Radiation Therapy With Durvalumab or Cetuximab in Treating Patients With Locoregionally Advanced Head and Neck Cancer Who Cannot Take Cisplatin

Completed · Phase 2/Phase 3

Conditions studied: Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Head and Neck Squamous Cell Carcinoma, Hypopharyngeal Squamous Cell Carcinoma, Laryngeal Squamous Cell Carcinoma, Oral Cavity Squamous Cell Carcinoma, Oropharyngeal Squamous Cell Carcinoma, Pathologic Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Squamous Cell Carcinoma of Unknown Primary, Stage III Hypopharyngeal Carcinoma AJCC v8, Stage III Laryngeal Cancer AJCC v8, Stage III Lip and Oral Cavity Cancer AJCC v8, Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8, Stage IVA Hypopharyngeal Carcinoma AJCC v8, Stage IVA Laryngeal Cancer AJCC v8, Stage IVA Lip and Oral Cavity Cancer AJCC v8, Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8, Stage IVB Hypopharyngeal Carcinoma AJCC v8, Stage IVB Laryngeal Cancer AJCC v8, Stage IVB Lip and Oral Cavity Cancer AJCC v8, Stage IVB Oropharyngeal (p16-Negative) Carcinoma AJCC v8

In brief

This phase II/III trial studies how well radiation therapy works with durvalumab or cetuximab in treating patients with head and neck cancer that has spread to a local and/or regional area of the body who cannot take cisplatin. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cetuximab is a monoclonal antibody that 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 facts

Study ID

NCT03258554

Run by

National Cancer Institute (NCI)

People needed

196

Starts

2018-04-03

Expected to finish

2025-09-04

Last updated by the study team

2026-08-03

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• PRIOR TO STEP 1 REGISTRATION INCLUSION CRITERIA
• 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 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 (with the required block for PD-L1) 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; however, if a cell block derived from the FNA is available, it is allowable if there are sufficient cells present in the block for PD-L1 testing; Dr. Jordan will determine this upon receipt; for sites submitting FNA cell blocks for ALL patients they must do so within 7-10 business days from registering the patient; sites must confirm with their cytology/pathology labs to make sure they can provide the required material as the bank must be able to retain these samples for the mandatory testing
• Patients must have locoregionally advanced head and neck squamous cell carcinoma (HNSCC)
• For p16-positive oropharyngeal/unknown primaries, American Joint Committee on Cancer [AJCC] 8th edition stage III and selected stage I-II based on smoking status in pack-years
• For laryngeal, hypopharyngeal, and oral cavity primaries and p16-negative oropharyngeal/unknown primaries, AJCC 8th edition stage III-IVB
• Based on the following minimum diagnostic workup within 60 days prior to step 1 registration:
• General history and physical examination by a radiation oncologist or medical oncologist 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; note that the CT portion of the PET/CT must be of diagnostic quality, including contrast administration unless contraindicated. If the CT portion of the PET/CT study is low-dose (non-diagnostic), then an additional CT or MRI study with contrast (unless contraindicated) is required
• 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)
• Age >= 70 with moderate to severe comorbidity or vulnerability to cisplatin, defined as having one or more of the following conditions within 30 days prior to step 1 registration:
• Modified Charlson Comorbidity Index >= 1
• Adult Comorbidity Evaluation (ACE)-27 Index >= 1
• Generalized Competing Event Model for Cancer Risk (GCE) omega PFS score < 0.80
• Geriatric screening (G-8) score =< 14
• Cancer and Aging Research Group (CARG) toxicity score >= 30%
• Cumulative Illness Rating scale for Geriatrics (CIRS-G) score >= 4 OR
• Age < 70 with severe comorbidity or vulnerability to cisplatin, defined as having two or more of the following conditions within 30 days prior to step 1 registration
• Modified Charlson Comorbidity Index >= 1
• ACE-27 Index >= 1
• GCE omega PFS-score < 0.80
• G-8 score =< 14
• CARG Toxicity score >= 30%

You may not qualify if…

• PRIOR TO STEP 1 REGISTRATION EXCLUSION CRITERIA
• Prior invasive malignancy within the past 3 years (except for non-melanomatous skin cancer, and early stage treated prostate cancer); synchronous head and neck primaries are ineligible
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• Note: Prior external beam radiotherapy is excluded, but iodine 131 is allowed
• Prior immunotherapy
• Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy, or immune therapy for the study cancer
• Major surgery within 28 days prior to step 1 registration
• Proven evidence of distant metastases
• If both of the following conditions are present, the patient is ineligible:
• =< 10 pack-year smoking history
• p16-positive carcinoma of the oropharynx or unknown primary that are T0-3, N0-1 (AJCC 8th Edition)
• Note: in the event that a registered patient with =< 10 pack-years has a p16-positive result on central review with the tumor and nodal stage T0-3, N0-1 (AJCC 8th Edition), then the site will be notified that the patient is ineligible
• Zubrod performance status >= 3
• Body weight =< 30 kg
• Patients with oral cavity cancer are excluded from participation if the patient is medically operable and resection of the primary tumor is considered technically feasible by an oral or head and neck cancers surgical subspecialist;(please consult the surgical oncology co-principal investigator [PI], Steven Chang, Doctor of Medicine [MD], if clarification is needed on an individual case)
• Sodium < 130 mmol/L or > 155 mmol/L (within 14 days of step 1 registration, unless corrected prior to step 1 registration)
• Potassium < 3.5 mmol/L or > 6 mmol/L (within 14 days of step 1 registration, unless corrected prior to step 1 registration)
• Fasting glucose < 40 mg/dl or > 400 mg/dl (within 14 days of step 1 registration, unless corrected prior to step 1 registration)
• Serum calcium (ionized or adjusted for albumin) < 7 mg/dl or > 12.5 mg/dl (within 14 days of step 1 registration, unless corrected prior to step 1 registration)
• Magnesium < 0.9 mg/dl or > 3 mg/dl (within 14 days of step 1 registration, unless corrected prior to step 1 registration)
• Unstable angina and/or congestive heart failure requiring hospitalization within 3 months prior to step 1 registration
• Transmural myocardial infarction within 3 months prior to step 1 registration
• Respiratory illness requiring hospitalization at the time of step 1 registration
• Note: if the respiratory illness is resolved and the patient meets the eligibility status above, then the patient can be considered for the trial
• Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to require oxygen therapy within 1 year prior to step 1 registration

Where it is running

• University of South Alabama Mitchell Cancer Institute — Mobile, Alabama, United States
• Banner MD Anderson Cancer Center — Gilbert, Arizona, United States
• CTCA at Western Regional Medical Center — Goodyear, Arizona, United States
• Banner University Medical Center - Tucson — Tucson, Arizona, United States
• University of Arizona Cancer Center-North Campus — Tucson, Arizona, United States
• Kaiser Permanente-Deer Valley Medical Center — Antioch, California, United States
• Sutter Cancer Centers Radiation Oncology Services-Auburn — Auburn, California, United States
• Alta Bates Summit Medical Center-Herrick Campus — Berkeley, California, United States
• City of Hope Comprehensive Cancer Center — Duarte, California, United States
• Kaiser Permanente Dublin — Dublin, California, United States
• Kaiser Permanente-Fremont — Fremont, California, United States
• Fresno Cancer Center — Fresno, California, United States
• Kaiser Permanente-Fresno — Fresno, California, United States
• UC San Diego Moores Cancer Center — La Jolla, California, United States
• Cedars Sinai Medical Center — Los Angeles, California, United States
• Kaiser Permanente-Modesto — Modesto, California, United States
• Kaiser Permanente Oakland-Broadway — Oakland, California, United States
• Kaiser Permanente-Oakland — Oakland, California, United States
• Stanford Cancer Institute Palo Alto — Palo Alto, California, United States
• VA Palo Alto Health Care System — Palo Alto, California, United States
• Kaiser Permanente-Rancho Cordova Cancer Center — Rancho Cordova, California, United States
• Kaiser Permanente-Richmond — Richmond, California, United States
• Rohnert Park Cancer Center — Rohnert Park, California, United States
• Kaiser Permanente-Roseville — Roseville, California, United States
• University of Alabama at Birmingham Cancer Center — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.