SCH 66336 in Treating Children With Recurrent or Progressive Brain Tumors - Full Text View

Sponsor:	Pediatric Brain Tumor Consortium
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier:	NCT00015899

Purpose

RATIONALE: SCH 66336 may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of SCH 66336 in treating children with recurrent or progressive brain tumors.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: lonafarnib	Phase I

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Primary Purpose: Treatment
Official Title:	Phase I Trial Of Escalating Oral Doses Of SCH 66336 In Pediatric Patients With Refractory Or Recurrent Brain Tumors

Resource links provided by NLM:

MedlinePlus related topics: Brain Cancer Cancer Childhood Brain Tumors

Drug Information available for: Lonafarnib

U.S. FDA Resources

Further study details as provided by Pediatric Brain Tumor Consortium:

Primary Outcome Measures:

Toxicities of SCH 66336 in children and adolescents with refractory CNS cancers [ Designated as safety issue: Yes ]
Maximum tolerated dose of SCH 66336 [ Time Frame: Four weeks ] [ Designated as safety issue: Yes ]
Pharmacokinetics of SCH 66336 [ Designated as safety issue: No ]

Secondary Outcome Measures:

Tumor response to SCH 66336 [ Designated as safety issue: No ]

Enrollment:	53
Study Start Date:	January 2002
Study Completion Date:	March 2007
Primary Completion Date:	September 2005 (Final data collection date for primary outcome measure)

Intervention Details:

Other Name: SCH 66336

Detailed Description:

OBJECTIVES:

Determine the qualitative and quantitative toxicity of SCH 66336 in children with recurrent or progressive brain tumors.
Estimate the maximum tolerated dose of this drug in these patients.
Describe the pharmacokinetics of this drug with and without dexamethasone in these patients.
Investigate the efficacy of this drug in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive oral SCH 66336 twice daily. Treatment repeats every 4 weeks for a total of 26 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-6 patients receive escalating doses of SCH 66336 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which it is predicted that 20% of patients may experience dose-limiting toxicity. An additional 6 patients are treated at the determined MTD.

Patients are followed within 30 days of the last administration of the study drug and then for up to 3 months.

PROJECTED ACCRUAL: Approximately 25 patients will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed recurrent or progressive (refractory) brain tumors
- Histologic confirmation waived for brainstem gliomas
Bone marrow involvement allowed if transfusion independent

PATIENT CHARACTERISTICS:

Age:

21 and under

Performance status:

Lansky 60-100% OR
Karnofsky 60-100%

Life expectancy:

More than 8 weeks

Hematopoietic:

See Disease Characteristics
Absolute neutrophil count greater than 1,000/mm^3
Platelet count greater than 75,000/mm^3
Hemoglobin greater than 9 g/dL

Hepatic:

Bilirubin no greater than upper limit of normal
SGPT and SGOT less than 2.5 times normal
Albumin greater than 3 g/dL
PT/PTT no greater than 120% upper limit of normal
No overt hepatic disease

Renal:

Creatinine no greater than 1.5 times normal OR
Glomerular filtration rate greater than 70 mL/min
No overt renal disease

Cardiovascular:

No overt cardiac disease

Pulmonary:

No overt pulmonary disease

Other:

Neurologic deficits allowed if stable for at least 1 week prior to study
More than 3rd percentile weight for height
Able to swallow pills
No uncontrolled infection
No known or suspected allergy to poloxamer 188, croscarmellose sodium, silicon dioxide, or magnesium stearate I
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for up to 10 weeks after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

More than 6 months since prior bone marrow transplantation
More than 1 week since prior growth factors

Chemotherapy:

At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered

Endocrine therapy:

Concurrent dexamethasone allowed if on stable dose for at least 1 week prior to study
Concurrent oral contraceptives or other hormonal contraceptive methods allowed

Radiotherapy:

More than 6 weeks since prior substantial bone marrow radiotherapy
More than 3 months since prior craniospinal radiotherapy (more than 24 Gy) or total body irradiation
More than 2 weeks since prior focal radiotherapy for symptomatic metastatic sites

Surgery:

Not specified

Other:

No concurrent enzyme-inducing anticonvulsant drugs
No other concurrent anticancer or experimental drug therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00015899

Locations

United States, California
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94143-0372
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-4318
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105-2794
United States, Texas
Texas Children's Cancer Center
Houston, Texas, United States, 77030-2399
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105

Sponsors and Collaborators

Pediatric Brain Tumor Consortium

National Cancer Institute (NCI)

Investigators

Study Chair:

Mark W. Kieran, MD, PhD

Dana-Farber Cancer Institute

More Information

Additional Information:

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

Publications:

Kieran MW, Packer RJ, Onar A, Blaney SM, Phillips P, Pollack IF, Geyer JR, Gururangan S, Banerjee A, Goldman S, Turner CD, Belasco JB, Broniscer A, Zhu Y, Frank E, Kirschmeier P, Statkevich P, Yver A, Boyett JM, Kun LE. Phase I and pharmacokinetic study of the oral farnesyltransferase inhibitor lonafarnib administered twice daily to pediatric patients with advanced central nervous system tumors using a modified continuous reassessment method: a Pediatric Brain Tumor Consortium Study. J Clin Oncol. 2007 Jul 20;25(21):3137-43.

Responsible Party:	James M. Boyett/PBTC Operations and Biostatistics Center Executive Director, Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier:	NCT00015899 History of Changes
Other Study ID Numbers:	CDR0000068571, PBTC-003, SPRI-P02201
Study First Received:	May 6, 2001
Last Updated:	October 13, 2009
Health Authority:	United States: Food and Drug Administration

Keywords provided by Pediatric Brain Tumor Consortium:

childhood craniopharyngioma
childhood central nervous system germ cell tumor
childhood oligodendroglioma
childhood choroid plexus tumor
childhood grade I meningioma
childhood grade II meningioma
childhood grade III meningioma

recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
recurrent childhood medulloblastoma
recurrent childhood visual pathway and hypothalamic glioma
recurrent childhood ependymoma
childhood atypical teratoid/rhabdoid tumor
childhood spinal cord neoplasm

Additional relevant MeSH terms:

Brain Neoplasms
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site

Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on February 12, 2012