Philadelphia, Pennsylvania 19104

  • Brain and Central Nervous System Tumors

Purpose:

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.


Study summary:

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.


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


Study is Available At:


Original ID:

CDR0000068571


NCT ID:

NCT00015899


Secondary ID:

PBTC-003


Study Acronym:


Brief Title:

SCH 66336 in Treating Children With Recurrent or Progressive Brain Tumors


Official Title:

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


Overall Status:

Completed


Study Phase:

Phase 1


Genders:

Both


Minimum Age:

N/A


Maximum Age:

21 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Pediatric Brain Tumor Consortium


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Endpoint Classification: Safety Study, Primary Pu


Number of Arms:

0


Number of Groups:

0


Total Enrollment:

53


Enrollment Type:

Actual


Overall Contact Information

Official Name:Mark W. Kieran, MD, PhD
Study Chair
Dana-Farber Cancer Institute

Study Dates

Start Date:January 2002
Completion Date:March 2007
Completion Type:Actual
Primary Completion Date:September 2005
Primary Completion Type:Actual
Verification Date:October 2009
Last Changed Date:October 13, 2009
First Received Date:May 6, 2001

Study Outcomes

Outcome Type:Primary Outcome
Measure:Toxicities of SCH 66336 in children and adolescents with refractory CNS cancers
Safety Issues:True
Outcome Type:Primary Outcome
Measure:Maximum tolerated dose of SCH 66336
Time Frame:Four weeks
Safety Issues:True
Outcome Type:Primary Outcome
Measure:Pharmacokinetics of SCH 66336
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Tumor response to SCH 66336
Safety Issues:False

Study Interventions

Intervention Type:Drug
Name:lonafarnib
Other Name:SCH 66336

Study Arms

There are no available Study Arms

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Pediatric Brain Tumor Consortium
Agency Class:NIH
Agency Type:Collaborator
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Results Reference
Citation: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.
PMID:17634493

Data Source: ClinicalTrials.gov

Date Processed: April 03, 2020

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