Phase I/II Study of Erlotinib (TARCEVA) and Cetuximab (ERBITUX) in Advanced Solid Tumors, With Emphasis on Non Small Cell Lung Cancer (NSCLC)
- Determine the safety and feasibility of erlotinib hydrochloride and cetuximab in
patients with advanced solid tumors. (Phase I)
- Determine the efficacy of this regimen, in terms of objective tumor response rate, in
patients with advanced non-small cell lung cancer (NSCLC) pre-treated with platinum.
- Determine the maximum tolerated dose of this regimen in these patients. (Phase I)
- Determine the efficacy of this regimen, in terms of response rate, in these patients.
- Determine the progression-free and overall survival of patients treated with this
regimen. (Phase II)
- Determine the frequency and severity of toxicities of this regimen in these patients.
- Determine epidermal growth factor receptor (EGFR) and K-RAS mutation status. (Phase II)
- Evaluate EGFR protein expression and protein expression of downstream markers (e.g.,
pMAPK, pAKT, p27, and Ki-67). (Phase II)
- Evaluate the levels of marker proteins (e.g., pMAPK, pAKT, p27, and Ki-67) in buccal
cells. (Phase II)
- Determine gene copy number by EGFR fluorescent in situ hybridization (FISH). (Phase II)
- Identify EGFR polymorphisms by analysis of genomic DNA from peripheral blood
mononuclear cells. (Phase II)
- Determine if the continued presence or absence of mutant K-RAS tumor DNA correlates
with response and/or outcome. (Phase II)
OUTLINE: This is a phase I, dose-escalation study followed by an open-label, phase II study.
- Phase I: Patients receive oral erlotinib hydrochloride once daily on days 1-28 and
cetuximab IV over 1-2 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days
in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride and cetuximab
until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which ≥ 2 of 6 patients experience dose-limiting toxicity. At least 6
patients are treated at the MTD.
- Phase II: Patients receive erlotinib hydrochloride and cetuximab at the MTD determined
in phase I.
Blood and buccal samples are acquired from patients at baseline and prior to courses 2 and
3. Samples are examined by fluorescent in situ hybridization (FISH), immunohistochemistry,
polymorphism analysis, and protein expression assays to assess molecular markers (epidermal
growth factor receptor, K-RAS, pMAPK, pAKT, p27 and Ki-67) for biologic effects and
After completion of phase I treatment, patients are followed for 30 days or until all
toxicities resolve. After completion of phase II treatment, patients are followed
PROJECTED ACCRUAL: A total of 62 patients will be accrued for this study
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Toxicity will be evaluated based on the standard NCI CTCAE V.3.0 grading criteria.
Toxicity will be assessed on day 8, 15, 22 and subsequently at the beginning of every cycle.
David R. Gandara, MD
University of California, Davis
United States: Food and Drug Administration
|University of California Davis Cancer Center||Sacramento, California 95817|