A Phase I Study of OSI-774 in Combination With Gemcitabine and Radiation in Locally Advanced, Non-Operable Pancreatic Cancer
I. Determine the maximum tolerated dose of erlotinib given concurrently with gemcitabine and
radiotherapy in patients with locally advanced unresectable pancreatic cancer.
I. Determine the toxicity of this regimen in these patients. II. Determine, preliminarily,
the antitumor efficacy of this regimen, in terms of response rate, in these patients.
III. Determine the time to tumor progression and overall survival of patients treated with
OUTLINE: This is a non-randomized, open-label, dose-escalation study of erlotinib.
Chemoradiotherapy: Patients undergo radiotherapy 5 days a week for 5.5 weeks. Beginning on
day 1 and continuing concurrently with radiotherapy, patients receive gemcitabine IV over 30
minutes twice weekly and oral erlotinib once daily. Treatment continues in the absence of
disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of erlotinib 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. Once the MTD is determined, an additional
10 patients receive treatment at that dose.
Patients are radiologically restaged 3-4 weeks after completion of radiotherapy. Patients
with stable or responsive disease proceed to maintenance therapy. Patients whose imaging
studies suggest a potential for curative resection are referred for a surgical evaluation
before initiating maintenance therapy.
Maintenance therapy: Beginning 4-7 weeks after the completion of chemoradiotherapy, patients
receive maintenance chemotherapy comprising gemcitabine IV over 30 minutes on days 1 and 8
and oral erlotinib once daily. Treatment repeats every 21 days for a total of 4 courses in
the absence of disease progression or unacceptable toxicity.
PROJECTED ACCRUAL: A total of 19-28 patients will be accrued for this study.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum-tolerated dose (MTD) of erlotinib hydrochloride based on the incidence of dose-limiting toxicity (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
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