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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00070525
First Posted: October 7, 2003
Last Update Posted: October 8, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
  Purpose
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 Intervention 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

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Best objective tumor response rates (complete and partial response), based on MRIs [ Time Frame: 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 Frame: 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 Frame: 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 Frame: 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 [ Time Frame: Up to 2 years ]

Estimated Enrollment: 90
Study Start Date: November 2003
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

OBJECTIVES:

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00070525


Locations
United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Maryam Fouladi Children's Oncology Group
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00070525     History of Changes
Other Study ID Numbers: NCI-2012-01806
NCI-2012-01806 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000334862
COG-ACNS0226
ACNS0226 ( Other Identifier: Children's Oncology Group )
ACNS0226 ( Other Identifier: CTEP )
U10CA098543 ( U.S. NIH Grant/Contract )
First Submitted: October 3, 2003
First Posted: October 7, 2003
Last Update Posted: October 8, 2013
Last Verified: October 2013

Additional relevant MeSH terms:
Glioma
Astrocytoma
Oligodendroglioma
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Medulloblastoma
Optic Nerve Glioma
Neoplasms, Neuroepithelial
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Optic Nerve Neoplasms
Cranial Nerve Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Peripheral Nervous System Neoplasms
Cranial Nerve Diseases
Nervous System Diseases
Optic Nerve Diseases
Eye Diseases
Tipifarnib
Antineoplastic Agents