SCH 66336 in Treating Children With Recurrent or Progressive Brain Tumors

Brain and Central Nervous System Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00015899
• Other study ID #: CDR0000068571
• Secondary ID: PBTC-003SPRI-P02
• Status: Completed
• Phase: Phase 1
• First received: May 6, 2001
• Last updated: October 13, 2009
• Start date: January 2002
• Est. completion date: March 2007

Study information

• Verified date: October 2009
• Source: Pediatric Brain Tumor Consortium
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: March 2007
• Est. primary completion date: September 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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 Design

Endpoint Classification: Safety Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

Drug:
• lonafarnib

Locations

Country	Name	City	State
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	Texas Children's Cancer Center	Houston	Texas
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Pediatric Brain Tumor Consortium	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 o — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicities of SCH 66336 in children and adolescents with refractory CNS cancers			Yes
Primary	Maximum tolerated dose of SCH 66336		Four weeks	Yes
Primary	Pharmacokinetics of SCH 66336			No
Secondary	Tumor response to SCH 66336			No