Phase I/II Study of Docetaxel and OSI-774 (Erlotinib) in Solid Tumor Patients With an Emphasis on NSCLC Using Molecular Correlates as Potential Markers of Response
OBJECTIVES:
Primary
- Determine the safety and feasibility of two different schedules of erlotinib
hydrochloride and docetaxel in patients with advanced solid tumors. (Phase I [completed
as of 12/01/2004])
- Determine the response rate in patients with advanced non-small cell lung cancer
treated with second-line docetaxel and erlotinib hydrochloride. (Phase II)
Secondary
- Compare the toxicity of two different schedules of erlotinib hydrochloride and
docetaxel in these patients. (Phase I [completed as of 12/01/2004])
- Determine the maximum tolerated dose of two different schedules of erlotinib
hydrochloride and docetaxel. (Phase I [completed as of 12/01/2004])
- Assess the overall survival and progression-free survival. (Phase II)
- Determine the frequency and severity of toxicities associated with this treatment
regimen. (Phase II)
Tertiary
- Perform laboratory correlative studies on patient tissue and blood samples to
investigate potential predictors of response.
OUTLINE: This is a phase I, dose-escalation study of erlotinib hydrochloride (phase I
completed as of 12/01/2004) followed by a phase II, open-label study.
- Phase I (completed as of 12/01/2004): Patients will be assigned in alternating fashion
to 1 of 2 treatment groups.
- Group I: Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib
hydrochloride once on days 2, 9, and 16.
- Group II: Patients receive docetaxel as in group I and oral erlotinib
hydrochloride once daily on days 2-16.
In both groups, treatment repeats every 21 days for up to 6 courses in the absence of
unacceptable toxicity or disease progression. Patients may then continue to receive
erlotinib hydrochloride alone in the absence of unacceptable toxicity or disease
progression.
In both groups, cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride
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.
- Phase II: Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib
hydrochloride at the MTD determined in group II of phase I once daily on days 2-16.
Treatment repeats every 21 days for up to 6 courses in the absence of disease
progression or unacceptable toxicity. Patients may then continue to receive erlotinib
hydrochloride alone in the absence of disease progression or unacceptable toxicity.
Blood samples, buccal mucosal cells, and tumor tissue are obtained before and after
treatment. Epidermal growth factor receptor (EGFR) expression and polymorphisms and p27
protein expression are assessed by immunohistochemistry. Immunofluorescence (by
laser-scanning cytometry) is used to detect EGFR and p27.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 87 patients will be accrued for this study.
Interventional
Allocation: Non-Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety and toxicity of erlotinib hydrochloride and docetaxel as measured by NCI CTC v3.0 on day 8 of course 1 and on day 1 of every subsequent course (Phase I [completed as of 12/01/2004])
12/01/2004
Yes
David R. Gandara, MD
Study Chair
University of California, Davis
United States: Food and Drug Administration
CDR0000505821
NCT00390429
July 2002
August 2012
Name | Location |
---|---|
University of California Davis Cancer Center | Sacramento, California 95817 |