Clinical trial NCT00408499
Conditions: Lung Cancer Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific stage IIIA non-small cell lung cancer stage IIIB non-small cell lung cancer stage IV non-small cell lung cancer recurrent non-small cell lung cancer
Sponsor: University of California, Davis
Start date: 2006-08-01; Completion date: 2013-01-01
Enrollment: 64 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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

Arms: arm 1: Daily erlotinib combined with weekly cetuximab
Interventions: intervention 1: cetuximab intervention 2: erlotinib
Intervention descriptions: intervention 1: Cetuximab will be administered intravenously weekly at the maximum tolerated dose (determined in Phase I portion of the study) on a 28 day cycle. Participants will be in this study for at least 2 cycles (8 weeks). If the evaluations show that this treatment has been effective against the participant's cancer, he/she will continue the therapy. intervention 2: Erlotinib will be taken by mouth daily on a 28 day cycle. It is in tablet form. The dose will be determined in Phase I portion of the study. Participants will be in this study for at least 2 cycles (8 weeks). If the evaluations show that this treatment has been effective against the participant's cancer, he/she will continue the therapy.

Protocol documents: