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. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether cetuximab is more effective when given alone or together with sorafenib tosylate in treating patients with head and neck cancer. This randomized phase II trial is studying cetuximab to see how well it works when given together with or without sorafenib tosylate in treating patients with refractory, recurrent, and/or metastatic head and neck cancer.
PRIMARY OBJECTIVES: I. Compare the progression free survival (PFS) of the combination of cetuximab and sorafenib to that of cetuximab alone in patients with recurrent, refractory or metastatic squamous cell carcinoma of the head and neck (SCCHN). SECONDARY OBJECTIVES: I. To evaluate the response rate, overall survival (OS) and toxicity of the combination of cetuximab and sorafenib and of cetuximab alone. II. To evaluate the presence of EGFRvIII mutation, increased EGFR gene copy number and activated EGFR gene expression signature, and correlate with clinical parameters (RR, OS and PFS) in the cetuximab alone and cetuximab/sorafenib arms. III. To evaluate whether VEGF receptor family and their ligand expression can predict response to cetuximab/sorafenib. IV. To determine the proteomic profiles in serum and tumors that can predict the response and survival upon the treatment with cetuximab or cetuximab/sorafenib. V. To evaluate the effect of therapy on both general and head and neck specific functionality, symptom burden and QOL. OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 and oral placebo twice daily on days 1-21. (oral placebo closed as of 02/18/2010). ARM II: Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 and oral sorafenib tosylate twice daily on days 1-21. In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Paraffin embedded tissue samples are collected at baseline for pharmacogenomic studies and blood samples are collected at baseline and for the first 3 courses for research purposes. Quality of life and symptom burden are assessed by Vanderbilt Head and Neck Symptom Survey, FACT-HN, and Fatigue and Pain Inventory questionnaires at baseline, at day 43, and at 3 and 6 months. After completion of study treatment, patients are followed periodically for 3 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
55
Given IV
Given orally
Given orally
Correlative studies
Ancillary studies
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Suburban Hospital
Bethesda, Maryland, United States
Billings Clinic
Billings, Montana, United States
Montefiore Medical Center
The Bronx, New York, United States
University of North Carolina
Chapel Hill, North Carolina, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States
Progression Free Survival (PFS)
Estimated probable duration of life without disease progression, from on-study date to earlier of progression date or date of death from any cause, using the Kaplan-Meier method with censoring (see analysis population description for additional details). Disease progression is defined under Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as \>=20% increase in sum of longest diameters of target lesions, unequivocal progression of non-target lesions, or appearance of new lesions.
Time frame: On-study date to lesser of date of progression or date of death from any cause (assessed up to 3 years)
Best Response
Number of patients in each response category, per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, summarized as follows for target lesion criteria (see RECIST v1.1 for additional details): complete response (CR),disappearance of target lesions; partial response (PR), \>=30% decrease in sum of longest diameter of target lesions; progressive disease (PD), \>=20% increase in sum of longest diameter (LD) of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or SD. Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR\>PR\>SD\>PD.
Time frame: On-treatment date to date of disease progression (assessed up to 3 years)
Overall Survival (OS)
Estimated probable duration of life from on-study date to date of death from any cause, using the Kaplan-Meier method with censoring (see analysis population description for additional details)
Time frame: On-study date to date of death from any cause (assessed up to 3 years)
Number of Participants With Each Worst-Grade Toxicity
Count of patients according to the worst-grade toxicity experienced by each, where worst-grade toxicity is per NCI common toxicity criteria: grade 1, mild; grade 2, moderate; grade 3, severe; grade 4, life-threatening; grade 5, death
Time frame: On-study date to 30 days following final dose of study drug
Gene Expression Levels
Formalin-fixed, paraffin-embedded (FFPE) tumors were collected. The FFPE tumors were to be evaluated for p16 expression using immunohistochemistry staining with antibody. Gene Expression Levels (positive when \>70% cells stained, otherwise negative) were to be described using frequencies.
Time frame: Pre-therapy
Overall Survival Associated With Immunomodulatory Cytokines
Twelve immunomodulatory cytokines were selected based on previous a feasibility study and detected using multiplex Luminex bead assays from patient's plasma. One cytokines, HGF, was eliminated due to extremely low expression. Three representative cytokines, TGF-beta 1, IL-8 and VEGF were to be evaluated for association with survival due to clustering.
Time frame: Pre-therapy, up to about 42 months (follow-up for overall survival)
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