SCH 66336 in Treating Children With Recurrent or Progressive Brain Tumors

Pediatric Brain Tumor Consortium

Status and phase: Completed; Phase 1

Conditions: Brain and Central Nervous System Tumors

Treatments: Drug: lonafarnib

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00015899

SPRI-P02201

PBTC-003

CDR0000068571

Details and patient eligibility

About

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.

Full 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.

Enrollment: 53 patients

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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