A Phase 1 Study of SAHA (NSC# 701852 IND#71976) in Pediatric Patients With Recurrent or Refractory Solid Tumors (Including Lymphomas) and Leukemia Followed by a Phase I Study of SAHA in Combination With 13-Cis-Retinoic Acid for Patients With Selected Recurrent/Refractory Solid Tumors
I. Determine the maximum tolerated dose (MTD) of vorinostat (SAHA) in young patients with
recurrent or refractory solid tumors or lymphomas.
II. Determine the MTD of SAHA administered in combination with isotretinoin in young
patients with recurrent or refractory neuroblastoma, medulloblastoma/CNS primitive
neuroectodermal tumor, or atypical teratoid rhabdoid tumor.
III. Determine the tolerability of the solid tumor MTD of SAHA in young patients with
recurrent or refractory leukemia.
IV. Determine the toxic effects of SAHA administered with or without isotretinoin in these
V. Determine the pharmacokinetics of this drug in these patients.
I. Determine, preliminarily, the antitumor activity of SAHA administered with or without
isotretinoin in these patients.
II. Correlate the pharmacokinetics of this drug with genetic polymorphisms (e.g., UGT1A1) in
OUTLINE: This is a multicenter, dose-escalation study of vorinostat (SAHA).
Group 1 (solid tumor or lymphoma patients): Patients receive oral SAHA once daily on days
1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease
progression or unacceptable toxicity.Cohorts of 3-6 patients receive escalating doses of
SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An
additional 6 patients may be treated at the MTD.
Group 2 (leukemia patients): Patients receive SAHA as in group 1 at the MTD.
Group 3 (select solid tumor patients): Patients receive oral isotretinoin twice daily on
days 1-14. Patients also receive SAHA once daily on days 1-28 OR once on days 1, 3, 5, 8,
10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 12 courses in
the absence of disease progression or unacceptable toxicity.The MTD of SAHA is determined as
in group 1. An additional 6 patients may be treated at the MTD.
After completion of study treatment, patients are followed periodically.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD) defined as the maximum dose at which fewer than one-third of patients experience dose-limiting toxicities DLT graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Children's Oncology Group
United States: Food and Drug Administration
|Children's Oncology Group||Arcadia, California 91006-3776|