PBTC-003 Abstract for Health Professionals

PBTC-003 Abstract for Health Professionals

Study Title: Phase I Trial of Escalating Oral Doses of SCH 66336 in Pediatric Patients with Refractory or Recurrent Brain Tumors

Description:

This is a phase I trial for patients 21 years of age or less, with recurrent or progressive brain tumors. It is a collaborative study of the Pediatric Brain Tumor Consortium.

SCH 66336 will be given twice daily without breaks, approximately every 12 hours. A course is defined as 4 weeks of therapy, for a total of 13 courses (one year). Patients on enzyme inducing anticonvulsant drugs (EIACD) are not eligible.

SCH 66336 Dose Escalation Table – Doses given BID
Dose Level	Dose (mg/m²)	Daily Dose (mg/m²)
1	90	180
2	115	230
3	150	300
4	200	400
5	260	520

Objectives:

To establish the qualitative and quantitative toxicity of SCH 66336 when administered to children and adolescents with a refractory CNS malignancy.

To establish the maximum-tolerated dosage (MTD) of SCH 66336.

To investigate which clinical and laboratory studies are needed to monitor or alter therapy to prevent unacceptable toxicity.

To describe the pharmacokinetics of SCH 66336 with this route of administration.

To describe the activity of SCH 66336 with this route of administration using in vitro assays of patient white blood cell farnesyl transferase inhibition and inhibition of prelamin A farnesylation in buccal mucosa cells.

To obtain preliminary information about the efficacy of SCH 66336.

Eligibility Criteria:

Patient must be <= 21 years of age.

All patients with malignant recurrent or progressive brain tumors will be eligible. All patients must have a pathologic diagnosis either from their initial presentation, or at the time of recurrence or progression. The requirement for histologic verification may be waived for patients with brainstem gliomas.

Patient must be able to swallow pills.

Karnofsky/Lansky >= 60%; life expectancy > 8 weeks.

Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to study entry.

Greater than 3rd percentile weight for height; Albumin > 3g/dl.

Evidence of recovery from prior chemotherapy. No myelosuppressive chemotherapy within 3 weeks (6 weeks if a nitrosourea agent) prior to study entry.

Contact:

Study Chair	Study Co-Chair
Kieran, Mark W., MD, PhD Dana-Farber Cancer Institute Department of Pediatrics 44 Binney Street Boston, MA 02115	Packer, Roger, MD Children's National Medical Center Department of Neurology 111 Michigan Avenue, NW Washington, DC 20010