Erlotinib and Cetuximab in Treating Patients With Advanced Solid Tumors or Progressive or Recurrent Stage III or Stage IV Non-Small Cell Lung Cancer

OBJECTIVES:

Primary

- 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.
(Phase II)

Secondary

- 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.
(Phase I)

- 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.
(Phase II)

- 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
predictive response.

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
periodically.

PROJECTED ACCRUAL: A total of 62 patients will be accrued for this study