Phase I trial to study the effectiveness of combining erlotinib and trastuzumab with paclitaxel in treating patients who have advanced solid tumors. Biological therapies such as erlotinib may interfere with the growth of the tumor cells and slow the growth of the tumor. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib and trastuzumab with paclitaxel may kill more tumor cells
OBJECTIVES: 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 patients. 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 erlotinib. 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 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 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 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Given IV
Given IV
Given orally
Correlative studies
Correlative studies
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
San Antonio, Texas, United States
Maximally tolerated dose (MTD), graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
Time frame: Up to day 28
Response rates, as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: Up to 6 years
Incidence of adverse events, graded according to the NCI CTC v2.0
Time frame: Up to 30 days after last study treatment
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