A Phase I Study of Single Agent OSI-774 (Tarceva) (NSC# 718781, IND# 63383) Followed by OSI-774 With Temozolomide for Patients With Selected Recurrent/Refractory Solid Tumors, Including Brain Tumors
I. Determine the maximum tolerated dose of erlotinib in children with recurrent or
refractory solid tumors.
II. Determine the dose-limiting toxic effects of this drug alone and with temozolomide in
III. Determine the tolerability of this regimen in these patients. IV. Determine the
pharmacokinetics of this regimen in these patients.
I. Determine, preliminarily, the antitumor activity of this regimen in these patients.
OUTLINE: This is a 2-part, multicenter, dose-escalation study of erlotinib. Patients are
stratified according to pretreatment (heavily pretreated [received more than 2 prior
multiagent myelosuppressive chemotherapy regimens OR received prior craniospinal or pelvic
radiotherapy or bone marrow transplantation OR has bone marrow involvement] vs less heavily
Patients receive oral erlotinib once daily on days 1-28. Beginning with course 2, patients
also receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for
up to 23 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of erlotinib during course 1 only 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.
Part 2: Patients receive erlotinib (at the MTD) and temozolomide as in part 1.
PROJECTED ACCRUAL: A total of 9-45 patients (9-24 for part 1 and up to 21 for part 2) will
be accrued for this study.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose-limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
56 days (2 courses)
COG Phase I Consortium
United States: Food and Drug Administration
|COG Phase I Consortium||Arcadia, California 91006-3776|