Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

SCH 66336 in Treating Children With Recurrent or Progressive Brain Tumors

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed 21 and under NCI PBTC-003 SPRI-P02201, NCT00015899

Objectives

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

Entry Criteria

Disease Characteristics:

• Histologically confirmed recurrent or progressive (refractory) brain tumors
  • Histologic confirmation waived for brainstem gliomas



• Bone marrow involvement allowed if transfusion independent

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

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/mm³
• Platelet count greater than 75,000/mm³
• 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

Expected Enrollment

Approximately 25 patients will be accrued for this study.

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 and then for up to 3 months.

Kieran MW, Packer RJ, Onar A, et al.: 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 25 (21): 3137-43, 2007.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Pediatric Brain Tumor Consortium

Mark Kieran, MD, PhD, Protocol chair		Ph: 617-632-4907; 866-790-4500

Registry Information
Official Title		Phase I Trial Of Escalating Oral Doses Of SCH 66336 In Pediatric Patients With Refractory Or Recurrent Brain Tumors
Trial Start Date		2002-01-08
Registered in ClinicalTrials.gov		NCT00015899
Date Submitted to PDQ		2001-03-01
Information Last Verified		2004-07-26
NCI Grant/Contract Number		CA81457

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