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
About this trial
This is an interventional treatment trial for Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
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 < 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%
- 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 < 60 cc/min; for this calculation, use the Cockcroft-Gault formula
- Zubrod performance status 2 prior to step 1 registration
- Pre-existing peripheral neuropathy grade >= 1
History of hearing loss, defined as either:
- Existing need of a hearing aid OR
- >= 25 decibel shift over 2 contiguous frequencies on a pretreatment hearing test as clinically indicated
- Absolute neutrophil count (ANC) >= 1,000 cells/mm^3 (within 14 days prior to step 1 registration)
- Platelets >= 100,000 cells/mm^3 (within 14 days prior to step 1 registration)
- Hemoglobin >= 9.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 9.0 g/dl is acceptable) (within 14 days prior to step 1 registration)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 times institutional upper limit of normal (within 14 days prior to step 1 registration)
- Serum bilirubin =< 1.5 x institutional upper limit of normal (within 14 days prior to step 1 registration)
- Measured creatinine clearance (CL) > 30 mL/min or calculated creatinine CL > 30 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance (within 14 days prior to step 1 registration)
For women of childbearing potential, a negative serum or urine pregnancy test within 14 days prior to step 1 registration; Note: women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply:
- Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
- Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
- The patient or a legally authorized representative must provide study-specific informed consent prior to step 1 registration
- PRIOR TO STEP 2 REGISTRATION INCLUSION CRITERIA
For patients with oropharyngeal or unknown primaries: p16 determination by immunohistochemistry (defined as greater than 70% strong nuclear or nuclear and cytoplasmic staining of tumor cells), confirmed by central pathology review
- Note: for patients with oral cavity, laryngeal, and hypopharyngeal primaries, analysis of p16 status prior to step 2 registration/randomization is not required (p16 status will be analyzed centrally post-hoc); step 2 registration for these patients can be completed after step 1 registration
Exclusion Criteria:
- 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
- History of (non-infectious) pneumonitis that required steroids or current pneumonitis
- Clinically apparent jaundice and/or known coagulation defects
Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.)
The following are exceptions to this criterion:
- Patients with vitiligo or alopecia;
- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement;
- Any chronic skin condition that does not require systemic therapy;
- Patients without active disease in the last 5 years may be included but only after consultation with the medical oncology study chair;
- Patients with celiac disease controlled by diet alone
- History of active primary immunodeficiency including, but not limited to acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; Note: human immunodeficiency virus (HIV) testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatment involved in this protocol may be immunosuppressive; patients with known HIV, CD4 counts >= 200/uL, and undetectable viral loads who are stable on an antiretroviral regimen may be included
- Current or prior use of immunosuppressive medication within 14 days before step 1 registration, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
- Receipt of live attenuated vaccination within 30 days prior to step 1 registration
- Medical or psychiatric illness which would compromise the patient's ability to tolerate treatment or limit compliance with study requirements
- Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception during treatment and for 6 months after the last dose of cetuximab or MEDI14736 (durvalumab); this exclusion is necessary because the treatment involved in this study may be significantly teratogenic; women who are breastfeeding are also excluded
- Prior allergic reaction or hypersensitivity to cetuximab or MEDI4736 (durvalumab) or any of study drug excipients
- History of allogenic organ transplantation
- Uncontrolled hypertension
- Uncontrolled cardiac arrhythmia
- Uncontrolled serious chronic gastrointestinal condition associated with diarrhea
- Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice), hepatitis B (known positive hepatitis B virus [HBV] surface antigen [HBsAg] result), hepatitis C; patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible; patients positive for hepatitis C (hepatitis C virus [HCV]) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
Sites / Locations
- University of Alabama at Birmingham Cancer Center
- University of South Alabama Mitchell Cancer Institute
- Banner MD Anderson Cancer Center
- CTCA at Western Regional Medical Center
- Banner University Medical Center - Tucson
- University of Arizona Cancer Center-North Campus
- Kaiser Permanente-Deer Valley Medical Center
- Sutter Cancer Centers Radiation Oncology Services-Auburn
- Alta Bates Summit Medical Center-Herrick Campus
- City of Hope Comprehensive Cancer Center
- Kaiser Permanente Dublin
- Kaiser Permanente-Fremont
- Fresno Cancer Center
- Kaiser Permanente-Fresno
- UC San Diego Moores Cancer Center
- Cedars Sinai Medical Center
- Kaiser Permanente-Modesto
- Kaiser Permanente Oakland-Broadway
- Kaiser Permanente-Oakland
- Stanford Cancer Institute Palo Alto
- VA Palo Alto Health Care System
- Kaiser Permanente-Rancho Cordova Cancer Center
- Kaiser Permanente-Richmond
- Rohnert Park Cancer Center
- Kaiser Permanente-Roseville
- Sutter Cancer Centers Radiation Oncology Services-Roseville
- The Permanente Medical Group-Roseville Radiation Oncology
- Kaiser Permanente Downtown Commons
- Sutter Medical Center Sacramento
- University of California Davis Comprehensive Cancer Center
- Kaiser Permanente-South Sacramento
- South Sacramento Cancer Center
- Kaiser Permanente-San Francisco
- UCSF Medical Center-Mount Zion
- UCSF Medical Center-Mission Bay
- Kaiser Permanente-Santa Teresa-San Jose
- Kaiser Permanente San Leandro
- Kaiser San Rafael-Gallinas
- Kaiser Permanente Medical Center - Santa Clara
- Kaiser Permanente-Santa Rosa
- City of Hope South Pasadena
- Kaiser Permanente Cancer Treatment Center
- Kaiser Permanente-South San Francisco
- Kaiser Permanente-Stockton
- Torrance Memorial Physician Network - Cancer Care
- Torrance Memorial Medical Center
- Gene Upshaw Memorial Tahoe Forest Cancer Center
- Kaiser Permanente Medical Center-Vacaville
- Kaiser Permanente-Vallejo
- Kaiser Permanente-Walnut Creek
- University of Colorado Hospital
- Penrose-Saint Francis Healthcare
- UCHealth Memorial Hospital Central
- Memorial Hospital North
- Poudre Valley Hospital
- McKee Medical Center
- Smilow Cancer Hospital-Hamden Care Center
- Yale University
- Smilow Cancer Hospital Care Center-Trumbull
- Smilow Cancer Hospital Care Center - Waterford
- Beebe South Coastal Health Campus
- Helen F Graham Cancer Center
- Beebe Health Campus
- UM Sylvester Comprehensive Cancer Center at Coral Gables
- UM Sylvester Comprehensive Cancer Center at Deerfield Beach
- Baptist MD Anderson Cancer Center
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- Moffitt Cancer Center
- Grady Health System
- Emory University Hospital Midtown
- Emory University Hospital/Winship Cancer Institute
- Augusta University Medical Center
- Hawaii Cancer Care Inc - Waterfront Plaza
- Queen's Medical Center
- The Cancer Center of Hawaii-Liliha
- Saint Alphonsus Cancer Care Center-Caldwell
- Saint Alphonsus Cancer Care Center-Nampa
- Northwestern University
- John H Stroger Jr Hospital of Cook County
- Rush University Medical Center
- University of Illinois
- Decatur Memorial Hospital
- Crossroads Cancer Center
- Western Illinois Cancer Treatment Center
- Methodist Medical Center of Illinois
- OSF Saint Francis Medical Center
- Memorial Medical Center
- Carle Cancer Center
- IU Health North Hospital
- Parkview Hospital Randallia
- Parkview Regional Medical Center
- Indiana University/Melvin and Bren Simon Cancer Center
- Sidney and Lois Eskenazi Hospital
- Community Cancer Center East
- Community Cancer Center South
- Community Cancer Center North
- Mercy Cancer Center-West Lakes
- Iowa Methodist Medical Center
- Mercy Medical Center - Des Moines
- University of Kansas Cancer Center
- University of Kansas Cancer Center-Overland Park
- Salina Regional Health Center
- University of Kansas Hospital-Westwood Cancer Center
- Ascension Via Christi Hospitals Wichita
- University of Kentucky/Markey Cancer Center
- Norton Hospital Pavilion and Medical Campus
- The James Graham Brown Cancer Center at University of Louisville
- Norton Brownsboro Hospital and Medical Campus
- East Jefferson General Hospital
- Greater Baltimore Medical Center
- Boston Medical Center
- Lahey Hospital and Medical Center
- Saint Joseph Mercy Hospital
- University of Michigan Comprehensive Cancer Center
- McLaren Cancer Institute-Bay City
- Saint Joseph Mercy Brighton
- Henry Ford Cancer Institute-Downriver
- Saint Joseph Mercy Canton
- Saint Joseph Mercy Chelsea
- McLaren Cancer Institute-Clarkston
- Henry Ford Macomb Hospital-Clinton Township
- Wayne State University/Karmanos Cancer Institute
- Henry Ford Hospital
- Weisberg Cancer Treatment Center
- McLaren Cancer Institute-Flint
- Singh and Arora Hematology Oncology PC
- Allegiance Health
- Karmanos Cancer Institute at McLaren Greater Lansing
- Mid-Michigan Physicians-Lansing
- Sparrow Hospital
- McLaren Cancer Institute-Lapeer Region
- McLaren Cancer Institute-Macomb
- McLaren Cancer Institute-Northern Michigan
- McLaren-Port Huron
- Ascension Saint Mary's Hospital
- Henry Ford West Bloomfield Hospital
- Sanford Joe Lueken Cancer Center
- Fairview Ridges Hospital
- Miller-Dwan Hospital
- Fairview Southdale Hospital
- Unity Hospital
- Hennepin County Medical Center
- Mayo Clinic in Rochester
- Coborn Cancer Center at Saint Cloud Hospital
- Regions Hospital
- Saint Francis Medical Center
- Siteman Cancer Center at West County Hospital
- Washington University School of Medicine
- Mercy Hospital Saint Louis
- Siteman Cancer Center at Saint Peters Hospital
- Billings Clinic Cancer Center
- Kalispell Regional Medical Center
- CHI Health Saint Francis
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
- Memorial Sloan Kettering Basking Ridge
- Hackensack University Medical Center
- Memorial Sloan Kettering Monmouth
- Memorial Sloan Kettering Bergen
- University of New Mexico Cancer Center
- New Mexico Oncology Hematology Consultants
- Montefiore Medical Center - Moses Campus
- James J Peters VA Medical Center
- Roswell Park Cancer Institute
- Memorial Sloan Kettering Commack
- Memorial Sloan Kettering Westchester
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
- Memorial Sloan Kettering Cancer Center
- University of Rochester
- Stony Brook University Medical Center
- State University of New York Upstate Medical University
- Memorial Sloan Kettering Nassau
- Atrium Health Stanly/LCI-Albemarle
- UNC Lineberger Comprehensive Cancer Center
- Carolinas Medical Center/Levine Cancer Institute
- Atrium Health Pineville/LCI-Pineville
- Atrium Health Cabarrus/LCI-Concord
- Margaret R Pardee Memorial Hospital
- Atrium Health Union/LCI-Union
- Sanford Roger Maris Cancer Center
- Cleveland Clinic Mercy Hospital
- Aultman Health Foundation
- Geauga Hospital
- University of Cincinnati Cancer Center-UC Medical Center
- Case Western Reserve University
- MetroHealth Medical Center
- Cleveland Clinic Foundation
- Ohio State University Comprehensive Cancer Center
- Cleveland Clinic Cancer Center Mansfield
- UH Seidman Cancer Center at Lake Health Mentor Campus
- North Coast Cancer Care
- ProMedica Flower Hospital
- University of Cincinnati Cancer Center-West Chester
- UHHS-Westlake Medical Center
- Cleveland Clinic Wooster Family Health and Surgery Center
- University of Oklahoma Health Sciences Center
- Good Samaritan Hospital
- Providence Portland Medical Center
- Providence Saint Vincent Medical Center
- Kaiser Permanente Northwest
- Jefferson Abington Hospital
- Crozer-Keystone Regional Cancer Center at Broomall
- Christiana Care Health System-Concord Health Center
- Geisinger Medical Center
- Penn State Milton S Hershey Medical Center
- Geisinger Medical Oncology-Lewisburg
- Lewistown Hospital
- Forbes Hospital
- Fox Chase Cancer Center
- Temple University Hospital
- Allegheny General Hospital
- UPMC-Shadyside Hospital
- Guthrie Medical Group PC-Robert Packer Hospital
- Reading Hospital
- Wexford Health and Wellness Pavilion
- Geisinger Wyoming Valley/Henry Cancer Center
- Asplundh Cancer Pavilion
- Medical University of South Carolina
- Gibbs Cancer Center-Pelham
- Rock Hill Radiation Therapy Center
- Spartanburg Medical Center
- Avera Cancer Institute
- Sanford USD Medical Center - Sioux Falls
- M D Anderson Cancer Center
- Norris Cotton Cancer Center-North
- University of Virginia Cancer Center
- Sentara Norfolk General Hospital
- VCU Massey Cancer Center at Stony Point
- Virginia Commonwealth University/Massey Cancer Center
- University of Washington Medical Center - Montlake
- West Virginia University Healthcare
- Langlade Hospital and Cancer Center
- Saint Vincent Hospital Cancer Center Green Bay
- Saint Vincent Hospital Cancer Center at Saint Mary's
- Aurora BayCare Medical Center
- UW Cancer Center Johnson Creek
- Aurora Cancer Care-Kenosha South
- Gundersen Lutheran Medical Center
- University of Wisconsin Carbone Cancer Center
- Aurora Bay Area Medical Group-Marinette
- Froedtert Menomonee Falls Hospital
- Aurora Saint Luke's Medical Center
- Medical College of Wisconsin
- Zablocki Veterans Administration Medical Center
- ProHealth D N Greenwald Center
- ProHealth Oconomowoc Memorial Hospital
- Vince Lombardi Cancer Clinic-Sheboygan
- Aurora Medical Center in Summit
- UW Cancer Center at ProHealth Care
- Aspirus Regional Cancer Center
- Aurora West Allis Medical Center
- Froedtert West Bend Hospital/Kraemer Cancer Center
- London Regional Cancer Program
- University Health Network-Princess Margaret Hospital
- The Research Institute of the McGill University Health Centre (MUHC)
- Allan Blair Cancer Centre
Arms of the Study
Arm 1
Arm 2
Arm 3
Active Comparator
Experimental
Experimental
RT + Cetuximab
RT + Durvalumab
(Lead-in) RT + Durvalumab
Intensity-modulated radiation therapy (IMRT) for seven weeks, 5 fractions/week. Cetuximab 400 mg/m^2 IV starts one week prior to RT, then 250 mg/m^2 weekly for seven additional cycles in the absence of disease progression or unacceptable toxicity.
IMRT for seven weeks, 5 fractions/week. Durvalumab 1500 mg IV starts two weeks prior to RT and continues every 4 weeks for a total of seven cycles in the absence of disease progression or unacceptable toxicity.
IMRT for seven weeks, 5 fractions/week. Durvalumab 1500 mg IV starts two weeks prior to RT and continues every 4 weeks for a total of seven cycles in the absence of disease progression or unacceptable toxicity.