Randomized Phase II/III Trial of Radiotherapy with Concurrent MEDI4736 (Durvalumab) Vs. Radiotherapy with Concurrent Cetuximab in Patients with Stage III-IVB Head and Neck Cancer with a Contraindication to Cisplatin

This randomized phase II/III trial studies how well radiation therapy works with durvalumab or cetuximab in treating patients with stage III-IVB head and neck cancer who cannot take cisplatin. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Monoclonal antibodies, such as durvalumab and cetuximab, may interfere with the ability of tumor cells to grow and spread. It is not known if radiation therapy with durvalumab will work better than the usual therapy of radiation therapy with cetuximab in treating patients with head and neck cancer.

Key Eligibility

•Patients must have pathologically confirmed, previously untreated, unresected squamous cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, or carcinoma of unknown head/neck primary within 60 days prior to step 1 registration; submission of hematoxylin and eosin (H&E) stained slides and formalin-fixed and paraffin-embedded (FFPE) tissue block (or punch biopsy of FFPE block) to the biospecimen bank at University of California, San Francisco (UCSF) for central review for oropharyngeal and unknown primaries and for p16 analysis for all other non- oropharyngeal primaries is mandatory for all patients; investigators should check with their pathology department regarding release of biospecimens before approaching patients about participation in the trial; for oropharyngeal and unknown primaries, submission of H&E and p16 stained slides to the biospecimen bank at UCSF for central review is also required prior to step 2 registration
◦Note: fine needle aspirates (FNA) samples are not acceptable since they do not provide enough material for PD-L1 and p16 testing

•Patients must have stage III-IVB head and neck squamous cell carcinoma (HNSCC) (American Joint Committee on Cancer [AJCC] seventh [7th] edition) based on the following minimum diagnostic workup within 60 days prior to step 1 registration:
◦General history and physical examination by a radiation oncologist, medical oncologist, and/or ear, nose and throat (ENT) or head & neck surgeon
◦For larynx, hypopharynx, and base of tongue primaries, a laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) is required, unless the patient cannot tolerate or refuses
◦Imaging of the head and neck with a neck CT or magnetic resonance imaging (MRI) (with contrast, unless contraindicated) or PET/CT (with contrast, unless contraindicated)
◦Chest imaging: chest CT with and without contrast (unless contraindicated) or PET/CT

•Patients must have a contraindication to cisplatin as defined in the following bullet points; sites must complete the online tool at comogram.org prior to step 1 registration to determine if the patient is eligible; the scores must be recorded on a case report form (CRF)
Phase II
Oral, Head and Neck
Benjamin Bridges , M.D.
NRG (NRG Oncology)
George Morris

The Pacific Cancer Research Consortium clinical trials are offered at multiple locations throughout Oregon, Washington, Alaska, California, and Idaho. To find a location near you, please contact the Patient Engagement Center at 844-552-2734.