Phase 3
N=10
Radiation Therapy With Durvalumab or Cetuximab in Treating Patients With Locoregionally Advanced Head and Neck Cancer Who Cannot Take Cisplatin
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
Bottom Line
View on ClinicalTrials.gov: NCT03258554 ↗Enrolled (actual)
10
Serious AEs
73.2%
Results posted
Oct 2023
Primary outcome: Primary: Number of Participants With Dose-limiting Toxicity (DLT) [Lead-in Phase] — 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Cetuximab (Biological); Durvalumab (Biological); Intensity-Modulated Radiation Therapy (Radiation); Laboratory Biomarker Analysis (Other); Quality-of-Life Assessment (Other); Questionnaire Administration (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Sep 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose-limiting Toxicity (DLT) [Lead-in Phase] |
— | — |
| PRIMARY Progression-free Survival (Percentage of Participants Alive Without Progression) [Phase II Primary] |
63.7; 50.6 | 0.8878 |
| PRIMARY Overall Survival (Percentage of Participants Alive) [Originally Phase III Primary / Now Phase II Secondary] |
77.5; 69.3 | 0.8175 |
| SECONDARY Locoregional Failure (Percentage of Participants With Locoregional Failure) |
18.9; 31.3 | 0.1001 |
| SECONDARY Distant Metastasis (Percentage of Participants With Distant Metastasis) |
12.1; 9.5 | 0.5197 |
| SECONDARY Competing Mortality (Percentage of Participants Who Died Due to Causes Other Than Study Cancer) |
5.3; 10.5 | 0.3201 |
| SECONDARY Percentage of Participants With Complete or Partial Response at 4-month Scan Determined by Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 |
72.7; 75.9 | 1.00 |
| SECONDARY Number of Participants by Highest Grade Adverse Event Reported |
12; 36; 37; 57; 11; 15 | 0.0688 |
| SECONDARY Change in Quality of Life (QOL) Analysis |
— | — |
| SECONDARY Change in Swallowing QOL Using Total Composite M. D. Anderson Dysphagia Inventory (MDADI) Score |
— | — |
| SECONDARY Progression-free Survival (Percentage of Participants Alive Without Progression) by Baseline PD-L1 (Programmed Cell Death Ligand 1) Expression |
59.9; 54.8; 61.5; 30.0 | 0.41 |
| SECONDARY Progression-free Survival (Percentage of Participants Alive Without Progression) by Baseline p16 Status |
74.8; 68.8; 48.1; 23.2 | 0.61 |
Summary
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.
Eligibility Criteria
Inclusion Criteria
- 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 = 30%
- Cumulative Illness Rating scale for Geriatrics (CIRS-G) score >= 4 OR
- Age = 1
- ACE-27 Index >= 1
- GCE omega PFS-score = 30%
- CIRS-G score >= 4 OR
- Age >= 18 with an absolute or relative contraindication to cisplatin, defined as one or more of the following within 30 days prior to step 1 registration:
- Creatinine clearance (CC) > 30 and
Data sourced from ClinicalTrials.gov (NCT03258554). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.