

II. 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.

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

- 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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Best objective tumor response rates (complete and partial response), based on MRIs

Outcome Description:

Estimated ultimately as a simple binomial proportion. Estimated actuarially, using the product-limit (PL) estimate.

Outcome Time Frame:

Up to 2 years

Safety Issue:


Principal Investigator

Maryam Fouladi

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

July 2003

Completion Date:

Related Keywords:

  • 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
  • Astrocytoma
  • Glioma
  • Medulloblastoma
  • Oligodendroglioma
  • Neuroectodermal Tumors
  • Neuroectodermal Tumors, Primitive
  • Optic Nerve Glioma



Children's Oncology Group Arcadia, California  91006-3776