Clinical Trials

PRIMARY OBJECTIVES: I. Response rate. We will compare the cetuximab/ARQ 197 (tivantinib) combination with cetuximab single agent activity. SECONDARY OBJECTIVES: I. Continuous tumor shrinkage. II. Progression-free survival (PFS). III. Overall survival (OS). IV. Endpoints I), II), and III) above, as well as response rates, will be assessed and compared between treatment arms in the subgroup of patients with high c-MET expression (anticipated to be ~84% of patients, and/or high c-MET copy number (anticipated >10% and largely overlapping with MET IHC). V. Single agent activity for ARQ 197 (tivantinib) in patients who have failed cetuximab. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive cetuximab intravenously (IV) over 60-120 minutes on days 1 and 15 and tivantinib orally (PO) twice daily (BID) on days 1-28. ARM II: Patients receive cetuximab IV over 60-120 minutes on days 1 and 15. Patients who fail cetuximab as a single agent may receive single agent tivantinib PO BID on days 1-28. In both arms, courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 5 years.

OBJECTIVES: Primary - Determine whether the addition of cetuximab to postoperative intensity-modulated radiotherapy (IMRT) will improve overall survival (OS) in patients with locally advanced squamous cell carcinoma of the head and neck at intermediate risk following surgery. Secondary - Assess the impact of the addition of cetuximab to postoperative IMRT on disease-free survival (DFS) of these patients. - Assess the impact of the addition of cetuximab to postoperative IMRT on acute and late dysphagia, xerostomia, skin toxicity, and other toxicities according to common Toxicity Criteria for Adverse Effects (CTCAE), v. 4 and their relationships with patient-reported outcomes at 3, 12, and 24 months. - Analyze tumor for epidermal growth factor receptor (EGFR), specifically the extent of EGFR overexpression by immuno-histochemistry (IHC) and FISH analysis, EGFRvIII expression, as well as the association of these assay data with OS and DFS. - Analyze tumor for human papillomavirus (HPV) infection (as defined by in situ hybridization), specifically, within the cohort of patients with oropharynx cancer, to perform an exploratory analysis of the impact of HPV on DFS and OS of this patient subset. - Analyze tumor DNA for TP53 mutations as a predictor of response to cetuximab and prognosis. - Analyze germline DNA of polymorphic variants in EGFR intron repeats as a predictor of response to cetuximab. Tertiary - Assess the impact of the addition of cetuximab to postoperative IMRT on loco-regional control. - Assess the impact of the addition of cetuximab to postoperative IMRT on patient-reported quality of life, swallowing, xerostomia, and skin toxicity based on head and neck specific instruments, including the Performance Status Scale for Head and Neck Cancer (PSS-HN), the Functional Assessment of Cancer Therapy-Head & Neck (FACT-H&N), the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS), and the Dermatology Life Quality Index (DLQI). - Assess the impact of the addition of cetuximab to postoperative IMRT on cost-utility analysis using the EuroQol (EQ-5D). - Evaluate the utility of image-guided radiotherapy (IGRT) as a means of enhancing the efficacy (i.e., loco-regional control) of IMRT while reducing the acute and/or late toxicity (particularly xerostomia) and improving patient-reported outcomes (particularly XeQOLS scores). - Retrospectively compare the loco-regional control rate in patients treated with IMRT alone (no IGRT or cetuximab) with similar patients treated with external beam radiotherapy alone in the postoperative clinical trial Radiation Therapy Oncology Group (RTOG)-95 01. OUTLINE: This is a multicenter study. Patients are stratified according to clinical stage (T2-3 vs T4a), EGFR expression (high [≥ 80% of cells staining positive] vs low [< 80% of cells staining positive] vs not evaluable), primary site of disease (oral cavity vs larynx vs oropharynx p16+ vs oropharynx p16- vs oropharynx, p16 not evaluable), and use of image-guided radiotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms. - Arm I: Patients undergo intensity-modulated radiotherapy (IMRT) once daily 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity. - Arm II: Patients undergo IMRT as in arm I. Patients also receive cetuximab IV over 1-2 hours once weekly beginning at least 5 days prior to the start of IMRT and continuing for 4 weeks after the completion of IMRT (for a total of 11 doses) in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline and at 3, 12, and 24 months. Tissue samples are collected periodically for further laboratory analysis. After completion of study treatment, patients are followed up at 1 and 3 months, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

OBJECTIVES: Primary - Determine the negative predictive value of PET/CT imaging based upon pathologic sampling of the neck lymph nodes in patients with head and neck cancer planning to undergo N0 neck surgery. - Determine the potential of PET/CT imaging to change treatment. Secondary - Estimate the sensitivity and diagnostic yield of PET/CT imaging for detecting occult metastasis in the clinical N0 neck (both by neck and lymph node regions) or other local sites. - Determine the effect of other factors (e.g., tumor size, location, secondary primary tumors, or intensity of FDG uptake) that can lead to identification of subsets of patients that could potentially forego neck dissection or that can provide preliminary data for subsequent studies. - Compare the cost-effectiveness of using PET/CT imaging for staging head and neck cancer vs current good clinical practices. - Evaluate the incidence of occult distant body metastasis discovered by whole-body PET/CT imaging. - Correlate PET/CT imaging findings with CT/MRI findings and biomarker results. - Evaluate the quality of life of these patients, particularly of those patients whose management could have been altered by imaging results. - Evaluate PET/CT imaging and biomarker data for complementary contributions to metastatic disease prediction. - Compare baseline PET/CT imaging and biomarker data with 2-year follow up as an adjunct assessment of their prediction of recurrence, disease-free survival, and overall survival. - Determine the proportion of neck dissections that are extended (i.e., additional levels that clinicians intend to dissect beyond the initial surgery plan) based on local-reader PET/CT imaging findings shared with the surgeon before dissection. - Estimate the optimum cutoff value of standardized uptake values for diagnostic accuracy of PET/CT imaging. - Evaluate the impact of PET/CT imaging on the N0 neck across different tumor subsites (defined by anatomic location). OUTLINE: This is a multicenter study. Patients undergo fludeoxyglucose F 18-PET/CT imaging. Approximately 14 days later, patients undergo unilateral or bilateral neck dissection. Patients complete quality-of-life questionnaires at baseline and at 1, 12, and 24 months after surgery. Patients undergo blood and tissue sample collection periodically for biomarker analysis. Patients are followed up periodically for up to 2 years after surgery.

This study will determine whether patients who receive regular physical therapy immediately following a modified neck dissection surgery will report decreased shoulder disability, decreased pain, improved or maintained shoulder range of motion and strength, and improved quality of life than those who receive only home instruction.