Study of Radiation (RT) Concurrent With Cetuximab in Patients With Advanced Head and Neck Squamous Cell Carcinoma (SCC)

Phase 2

Terminated

Brief Summary: This is a single-arm, phase II trial to characterize the clinical outcome of standard of care, cetuximab concurrent with radiation, in a special population (head and neck cancer patients who cannot tolerate concurrent chemoradiotherapy due to advanced age, poor performance status or concurrent illness), and to determine if biomarker response to a loading dose of cetuximab is predictive of that outcome.

Detailed Description: Primary Objective 1: Determine changes in tumor EGFR, pEGFR, downstream signaling and novel phosphoproteins following a loading dose of cetuximab in patients who are poor candidates for chemoradiation (age =70 years or with significant co-morbidities) and are therefore treated with cetuximab with radiation.

Primary Objective 2: Characterize clinical outcomes, including local recurrence, progression-free survival and overall survival in these patients, and correlate these clinical outcomes with the changes in tumor EGFR, pEGFR, downstream signaling, and novel phosphoproteins.

Primary Objective 3: Describe the toxicity, in particular mucositis/dysphagia, of this regimen.

Secondary Objective 1: Conduct normal mucosa EGFR assessment for comparison with tumor sample.

Secondary Objective 2: Correlate HPV presence and titer with p53 status and clinical outcome.

Recruitment & Eligibility

Inclusion Criteria

Patients must have pathologically-confirmed, previously untreated, clinically accessible (without general anesthesia) locally advanced squamous cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, or nonresectable head and neck squamous cell carcinomas of the skin.
Patients will be limited to:
- ≥ 70 years of age, OR
- with co-morbidities that preclude treatment with standard platinum-based chemotherapy, as determined by the treating physician, OR
- KPS ≤ 80, OR
- Creatinine clearance < 30 cc/min
Laboratory criteria:
- WBC > 3500/ul
- Granulocyte > 1500/ul
- Platelet count > 100,000/ul
- Total Bilirubin < 1.5 X ULN
- AST and ALT < 2.5 X ULN
Patients must give documented informed consent to participate in this study.

Exclusion Criteria

Prior head and neck malignancy, or history of other prior non-head and neck malignancy within the past 3 years (excluding skin cancer and early stage treated prostate cancer).
Prior head and neck radiation or chemotherapy.
Documented evidence of distant metastases.
Patients with nasopharyngeal carcinoma.
Any medical or psychiatric illness, which, in the opinion of the principal investigator, would compromise the patient's ability to tolerate this treatment.
Patients with psychiatric/social situations that would limit compliance with study requirements are not eligible.
Patients with prior anti-epidermal growth-factor receptor antibody therapy (antibody or small molecule).
Patients residing in prison.

Arm && Interventions

Group	Intervention	Description
Treatment	50-60 Gy and 70 Gy	-
Treatment	Cetuximab	-

Primary Outcome Measures

Name	Time	Method
Mean Change in Tumor Epidermal Growth Factor Receptor (EGFR)	At baseline (pre-loading dose) and day 7 post-loading dose	The ratio (fold change) of tumor EGFR post-loading dose/pre-loading dose of cetuximab. Reported as the mean of fold changes across all participants who had an evaluable tumor sample.
Mean Change in Tumor Phosphorylated EGFR (pEGFR)	At baseline (pre-loading dose) and day 7 post-loading dose	The ratio (fold change) of tumor pEGFR post-loading dose/pre-loading dose of cetuximab. Reported as the mean of fold changes across all participants who had an evaluable tumor sample.
Progression Free Survival Rate	At 1 and 2 years	Percentage of participants who survived without recurrent disease, from the time of enrollment to 1 and 2 years.
Overall Survival Rate	At 1 and 2 Years	Percentage of participants alive at 1 and 2 years after enrollment.
Number of Participants With Treatment Related Toxicities	3 years	Toxicities are measured by number of participants who experience one or more types or indicator of toxicity, shown as all grades and grades 3-4. As each participant could have multiple toxicities, the total number of incidents outnumbers the number of participants. Toxicities are graded according to the CTCAE v4.

Secondary Outcome Measures

Name	Time	Method
Change in Tumor EGFR Level Relative to EGFR in Normal Mucosa	At baseline (pre-loading dose) and day 7 post-loading dose	Normal mucosa EGFR was assessed for comparison with EGFR in tumor sample. The fold change in tumor EGFR level at post-loading dose/pre-loading dose of cetuximab, relative to fold change in normal mucosa EGFR level post-loading dose/pre-loading dose of cetuximab was summarized across all participants who had an evaluable tumor sample and normal mucosa sample. The value reported is the ratio of fold change in tumor/fold change in buccal EGFR.
Change in Tumor pEGFR Level Relative to pEGFR in Normal Mucosa	At baseline (pre-loading dose) and day 7 post-loading dose	Normal mucosa pEGFR was assessed for comparison with pEGFR in tumor sample. The fold change in tumor pEGFR level post-loading dose/pre loading dose of cetuximab, relative to fold change in normal mucosa pEGFR level post-loading dose/pre-loading dose of cetuximab was summarized across all participants who had an evaluable tumor sample and normal mucosa sample. The value reported is the ratio of fold change in tumor/fold change in buccal pEGFR.

Locations (2): University of Michigan Medical Center
🇺🇸
Ann Arbor, Michigan, United States
University of Michigan Veterans Administration Hospital
🇺🇸
Ann Arbor, Michigan, United States