Phase I Study To Determine The Safety, Tolerance And Preliminary Antineoplastic Activity Of Combined EGFR (erbB1) And HER2 (erbB2) Blockade, With OSI-774 And Trastuzumab, In Combination With Weekly Paclitaxel
I. Determine the safety, quantitative and qualitative toxic effects, maximum tolerated dose,
and dose-limiting toxic effects of erlotinib when combined with paclitaxel and trastuzumab
(Herceptin) in patients with advanced solid tumors.
II. Determine the relevant pharmacokinetic interactions between these agents in these
III. Determine, preliminarily, the antitumor activity of this regimen in these patients.
OUTLINE: This is an open-label, non-randomized, multicenter, dose-escalation study of
Intermittent schedule: Patients receive paclitaxel IV over 1 hour followed 30 minutes later
by trastuzumab (Herceptin) IV over 30 minutes on days 1, 8, and 15 of each course. Patients
also receive oral erlotinib once daily on days 3-28 of course 1 and on days 1-28 of
subsequent courses. Courses repeat every 28 days in the absence of disease progression or
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 at least 2
of 3 or 2 of 6 patients experience dose-limiting toxicity.
Continuous schedule: Once the MTD is determined using the intermittent schedule, an
additional 12 patients are accrued to study the tolerability of a continuous schedule
comprising paclitaxel and trastuzumab as above on days 1, 8, 15, and 22 and oral erlotinib
once daily on days 3-28 during course 1 and on days 1-28 of subsequent courses using the
same dose-escalation scheme as above. Courses repeat as above.
Patients are followed every 30 days.
PROJECTED ACCRUAL: A maximum of 40 patients will be accrued for this study within 10-13.3
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximally tolerated dose (MTD), graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
Up to day 28
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
United States: Food and Drug Administration
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