Erlotinib and Cetuximab in Treating Patients With Advanced Solid Tumors With Emphasis on Non-Small Cell Lung Cancer

Phase 1

Completed

Conditions: Lung Cancer
Unspecified Adult Solid Tumor, Protocol Specific

Interventions: Drug: cetuximab
Drug: erlotinib

Registration Number: NCT00408499

Lead Sponsor: University of California, Davis

Brief Summary: RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving erlotinib together with cetuximab may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of erlotinib and cetuximab and to see how well they work in treating patients with advanced solid tumors or progressive or recurrent stage III or stage IV non-small cell lung cancer.

Detailed Description: 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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 64

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Erlotinib + Cetuximab	erlotinib	Daily erlotinib combined with weekly cetuximab
Erlotinib + Cetuximab	cetuximab	Daily erlotinib combined with weekly cetuximab

Primary Outcome Measures

Name	Time	Method
Number of Patients Experiencing a DLT	baseline through cycle 1 of treatment	Patients will be followed during cycle 1 for the occurrence of a protocol defined dose limiting toxicity
Number of Patients Correlated With Best Overall Response.	Every two cycles from first dose to last dose of study drugs	To determine the efficacy, as measured by objective tumor response rate (RICIST criteria), of daily oral erlotinib and weekly intravenous cetuximab in patients with advanced NSCLC. Best overall response per patient will be reported below.

Secondary Outcome Measures

Name	Time	Method
Patient Outcome	Patients will be followed until death	In the Phase II portion of the study, patients will be followed for both disease free progression by capturing disease progression date and for over all survival by capturing death date.