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

Status: Active

Description

This randomized 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 or cetuximab, may help the body’s immune system attack the cancer, and 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
  • 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
  • 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)

Locations & Contacts

Alabama

Birmingham
University of Alabama at Birmingham Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 205-934-0220
Email: tmyrick@uab.edu
Mobile
University of South Alabama Mitchell Cancer Institute
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 251-445-9870
Email: pfrancisco@usouthal.edu

Arizona

Tucson
Banner University Medical Center - Tucson
Status: Active
Contact: Site Public Contact
Email: aselegue@email.arizona.edu
University of Arizona Cancer Center-North Campus
Status: Active
Contact: Site Public Contact
Phone: 800-327-2873

California

Antioch
Kaiser Permanente-Deer Valley Medical Center
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Auburn
Sutter Cancer Centers Radiation Oncology Services-Auburn
Status: Active
Contact: Site Public Contact
Phone: 415-209-2686
Email: bernicl@sutterhealth.org
Duarte
City of Hope Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-826-4673
Email: becomingapatient@coh.org
Fremont
Kaiser Permanente-Fremont
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Fresno
Fresno Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Kaiser Permanente-Fresno
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
La Jolla
UC San Diego Moores Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 858-822-5354
Email: cancercto@ucsd.edu
Modesto
Kaiser Permanente-Modesto
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Oakland
Kaiser Permanente Oakland-Broadway
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Kaiser Permanente-Oakland
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Palo Alto
Stanford Cancer Institute Palo Alto
Status: Active
Contact: Site Public Contact
Phone: 650-498-7061
Email: ccto-office@stanford.edu
Rancho Cordova
Kaiser Permanente-Rancho Cordova Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Richmond
Kaiser Permanente-Richmond
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Rohnert Park
Rohnert Park Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Roseville
Kaiser Permanente-Roseville
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
The Permanente Medical Group-Roseville Radiation Oncology
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Sacramento
Kaiser Permanente-South Sacramento
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
South Sacramento Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Sutter Medical Center Sacramento
Status: Active
Contact: Site Public Contact
Phone: 415-209-2686
Email: bernicl@sutterhealth.org
San Francisco
Kaiser Permanente-San Francisco
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
UCSF Medical Center-Mission Bay
Status: Active
Contact: Site Public Contact
Phone: 877-827-3222
UCSF Medical Center-Mount Zion
Status: Active
Contact: Site Public Contact
Phone: 877-827-3222
San Jose
Kaiser Permanente-Santa Teresa-San Jose
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
San Leandro
Kaiser Permanente San Leandro
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
San Rafael
Kaiser San Rafael-Gallinas
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Santa Clara
Kaiser Permanente Medical Center - Santa Clara
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Santa Rosa
Kaiser Permanente-Santa Rosa
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
South San Francisco
Kaiser Permanente Cancer Treatment Center
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Kaiser Permanente-South San Francisco
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Stockton
Kaiser Permanente-Stockton
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Truckee
Gene Upshaw Memorial Tahoe Forest Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 530-582-6450
Vacaville
Kaiser Permanente Medical Center-Vacaville
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Vallejo
Kaiser Permanente-Vallejo
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Walnut Creek
Kaiser Permanente-Walnut Creek
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org

Colorado

Aurora
University of Colorado Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 720-848-0650
Colorado Springs
Memorial Hospital North
Status: Active
Contact: Site Public Contact
Phone: 719-364-6700
Penrose-Saint Francis Healthcare
Status: Active
Contact: Site Public Contact
Phone: 308-398-6518
Email: clinicaltrials@sfmc-gi.org
UCHealth Memorial Hospital Central
Status: Active
Contact: Site Public Contact
Phone: 719-365-2406
Fort Collins
Poudre Valley Hospital
Status: Active
Contact: Site Public Contact
Phone: 970-297-6150
Loveland
McKee Medical Center
Status: Active
Contact: Site Public Contact
Phone: 303-777-2663
Email: ccrp@co-cancerresearch.org

Connecticut

New Haven
Yale University
Status: Active
Contact: Site Public Contact
Phone: 203-785-5702
Email: canceranswers@yale.edu
Waterford
Lawrence and Memorial Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 203-785-5702
Email: canceranswers@yale.edu

Delaware

Newark
Helen F Graham Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 302-623-4450
Email: KDempsey@christianacare.org

Florida

Coral Gables
UM Sylvester Comprehensive Cancer Center at Coral Gables
Status: Active
Contact: Site Public Contact
Phone: 305-243-2647
Deerfield Beach
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Status: Active
Contact: Site Public Contact
Phone: 305-243-2647
Jacksonville
Baptist MD Anderson Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 904-202-7468
Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 305-243-2647
Tampa
Moffitt Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-679-0775
Email: canceranswers@moffitt.org

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 404-778-1868
Emory University Hospital Midtown
Status: Active
Contact: Site Public Contact
Phone: 888-946-7447
Augusta
Augusta University Medical Center
Status: Active
Contact: Site Public Contact
Phone: 706-721-2388
Email: ga_cares@augusta.edu

Hawaii

Honolulu
Hawaii Cancer Care Inc-POB II
Status: Active
Contact: Site Public Contact
Phone: 808-524-6115
Queen's Medical Center
Status: Active
Contact: Site Public Contact
Phone: 808-545-8548
The Cancer Center of Hawaii-Liliha
Status: Active
Contact: Site Public Contact
Phone: 808-547-6881

Illinois

Chicago
John H Stroger Jr Hospital of Cook County
Status: Active
Contact: Site Public Contact
Phone: 312-864-5204
Northwestern University
Status: Active
Contact: Site Public Contact
Phone: 312-695-1301
Email: cancer@northwestern.edu
Rush University Medical Center
Status: Active
Contact: Site Public Contact
Phone: 312-942-5498
Email: clinical_trials@rush.edu
Decatur
Decatur Memorial Hospital
Status: Active
Contact: Site Public Contact
Phone: 217-876-4740
Email: rhamrick@dmhhs.org
Effingham
Crossroads Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 217-876-4740
Email: rhamrick@dmhhs.org
Peoria
Methodist Medical Center of Illinois
Status: Active
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com
OSF Saint Francis Medical Center
Status: Active
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com
Springfield
Memorial Medical Center
Status: Active
Contact: Site Public Contact
Phone: 217-788-3528
Urbana
Carle Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-446-5532
Email: Research@carle.com

Indiana

Indianapolis
Community Cancer Center East
Status: Active
Contact: Site Public Contact
Phone: 317-497-2823
Email: lcheri@ecommunity.com
Community Cancer Center North
Status: Active
Contact: Site Public Contact
Phone: 317-497-2823
Email: lcheri@ecommunity.com
Community Cancer Center South
Status: Active
Contact: Site Public Contact
Phone: 317-497-2823
Email: lcheri@ecommunity.com

Iowa

Des Moines
Iowa Methodist Medical Center
Status: Active
Contact: Site Public Contact
Phone: 515-241-6727
Mercy Medical Center - Des Moines
Status: Active
Contact: Site Public Contact
Phone: 308-398-6518
Email: clinicaltrials@sfmc-gi.org

Kansas

Kansas City
University of Kansas Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 913-945-7552
Email: ctnursenav@kumc.edu
Overland Park
University of Kansas Cancer Center-Overland Park
Status: Active
Contact: Site Public Contact
Phone: 913-945-7552
Email: ctnursenav@kumc.edu
Westwood
University of Kansas Hospital-Westwood Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 913-945-7552
Email: ctnursenav@kumc.edu
Wichita
Ascension Via Christi Hospitals Wichita
Status: Active
Contact: Site Public Contact
Phone: 800-362-0070
Email: Keisha.humphries@ascension.org

Kentucky

Lexington
University of Kentucky / Markey Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 859-257-3379
Louisville
The James Graham Brown Cancer Center at University of Louisville
Status: Active
Contact: Site Public Contact
Phone: 502-562-3429

Massachusetts

Boston
Boston Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 617-638-8265
Burlington
Lahey Hospital and Medical Center
Status: Active
Contact: Site Public Contact
Phone: 781-744-3421
Email: cancerclinicaltrials@lahey.org

Michigan

Ann Arbor
Saint Joseph Mercy Hospital
Status: Active
Contact: Site Public Contact
Phone: 734-712-3671
Email: stephanie.couch@stjoeshealth.org
University of Michigan Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-865-1125
Bay City
McLaren Cancer Institute-Bay City
Status: Active
Contact: Site Public Contact
Phone: 313-576-9790
Email: ctoadmin@karmanos.org
Brighton
Saint Joseph Mercy Brighton
Status: Active
Contact: Site Public Contact
Phone: 734-712-3671
Email: stephanie.couch@stjoeshealth.org
Brownstown
Henry Ford Cancer Institute-Downriver
Status: Active
Contact: Site Public Contact
Phone: 313-916-3721
Email: CTOResearch@hfhs.org
Canton
Saint Joseph Mercy Canton
Status: Active
Contact: Site Public Contact
Phone: 734-712-3671
Email: stephanie.couch@stjoeshealth.org
Clarkston
McLaren Cancer Institute-Clarkston
Status: Active
Contact: Site Public Contact
Phone: 313-576-9790
Email: ctoadmin@karmanos.org
Clinton Township
Henry Ford Macomb Hospital-Clinton Township
Status: Active
Contact: Site Public Contact
Phone: 313-916-3721
Email: CTOResearch@hfhs.org
Detroit
Henry Ford Hospital
Status: Active
Contact: Site Public Contact
Phone: 313-916-3721
Email: CTOResearch@hfhs.org
Wayne State University / Karmanos Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 313-576-9790
Email: ctoadmin@karmanos.org
Farmington Hills
Weisberg Cancer Treatment Center
Status: Active
Contact: Site Public Contact
Phone: 313-576-9790
Email: ctoadmin@karmanos.org
Flint
McLaren Cancer Institute-Flint
Status: Active
Contact: Site Public Contact
Phone: 313-576-9790
Email: ctoadmin@karmanos.org
Singh and Arora Hematology Oncology PC
Status: Active
Contact: Site Public Contact
Phone: 313-576-9790
Email: ctoadmin@karmanos.org
Lansing
McLaren-Greater Lansing
Status: Active
Contact: Site Public Contact
Phone: 313-576-9790
Email: ctoadmin@karmanos.org
Mid-Michigan Physicians-Lansing
Status: Active
Contact: Site Public Contact
Phone: 313-576-9790
Email: ctoadmin@karmanos.org
Lapeer
McLaren Cancer Institute-Lapeer Region
Status: Active
Contact: Site Public Contact
Phone: 313-576-9790
Email: ctoadmin@karmanos.org
Mount Clemens
McLaren Cancer Institute-Macomb
Status: Active
Contact: Site Public Contact
Phone: 313-576-9790
Email: ctoadmin@karmanos.org
Petoskey
McLaren Cancer Institute-Northern Michigan
Status: Active
Contact: Site Public Contact
Phone: 313-576-9790
Email: ctoadmin@karmanos.org
Port Huron
McLaren-Port Huron
Status: Active
Contact: Site Public Contact
Phone: 313-576-9790
Email: ctoadmin@karmanos.org
West Bloomfield
Henry Ford West Bloomfield Hospital
Status: Active
Contact: Site Public Contact
Phone: 313-916-3721
Email: CTOResearch@hfhs.org

Minnesota

Bemidji
Sanford Joe Lueken Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 218-333-5000
Email: OncologyClinicalTrialsFargo@sanfordhealth.org
Duluth
Miller-Dwan Hospital
Status: Active
Contact: Site Public Contact
Phone: 218-786-3308
Email: CancerTrials@EssentiaHealth.org
Fridley
Unity Hospital
Status: Active
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Rochester
Mayo Clinic
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 855-776-0015
Saint Cloud
Coborn Cancer Center at Saint Cloud Hospital
Status: Active
Contact: Site Public Contact
Phone: 877-229-4907
Email: coborncancercenter@centracare.com
Saint Paul
Regions Hospital
Status: Active
Contact: Site Public Contact
Phone: 952-993-1517
Email: mmcorc@healthpartners.com

Missouri

Cape Girardeau
Saint Francis Medical Center
Status: Active
Contact: Site Public Contact
Phone: 573-334-2230
Email: sfmc@sfmc.net
Creve Coeur
Siteman Cancer Center at West County Hospital
Status: Active
Contact: Site Public Contact
Phone: 800-600-3606
Email: info@siteman.wustl.edu
Saint Louis
Washington University School of Medicine
Status: Active
Contact: Site Public Contact
Phone: 800-600-3606
Email: info@siteman.wustl.edu
Saint Peters
Siteman Cancer Center at Saint Peters Hospital
Status: Active
Contact: Site Public Contact
Phone: 800-600-3606
Email: info@siteman.wustl.edu

Montana

Kalispell
Kalispell Regional Medical Center
Status: Active
Contact: Site Public Contact
Phone: 406-969-6060
Email: mccinfo@mtcancer.org

Nebraska

Grand Island
CHI Health Saint Francis
Status: Active
Contact: Site Public Contact
Phone: 308-398-6518
Email: clinicaltrials@sfmc-gi.org

New Hampshire

Lebanon
Dartmouth Hitchcock Medical Center
Status: Active
Contact: Site Public Contact
Phone: 800-639-6918
Email: cancer.research.nurse@dartmouth.edu

New Jersey

Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Site Public Contact
Phone: 212-639-7592
Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Site Public Contact
Phone: 212-639-7592
Montvale
Memorial Sloan Kettering Bergen
Status: Active
Contact: Site Public Contact
Phone: 212-639-7592

New Mexico

Albuquerque
University of New Mexico Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 505-925-0366
Email: LByatt@nmcca.org

New York

Bronx
James J Peters VA Medical Center
Status: Active
Contact: Site Public Contact
Phone: 718-584-9000
Email: kl2965@cumc.columbia.edu
Montefiore Medical Center - Moses Campus
Status: Active
Contact: Site Public Contact
Phone: 718-379-6866
Email: aaraiza@montefiore.org
Buffalo
Roswell Park Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 800-767-9355
Email: askroswell@roswellpark.org
Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Site Public Contact
Phone: 212-639-7592
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 212-639-7592
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 212-305-6361
Email: nr2616@cumc.columbia.edu
Rochester
University of Rochester
Status: Active
Contact: Site Public Contact
Phone: 585-275-5830
Stony Brook
Stony Brook University Medical Center
Status: Active
Contact: Site Public Contact
Phone: 800-862-2215
Syracuse
State University of New York Upstate Medical University
Status: Active
Contact: Site Public Contact
Phone: 315-464-5476
Uniondale
Memorial Sloan Kettering Nassau
Status: Active
Contact: Site Public Contact
Phone: 212-639-7592
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Site Public Contact
Phone: 212-639-7592

North Carolina

Charlotte
Atrium Health Pineville / LCI-Pineville
Status: Active
Contact: Site Public Contact
Phone: 980-442-2000
Carolinas Medical Center / Levine Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 800-804-9376
Concord
Atrium Health Cabarrus / LCI-Concord
Status: Active
Contact: Site Public Contact
Phone: 800-804-9376
Hendersonville
Margaret R Pardee Memorial Hospital
Status: Active
Contact: Site Public Contact
Phone: 828-696-4716
Email: karen.morris@unchealth.unc.edu
Monroe
Atrium Health Union / LCI-Union
Status: Active
Contact: Site Public Contact
Phone: 980-442-2000

North Dakota

Fargo
Sanford Roger Maris Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 701-234-6161
Email: OncologyClinicalTrialsFargo@sanfordhealth.org

Ohio

Canton
Aultman Health Foundation
Status: Active
Contact: Site Public Contact
Phone: 330-363-7274
Email: ClinicalReserachDept@aultman.com
Chardon
Geauga Hospital
Status: Active
Contact: Site Public Contact
Phone: 800-641-2422
Email: CTUReferral@UHhospitals.org
Cincinnati
University of Cincinnati / Barrett Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 513-558-4553
Email: uchealthnews@uc.edu
Cleveland
Case Western Reserve University
Status: Active
Contact: Site Public Contact
Phone: 800-641-2422
Email: CTUReferral@UHhospitals.org
Columbus
Ohio State University Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-293-5066
Email: Jamesline@osumc.edu
Sylvania
ProMedica Flower Hospital
Status: Active
Contact: Site Public Contact
Phone: 419-824-1842
West Chester
University Pointe
Status: Active
Contact: Site Public Contact
Email: clinicaltrials@ucphysicians.com

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: Active
Contact: Site Public Contact
Phone: 405-271-8777
Email: ou-clinical-trials@ouhsc.edu

Oregon

Corvallis
Good Samaritan Hospital
Status: Active
Contact: Site Public Contact
Phone: 541-768-4352
Email: stmock@samhealth.org
Portland
Kaiser Permanente Northwest
Status: Active
Contact: Site Public Contact
Phone: 503-335-2400
Email: information@kpchr.org
Providence Portland Medical Center
Status: Active
Contact: Site Public Contact
Phone: 503-215-2614
Email: CanRsrchStudies@providence.org

Pennsylvania

Abington
Abington Memorial Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 215-481-2402
Chadds Ford
Christiana Care Health System-Concord Health Center
Status: Active
Contact: Site Public Contact
Phone: 302-623-4450
Email: KDempsey@christianacare.org
Danville
Geisinger Medical Center
Status: Active
Contact: Site Public Contact
Phone: 570-271-5251
Email: HemonCCTrials@geisinger.edu
Hershey
Penn State Milton S Hershey Medical Center
Status: Active
Contact: Site Public Contact
Phone: 717-531-3779
Email: CTO@hmc.psu.edu
Lewisburg
Geisinger Medical Oncology-Lewisburg
Status: Active
Contact: Site Public Contact
Phone: 570-374-8555
Email: HemonCCTrials@geisinger.edu
Philadelphia
Fox Chase Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 215-728-4790
Pittsburgh
Allegheny General Hospital
Status: Active
Contact: Site Public Contact
Phone: 877-284-2000
UPMC-Shadyside Hospital
Status: Active
Contact: Site Public Contact
Phone: 412-621-2334
Sayre
Guthrie Medical Group PC-Robert Packer Hospital
Status: Active
Contact: Site Public Contact
Phone: 800-836-0388
West Reading
Reading Hospital
Status: Active
Contact: Site Public Contact
Phone: 610-988-9323
Wilkes-Barre
Geisinger Wyoming Valley / Henry Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 570-271-5251
Email: HemonCCTrials@geisinger.edu
Willow Grove
Abington Memorial Hospital-Asplundh Cancer Pavilion
Status: Active
Contact: Site Public Contact
Phone: 215-481-2402

South Carolina

Charleston
Medical University of South Carolina
Status: Active
Contact: Site Public Contact
Phone: 843-792-9321
Email: hcc-clinical-trials@musc.edu
Greer
Gibbs Cancer Center-Pelham
Status: Active
Contact: Site Public Contact
Phone: 864-560-6104
Email: kmertz-rivera@gibbscc.org
Rock Hill
Rock Hill Radiation Therapy Center
Status: Active
Contact: Site Public Contact
Phone: 800-804-9376
Spartanburg
Spartanburg Medical Center
Status: Active
Contact: Site Public Contact
Phone: 864-560-6104
Email: kmertz-rivera@gibbscc.org

South Dakota

Sioux Falls
Sanford USD Medical Center - Sioux Falls
Status: Active
Contact: Site Public Contact
Phone: 605-312-3320
Email: OncologyClinicalTrialsSF@SanfordHealth.org

Vermont

Saint Johnsbury
Norris Cotton Cancer Center-North
Status: Active
Contact: Site Public Contact
Phone: 802-473-4100

Virginia

Charlottesville
University of Virginia Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 434-243-6303
Email: PAS9E@virginia.edu
Norfolk
Sentara Norfolk General Hospital
Status: Active
Contact: Site Public Contact
Phone: 757-388-2406
Richmond
Virginia Commonwealth University / Massey Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 804-628-1914
Email: klcampbell@vcu.edu

Washington

Seattle
University of Washington Medical Center
Status: Active
Contact: Site Public Contact
Phone: 800-804-8824

West Virginia

Morgantown
West Virginia University Healthcare
Status: Active
Contact: Site Public Contact
Phone: 304-293-7374
Email: cancertrialsinfo@hsc.wvu.edu

Wisconsin

Antigo
Langlade Hospital and Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 715-623-9869
Email: Juli.Alford@aspirus.org
La Crosse
Gundersen Lutheran Medical Center
Status: Active
Contact: Site Public Contact
Phone: 608-775-2385
Email: cancerctr@gundersenhealth.org
Menomonee Falls
Community Memorial Hospital
Status: Active
Contact: Site Public Contact
Phone: 262-257-5100
Milwaukee
Medical College of Wisconsin
Status: Active
Contact: Site Public Contact
Phone: 414-805-3666
Zablocki Veterans Administration Medical Center
Status: Active
Contact: Site Public Contact
Phone: 888-469-6614
Mukwonago
ProHealth D N Greenwald Center
Status: Active
Contact: Site Public Contact
Email: research.institute@phci.org
Oconomowoc
ProHealth Oconomowoc Memorial Hospital
Status: Active
Contact: Site Public Contact
Phone: 262-928-7878
Waukesha
UW Cancer Center at ProHealth Care
Status: Active
Contact: Site Public Contact
Phone: 262-928-5539
Email: Chanda.miller@phci.org
Wausau
Aspirus Regional Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 877-405-6866
West Bend
The Alyce and Elmore Kraemer Cancer Care Center
Status: Active
Contact: Site Public Contact
Phone: 866-680-0505

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the safety of radiotherapy (RT) with concurrent and adjuvant anti-PD-L1 therapy (MEDI4736 [durvalumab]) is safe in patients with locoregionally advanced head and neck cancer (HNC) who have a contraindication to cisplatin. (Lead-in)

II. To test the hypothesis that concurrent RT and anti-PD-L1 therapy improves progression free survival (PFS) compared to standard therapy (RT with concurrent cetuximab) in patients with locoregionally advanced HNC who have a contraindication to cisplatin. (Phase II)

III. To test the hypothesis that concurrent RT and anti-PD-L1 therapy improves overall survival compared to standard therapy (RT with concurrent cetuximab) in patients with locoregionally advanced HNC who have a contraindication to cisplatin. (Phase III)

SECONDARY OBJECTIVES:

I. To compare toxicity using Common Terminology Criteria for Adverse Events (CTCAE) and Patient Reported Outcomes (PRO)-CTCAE between patients treated with RT + anti-PD-L1 therapy versus RT/cetuximab.

II. To test the effect of anti-PD-L1 therapy in the subpopulation of patients with tumors that overexpress PD-L1.

III. To compare overall survival, response (at 4-month fludeoxyglucose F-18 [FDG]-positron emission tomography [PET]-computed tomography [CT]), locoregional failure, distant metastasis, and competing mortality in the two arms by known risk factors, including p16 status and omega score.

IV. To test the hypothesis that MEDI4736 (durvalumab) therapy arm will have less decline in the physical function domain of European Organization for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30 version 3.0) based on the change in score from baseline to 12 months from end of RT, compared to the cetuximab-RT arm in patients with locoregionally advanced HNC who have a contraindication to cisplatin.

V. To test the hypothesis that MEDI4736 (durvalumab) therapy arm at 1 year (from end of RT) will have less decline in swallowing related quality of life (QOL) using the M. D. Anderson Dysphagia Inventory (MDADI) total composite score, based on the change in score from baseline to 12 months from end of RT, compared to the cetuximab-RT arm in patients who are medically unfit for cisplatin.

VI. To compare swallowing related performance and function short and long term using the Performance Status Scale for Head & Neck Cancer Patients (PSS-HN).

VII. To evaluate gastrostomy tube retention rates between arms.

EXPLORATORY OBJECTIVES:

I. To test the hypothesis that radiation combined with MEDI4736 (durvalumab) enhances the adaptive immune response using three types of immunophenotyping compared to radiation combined with cetuximab.

II. To compare overall QOL short term (end RT-8 months) and long term (12-24 months from end of RT) between arms using the EORTC QLQ-C30 version 3.0/HN35.

III. To evaluate swallowing related QOL short term (end RT-8 months) and long term (12-24 months from end of RT) using the EORTC Head and Neck (HN)35 swallowing domain and MDADI (subscales) between arms in patients with locoregionally advanced HNC who have a contraindication to cisplatin.

IV. To evaluate patient reported fatigue using the fatigue items in the EORTC QLQ and PRO-CTCAE.

V. To compare clinician and patient reported toxicity using CTCAE and PRO CTCAE.

VI. To explore health utilities between cetuximab and MEDI4736 (durvalumab) RT using the European Quality of Life 5 Dimensional-5 Level (EQ5D-5L).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive cetuximab intravenously (IV) weekly over 60-120 minutes. Treatment repeats every week for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Beginning 5-7 days after first cetuximab dose, patients undergo intensity modulated radiation therapy (IMRT) 5 fractions per week for up to 7 weeks.

ARM II: Patients receive durvalumab IV over 60 minutes every 4 weeks. Treatment repeats every 4 weeks for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Beginning week 2, patients undergo IMRT 5 fractions per week for up to 7 weeks.

After completion of study treatment, patients are followed up at 1 month, every 4 months for 1 year, every 6 months for 2 years, then annually thereafter.

Trial Phase & Type

Trial Phase

Phase II/III

Trial Type

Treatment

Lead Organization

Lead Organization
NRG Oncology

Principal Investigator
Loren K. Mell

Trial IDs

Primary ID NRG-HN004
Secondary IDs NCI-2017-01522
Clinicaltrials.gov ID NCT03258554