SCH 66336 in Treating Children With Recurrent or Progressive Brain Tumors

NCT ID: NCT00015899

Last Updated: 2009-10-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-01-31
• Study Completion Date: 2007-03-31

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.

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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Primary Study Purpose: TREATMENT

Interventions

lonafarnib

Intervention Type: DRUG

Other Intervention Names

SCH 66336

Eligibility Criteria

Inclusion 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

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Pediatric Brain Tumor Consortium

NETWORK

Sponsor Role: lead

Responsible Party

Pediatric Brain Tumor Consortium

Principal Investigators

Mark W. Kieran, MD, PhD

Role: STUDY_CHAIR

Dana-Farber Cancer Institute

Locations

UCSF Comprehensive Cancer Center

San Francisco, California, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Texas Children's Cancer Center

Houston, Texas, United States

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Countries

United States

References

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. doi: 10.1200/JCO.2006.09.4243.

Reference Type: RESULT

PMID: 17634493 (View on PubMed)

Other Identifiers

PBTC-003

Identifier Type: -

Identifier Source: secondary_id

SPRI-P02201

Identifier Type: -

Identifier Source: secondary_id

CDR0000068571

Identifier Type: -

Identifier Source: org_study_id