SCH 66336 in Treating Children With Recurrent or Progressive Brain Tumors

Sponsor

Pediatric Brain Tumor Consortium (Other)

Overall Status

Completed

CT.gov ID

NCT00015899

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

61.9

Duration (Months)

5.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Drug: lonafarnib	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

53 participants

Primary Purpose:

Treatment

Official Title:

Phase I Trial Of Escalating Oral Doses Of SCH 66336 In Pediatric Patients With Refractory Or Recurrent Brain Tumors

Study Start Date :

Jan 1, 2002

Actual Primary Completion Date :

Sep 1, 2005

Actual Study Completion Date :

Mar 1, 2007

Outcome Measures

Primary Outcome Measures

Toxicities of SCH 66336 in children and adolescents with refractory CNS cancers []
Maximum tolerated dose of SCH 66336 [Four weeks]
Pharmacokinetics of SCH 66336 []

Secondary Outcome Measures

Tumor response to SCH 66336 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94143-0372
2	Children's National Medical Center	Washington	District of Columbia	United States	20010-2970
3	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
4	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
5	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104-4318
6	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
7	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105-2794
8	Texas Children's Cancer Center	Houston	Texas	United States	77030-2399
9	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington	United States	98105