Erlotinib and Cetuximab in Treating Patients With Advanced Solid Tumors With Emphasis on Non-Small Cell Lung Cancer
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.
Unspecified Adult Solid Tumor, Protocol Specific
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Erlotinib (TARCEVA) and Cetuximab (ERBITUX) in Advanced Solid Tumors, With Emphasis on Non Small Cell Lung Cancer (NSCLC)|
- Toxicity [ Time Frame: Toxicity will be assessed on day 8, 15, 22 and subsequently at the beginning of every cycle. ] [ Designated as safety issue: Yes ]Toxicity will be evaluated based on the standard NCI CTCAE V.3.0 grading criteria.
- Response Rate [ Time Frame: CT scans will be performed at baseline and every two cycles (prior to 3rd and 5th cycle). ] [ Designated as safety issue: No ]Response rate will be assessed by CT scan.
|Study Start Date:||August 2006|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
|Experimental: Erlotinib + Cetuximab||
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.
Other Name: ErbituxDrug: erlotinib
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.
Other Name: Tarceva
- 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)
- 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00408499
|United States, California|
|University of California Davis Cancer Center|
|Sacramento, California, United States, 95817|
|Study Chair:||David R. Gandara, MD||University of California, Davis|