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

Sponsors and Collaborators:	Children's Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00070525

Purpose

RATIONALE: Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

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.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: tipifarnib	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: R 115777 Tipifarnib

U.S. FDA Resources

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

Primary Outcome Measures:

Objective tumor response (complete and partial response) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time-to-treatment failure [ Designated as safety issue: No ]
Time-to-progression [ Designated as safety issue: No ]
Time-to-death [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]

Study Start Date:

November 2003

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.

PROJECTED ACCRUAL: A total of 90 patients (30 per stratum) will be accrued for this study within 1-3 years.

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed brain tumor, including the following:
- Anaplastic astrocytoma
- Glioblastoma multiforme
- Gliosarcoma
- Anaplastic oligodendroglioma
- Medulloblastoma/primitive neuroectodermal tumor (PNET)
- Diffuse intrinsic brain stem glioma* NOTE: *Histologic confirmation waived for brain stem glioma
Progressive or relapsed disease after prior conventional therapy
Radiographic evidence of measurable disease

PATIENT CHARACTERISTICS:

Age

21 and under

Performance status

Karnofsky 60-100% (over 16 years of age)
Lansky 60-100% (16 years of age and under) OR
ECOG 0-2

Life expectancy

At least 8 weeks

Hematopoietic

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)

Hepatic

Bilirubin no greater than 1.5 times upper limit of normal (ULN)
SGPT and SGOT less than 2.5 times ULN

Renal

Creatinine clearance OR radioisotope glomerular filtration rate at least 70 mL/min OR
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)

Cardiovascular

Shortening fraction at least 27% by echocardiogram OR
Ejection fraction at least 50% by MUGA

Pulmonary

No dyspnea at rest
No exercise intolerance
Pulse oximetry greater than 94%* NOTE: *If determination is clinically indicated

Other

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)

PRIOR CONCURRENT THERAPY:

Biologic therapy

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

Chemotherapy

More than 2 weeks since prior myelosuppressive chemotherapy (4-6 weeks for nitrosoureas or temozolomide) and recovered
No concurrent anticancer chemotherapy

Endocrine therapy

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

Radiotherapy

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

Surgery

Not specified

Other

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
- Cimetadine
- 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00070525

Show 231 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Maryam Fouladi, MD	Children's Hospital Medical Center, Cincinnati
Investigator:	Ian F. Pollack, MD	Children's Hospital of Pittsburgh

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Fouladi M, Nicholson HS, Zhou T, Laningham F, Helton KJ, Holmes E, Cohen K, Speights RA, Wright J, Pollack IF. A phase II study of the farnesyl transferase inhibitor, tipifarnib, in children with recurrent or progressive high-grade glioma, medulloblastoma/primitive neuroectodermal tumor, or brainstem glioma: A children's oncology group study. Cancer. 2007 Oct 11; [Epub ahead of print]

Study ID Numbers:	CDR0000334862, COG-ACNS0226
Study First Received:	October 3, 2003
Last Updated:	August 23, 2008
ClinicalTrials.gov Identifier:	NCT00070525 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

childhood high-grade cerebral astrocytoma
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
recurrent childhood brain stem glioma

childhood oligodendroglioma
recurrent childhood supratentorial primitive neuroectodermal tumor
recurrent childhood visual pathway and hypothalamic glioma
recurrent childhood medulloblastoma

Study placed in the following topic categories:

Neuroectodermal Tumors, Primitive
Astrocytoma
Central Nervous System Neoplasms
Recurrence
Neuroectodermal Tumors
Brain Stem Glioma, Childhood
Neoplasms, Germ Cell and Embryonal

Medulloblastoma
Neuroepithelioma
Oligodendroglioma
Glioma
Nervous System Neoplasms
Tipifarnib
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neuroectodermal Tumors, Primitive
Neoplasms by Histologic Type
Antineoplastic Agents
Nervous System Diseases
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Pharmacologic Actions
Neuroectodermal Tumors
Neoplasms

Neoplasms by Site
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Medulloblastoma
Glioma
Neoplasms, Neuroepithelial
Nervous System Neoplasms
Tipifarnib
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on September 03, 2009