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

PURPOSE: Phase I trial to study the effectiveness of SCH 66336 in treating children who have recurrent or progressive brain tumors.

Condition	Treatment or Intervention	Phase
childhood brain tumor childhood meningioma childhood rhabdoid tumor of the central nervous system childhood spinal cord tumors	Drug: lonafarnib  Procedure: enzyme inhibitor therapy	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the qualitative and quantitative toxicity of SCH 66336 in children with recurrent or progressive brain tumors.
• Determine the maximum tolerated dose of this drug in these patients.
• Determine the pharmacokinetics of this drug with and without dexamethasone in these patients.
• Determine 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 13 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.

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

Ages Eligible for Study:  up to  21 Years,  Genders Eligible for Study:  Both

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

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

Study chairs or principal investigators

Mark William Kieran, MD,  Study Chair,  Dana-Farber/Harvard Cancer Center   

Study ID Numbers:  CDR0000068571; PBTC-003; SPRI-P02201
Record last reviewed:  September 2004
Last Updated:  October 13, 2004
Record first received:  May 6, 2001
ClinicalTrials.gov Identifier:  NCT00015899
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08