De-intensified Radiation Therapy with Chemotherapy (Cisplatin) or Immunotherapy (Nivolumab) in Treating Patients with Early-Stage, HPV-Positive, Non-Smoking Associated Oropharyngeal Cancer

Status: Active

Description

This phase II / III trial studies how well a reduced dose of radiation therapy works with nivolumab compared to cisplatin in treating patients with human papillomavirus (HPV)-positive oropharyngeal cancer that is early in its growth and may not have spread to other parts of the body (early-stage), and is not associated with smoking. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial is being done to see if a reduced dose of radiation therapy and nivolumab works as well as standard dose radiation therapy and cisplatin in treating patients with oropharyngeal cancer.

Eligibility Criteria

Inclusion Criteria

  • Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma (including the histological variants papillary squamous cell carcinoma and basaloid squamous cell carcinoma but not neuroendocrine phenotype) of the oropharynx (tonsil, base of tongue, soft palate, or oropharyngeal walls); cytologic diagnosis from a cervical lymph node is sufficient in the presence of clinical evidence of a primary tumor in the oropharynx. Clinical evidence should be documented, may consist of palpation, imaging, or endoscopic evaluation, and should be sufficient to estimate the size of the primary (for T stage)
  • Patients must have clinically or radiographically evident measurable disease at the primary site or at nodal stations. Simple tonsillectomy or local excision of the primary without removal of nodal disease is permitted, as is excision removing gross nodal disease but with intact primary site. Limited neck dissections retrieving =< 4 nodes are permitted and considered as non-therapeutic nodal excisions
  • P16-positive based on local site immunohistochemical tissue staining (defined as greater than 70% strong diffuse nuclear or nuclear and cytoplasmic staining of tumor cells). Fine needle aspiration (FNA) biopsy specimens may be used as the sole diagnostic tissue. Centers are encouraged to contact the pathology chair for clarification * Note: Institutions must screen patients, whose tumors must be p16-positive by immunohistochemistry (IHC) in order to be eligible for the trial using a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. A rigorous laboratory accreditation process similar to the United States (U.S.) CLIA certification, such as the provincial accreditation status offered by the Ontario Laboratory Accreditation (OLA) Program in Canada, the College of American Pathologists (CAP), or an equivalent accreditation in other countries, is acceptable. The p16-positive results must be reported on the pathology report being submitted
  • Clinical stage T1-2, N1, M0 (American Joint Committee on Cancer [AJCC], 8th edition [ed.]) or T3, N0-N1, M0 (AJCC, 8th ed.) including no distant metastases based on the following diagnostic workup: * General history and physical examination within 56 days prior to registration; * Exam with laryngopharyngoscopy (mirror or in office direct procedure acceptable) within 70 days prior to registration; * One of the following imaging studies is required within 56 days prior to registration: ** FDG-PET/CT of the neck and chest (with or without contrast); FDG-PET/CT scan is strongly preferred and highly recommended to be used for eligibility OR ** Chest CT (with or without contrast) * One of the following imaging studies is required within 28 days prior to registration: ** A diagnostic CT scan of neck (with contrast and of diagnostic quality) OR ** An magnetic resonance imaging (MRI) of the neck (with contrast and of diagnostic quality) ** Note: A diagnostic quality CT or MRI or FDG-PET/CT scan of neck performed for the purposes of radiation planning may serve as both staging and planning tools
  • Patients must provide their personal smoking history prior to registration. The lifetime cumulative history cannot exceed 10 pack-years. The following formula is used to calculate the pack-years during the periods of smoking in the patient’s life; the cumulative total of the number of pack-years during each period of active smoking is the lifetime cumulative history * Number of pack-years = [Frequency of smoking (number of cigarettes per day) x duration of cigarette smoking (years)] / 20 * Note: Twenty cigarettes is considered equivalent to one pack. The effect of non-cigarette tobacco products on the survival of patients with p16-positive oropharyngeal cancers is undefined. While there are reportedly increased risks of head and neck cancer associated with sustained heavy cigar and pipe use (Wyss 2013), such sustained use of non-cigarette products is unusual and does not appear to convey added risk with synchronous cigarette smoking. Cigar and pipe tobacco consumption is therefore not included in calculating the lifetime pack-years. Marijuana consumption is likewise not considered in this calculation. There is no clear scientific evidence regarding the role of chewing tobacco-containing products in this disease, although this is possibly more concerning given the proximity of the oral cavity and oropharynx. In any case, investigators are discouraged from enrolling patients with a history of very sustained use (such as several years or more) of non-cigarette tobacco products alone
  • Zubrod performance status of 0-1 within 14 days prior to registration
  • Absolute neutrophil count >= 1,500/mcL (within 14 days prior to registration)
  • Platelets >= 100,000/mcL (within 14 days prior to registration)
  • Hemoglobin >= 8.0 g/dL (within 14 days prior to registration) (Note: use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dL is acceptable)
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 14 days prior to registration)
  • Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x institutional ULN (within 14 days prior to registration)
  • Serum creatinine =< 1.5 x ULN OR creatinine clearance (CrCl) >= 50 mL/min (if using the Cockcroft-Gault formula) (within 14 days prior to registration)
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B)
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. * Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy
  • For women of childbearing potential (WOCBP), negative serum or urine pregnancy test within 24 hours prior to registration * Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
  • Women of childbearing potential (WOCBP) and men who are sexually active with WOCBP must be willing to use an adequate method of contraception during and after treatment
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
  • Only English, Spanish, or French speaking patients are eligible to participate as these are the only languages for which the mandatory dysphagia-related patient reported instrument (MDADI) is available

Exclusion Criteria

  • Clinical stages T0; T4; T1-2, N0; or any N2 (AJCC, 8th ed)
  • Recurrent disease
  • Definitive clinical or radiologic evidence of metastatic disease or adenopathy below the clavicles
  • Cancers considered to be from an oral cavity site (oral tongue, floor mouth, alveolar ridge, buccal or lip), or the nasopharynx, hypopharynx, or larynx, even if p16-positive, or histologies of adenosquamous, verrucous, or spindle cell carcinomas
  • Carcinoma of the neck of unknown primary site origin (T0 is ineligible, even if p16-positive)
  • Radiographically matted nodes, defined as 3 abutting nodes with loss of the intervening fat plane
  • Supraclavicular nodes, defined as nodes visualized on the same axial imaging slice as the clavicle
  • Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. In other words, to participate in this protocol, the patient must have clinically or radiographically evident gross disease for which disease response can be assessed
  • Patients with simultaneous primary cancers or separate bilateral primary tumor sites are excluded with the exception of patients with bilateral tonsil cancers
  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) (of note, the exclusion applies only for invasive cancers such that carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
  • Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
  • History of severe hypersensitivity reaction to any monoclonal antibody.
  • Severe, active co-morbidity defined as follows: * Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months * Transmural myocardial infarction within the last 6 months * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects * Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition with immune compromise greater than that noted; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients * Condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of registration. Inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease * Patients with active autoimmune disease requiring systemic treatment (i.e. disease modifying agents, corticosteroids, or immunosuppressive drugs) should be excluded. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), rheumatoid arthritis, connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn’s, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease * Note: Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)
  • Patients who are pregnant, nursing, or expecting to conceive or father children
  • Prior allergic reaction to cisplatin

Locations & Contacts

Arizona

Tucson
Banner University Medical Center - Tucson
Status: Active
Contact: Site Public Contact
Email: aselegue@email.arizona.edu

California

Duarte
City of Hope Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-826-4673
Email: becomingapatient@coh.org
Palo Alto
Stanford Cancer Institute Palo Alto
Status: Active
Contact: Site Public Contact
Phone: 650-498-7061
Email: ccto-office@stanford.edu
Sacramento
Sutter Medical Center Sacramento
Status: Active
Contact: Site Public Contact
Phone: 415-209-2686
Email: bernicl@sutterhealth.org
San Francisco
UCSF Medical Center-Mission Bay
Status: Active
Contact: Site Public Contact
Phone: 877-827-3222

Delaware

Newark
Christiana Care Health System-Christiana Hospital
Status: Active
Contact: Site Public Contact
Phone: 302-623-4450
Email: KDempsey@christianacare.org
Delaware Clinical and Laboratory Physicians PA
Status: Active
Contact: Site Public Contact
Phone: 302-623-4450
Email: KDempsey@christianacare.org
Helen F Graham Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 302-623-4450
Email: KDempsey@christianacare.org
Medical Oncology Hematology Consultants PA
Status: Active
Contact: Site Public Contact
Phone: 302-623-4450
Email: KDempsey@christianacare.org

Florida

Orlando
UF Cancer Center at Orlando Health
Status: Active
Contact: Site Public Contact
Phone: 321-841-7246
Email: CancerClinicalTrials@orlandohealth.com
Tampa
Moffitt Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-679-0775
Email: canceranswers@moffitt.org
Moffitt Cancer Center - McKinley Campus
Status: Active
Contact: Site Public Contact
Phone: 800-679-0775
Email: canceranswers@moffitt.org
Moffitt Cancer Center-International Plaza
Status: Active
Contact: Site Public Contact
Phone: 800-679-0775
Email: canceranswers@moffitt.org

Georgia

Atlanta
Emory University Hospital Midtown
Status: Active
Contact: Site Public Contact
Phone: 888-946-7447
Grady Health System
Status: Active
Contact: Site Public Contact
Phone: 404-489-9164

Illinois

Bloomington
Illinois CancerCare-Bloomington
Status: Active
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com
Canton
Illinois CancerCare-Canton
Status: Active
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com
Carthage
Illinois CancerCare-Carthage
Status: Active
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com
Centralia
Centralia Oncology Clinic
Status: Active
Contact: Site Public Contact
Phone: 217-876-4740
Email: rhamrick@dmhhs.org
Chicago
Northwestern University
Status: Active
Contact: Site Public Contact
Phone: 312-695-1301
Email: cancer@northwestern.edu
Decatur
Cancer Care Specialists of Illinois - Decatur
Status: Active
Contact: Site Public Contact
Phone: 217-876-4740
Email: rhamrick@dmhhs.org
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
Eureka
Illinois CancerCare-Eureka
Status: Active
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com
Galesburg
Illinois CancerCare-Galesburg
Status: Active
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com
Kewanee
Illinois CancerCare-Kewanee Clinic
Status: Active
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com
Macomb
Illinois CancerCare-Macomb
Status: Active
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com
Ottawa
Illinois CancerCare-Ottawa Clinic
Status: Active
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com
Pekin
Illinois CancerCare-Pekin
Status: Active
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com
Peoria
Illinois CancerCare-Peoria
Status: Active
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com
Methodist Medical Center of Illinois
Status: Active
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com
Peru
Illinois CancerCare-Peru
Status: Active
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com
Princeton
Illinois CancerCare-Princeton
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
Southern Illinois University School of Medicine
Status: Active
Contact: Site Public Contact
Phone: 217-545-7929
Springfield Clinic
Status: Active
Contact: Site Public Contact
Phone: 800-444-7541

Iowa

Clive
Medical Oncology and Hematology Associates-West Des Moines
Status: Active
Contact: Site Public Contact
Phone: 308-398-6518
Email: clinicaltrials@sfmc-gi.org
Mercy Cancer Center-West Lakes
Status: Active
Contact: Site Public Contact
Phone: 308-398-6518
Email: clinicaltrials@sfmc-gi.org
Des Moines
Broadlawns Medical Center
Status: Active
Contact: Site Public Contact
Phone: 515-282-2200
Iowa Lutheran Hospital
Status: Active
Contact: Site Public Contact
Phone: 515-241-8704
Iowa Methodist Medical Center
Status: Active
Contact: Site Public Contact
Phone: 515-241-6727
Medical Oncology and Hematology Associates-Des Moines
Status: Active
Contact: Site Public Contact
Phone: 515-282-2921
Medical Oncology and Hematology Associates-Laurel
Status: Active
Contact: Site Public Contact
Phone: 308-398-6518
Email: clinicaltrials@sfmc-gi.org
Mercy Medical Center - Des Moines
Status: Active
Contact: Site Public Contact
Phone: 308-398-6518
Email: clinicaltrials@sfmc-gi.org
West Des Moines
Mercy Medical Center-West Lakes
Status: Active
Contact: Site Public Contact
Phone: 308-398-6518
Email: clinicaltrials@sfmc-gi.org
Methodist West Hospital
Status: Active
Contact: Site Public Contact
Phone: 515-343-1000

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

Kentucky

Lexington
University of Kentucky / Markey Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 859-257-3379
Louisville
Jewish Hospital
Status: Active
Contact: Site Public Contact
Phone: 308-398-6518
Email: clinicaltrials@sfmc-gi.org
Norton Brownsboro Hospital and Medical Campus
Status: Active
Contact: Site Public Contact
Phone: 412-339-5294
Email: Roster@nrgoncology.org
Norton Hospital Pavilion and Medical Campus
Status: Active
Contact: Site Public Contact
Phone: 502-629-2500
The James Graham Brown Cancer Center at University of Louisville
Status: Active
Contact: Site Public Contact
Phone: 502-562-3429

Louisiana

Baton Rouge
Louisiana Hematology Oncology Associates LLC
Status: Active
Contact: Site Public Contact
Phone: 225-215-1353
Email: clinicalresearch@marybird.com
LSU Health Baton Rouge-North Clinic
Status: Active
Contact: Site Public Contact
Phone: 225-215-1353
Email: clinicalresearch@marybird.com
Mary Bird Perkins Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 225-215-1353
Email: clinicalresearch@marybird.com
Our Lady of the Lake Physicians Group - Medical Oncology
Status: Active
Contact: Site Public Contact
Phone: 225-215-1353
Email: clinicalresearch@marybird.com

Maine

Bath
MaineHealth Coastal Cancer Treatment Center
Status: Active
Contact: Site Public Contact
Phone: 412-339-5294
Email: Roster@nrgoncology.org
Biddeford
MaineHealth / SMHC Cancer Care and Blood Disorders-Biddeford
Status: Active
Contact: Site Public Contact
Email: LLemire@mmc.org
Portland
Maine Medical Center-Bramhall Campus
Status: Active
Contact: Site Public Contact
Phone: 207-885-7565
Rockport
Penobscot Bay Medical Center
Status: Active
Contact: Site Public Contact
Phone: 207-396-8670
Email: ClinicalResearch@mmc.org
Sanford
MaineHealth / SMHC Cancer Care and Blood Disorders-Sanford
Status: Active
Contact: Site Public Contact
Email: LLemire@mmc.org
MaineHealth Cancer Care Center of York County
Status: Active
Contact: Site Public Contact
Phone: 207-459-1600
Scarborough
Maine Medical Center- Scarborough Campus
Status: Active
Contact: Site Public Contact
Phone: 207-396-8090
Email: wrighd@mmc.org
South Portland
Maine Medical Partners - South Portland
Status: Active
Contact: Site Public Contact
Phone: 207-396-8670
Email: ClinicalResearch@mmc.org

Maryland

Baltimore
Greater Baltimore Medical Center
Status: Active
Contact: Site Public Contact
Phone: 443-849-3706

Michigan

Ann Arbor
Saint Joseph Mercy Hospital
Status: Active
Contact: Site Public Contact
Phone: 734-712-3671
Email: stephanie.couch@stjoeshealth.org
Brighton
Saint Joseph Mercy Brighton
Status: Active
Contact: Site Public Contact
Phone: 734-712-3671
Email: stephanie.couch@stjoeshealth.org
Canton
Saint Joseph Mercy Canton
Status: Active
Contact: Site Public Contact
Phone: 734-712-3671
Email: stephanie.couch@stjoeshealth.org
Chelsea
Saint Joseph Mercy Chelsea
Status: Active
Contact: Site Public Contact
Phone: 734-712-3671
Email: stephanie.couch@stjoeshealth.org

Minnesota

Bemidji
Sanford Joe Lueken Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 218-333-5000
Email: OncologyClinicalTrialsFargo@sanfordhealth.org
Saint Cloud
Coborn Cancer Center at Saint Cloud Hospital
Status: Active
Contact: Site Public Contact
Phone: 877-229-4907
Email: coborncancercenter@centracare.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
Kansas City
The University of Kansas Cancer Center-North
Status: Active
Contact: Site Public Contact
Phone: 913-945-7552
Email: ctnursenav@kumc.edu
Rolla
Delbert Day Cancer Institute at PCRMC
Status: Active
Contact: Site Public Contact
Phone: 573-458-8776
Email: kaysmith@phelpshealth.org
Mercy Clinic-Rolla-Cancer and Hematology
Status: Active
Contact: Site Public Contact
Phone: 573-458-7504
Email: jrichards@research.pcrmc.com
Saint Louis
Siteman Cancer Center-South County
Status: Active
Contact: Site Public Contact
Phone: 800-600-3606
Email: info@siteman.wustl.edu
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

Great Falls
Benefis Healthcare- Sletten Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 406-969-6060
Email: mccinfo@mtcancer.org

New York

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

North Carolina

Gastonia
CaroMont Regional Medical Center
Status: Active
Contact: Site Public Contact
Phone: 704-834-2810
Email: tammy.cozad@caromonthealth.org

North Dakota

Bismarck
Sanford Bismarck Medical Center
Status: Active
Contact: Site Public Contact
Phone: 701-323-5760
Email: OncologyClinicalTrialsFargo@sanfordhealth.org
Fargo
Sanford Broadway Medical Center
Status: Active
Contact: Site Public Contact
Phone: 701-323-5760
Email: OncologyClinicalTrialsFargo@sanfordhealth.org
Sanford Roger Maris Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 701-234-6161
Email: OncologyClinicalTrialsFargo@sanfordhealth.org

Ohio

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
Cleveland Clinic Cancer Center / Fairview Hospital
Status: Active
Contact: Site Public Contact
Phone: 866-223-8100
Email: CancerAnswer@ccf.org
Cleveland Clinic Foundation
Status: Active
Contact: Site Public Contact
Phone: 866-223-8100
Email: CancerAnswer@ccf.org
Mansfield
Cleveland Clinic Cancer Center Mansfield
Status: Active
Contact: Site Public Contact
Phone: 866-223-8100
Email: CancerAnswer@ccf.org
Mayfield Heights
Hillcrest Hospital Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 866-223-8100
Email: CancerAnswer@ccf.org
Mentor
UH Seidman Cancer Center at Lake Health Mentor Campus
Status: Active
Contact: Site Public Contact
Phone: 800-641-2422
Email: CTUReferral@UHhospitals.org
Middleburg Heights
UH Seidman Cancer Center at Southwest General Hospital
Status: Active
Contact: Site Public Contact
Phone: 800-641-2422
Email: CTUReferral@UHhospitals.org
Sandusky
North Coast Cancer Care
Status: Active
Contact: Site Public Contact
Phone: 866-223-8100
Email: CancerAnswer@ccf.org
Strongsville
Cleveland Clinic Cancer Center Strongsville
Status: Active
Contact: Site Public Contact
Phone: 866-223-8100
Email: CancerAnswer@ccf.org
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
Wooster
Cleveland Clinic Wooster Family Health and Surgery Center
Status: Active
Contact: Site Public Contact
Phone: 866-223-8100
Email: CancerAnswer@ccf.org

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

Clackamas
Clackamas Radiation Oncology Center
Status: Active
Contact: Site Public Contact
Phone: 503-215-2614
Email: CanRsrchStudies@providence.org
Newberg
Providence Newberg Medical Center
Status: Active
Contact: Site Public Contact
Phone: 503-215-2614
Email: CanRsrchStudies@providence.org
Portland
Providence Portland Medical Center
Status: Active
Contact: Site Public Contact
Phone: 503-215-2614
Email: CanRsrchStudies@providence.org
Providence Saint Vincent Medical Center
Status: Active
Contact: Site Public Contact
Phone: 503-215-2614
Email: CanRsrchStudies@providence.org

Pennsylvania

Chadds Ford
Christiana Care Health System-Concord Health Center
Status: Active
Contact: Site Public Contact
Phone: 302-623-4450
Email: KDempsey@christianacare.org
Gettysburg
Adams Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 877-441-7957
Philadelphia
Fox Chase Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 215-728-4790
York
WellSpan Health-York Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 877-441-7957
WellSpan Health-York Hospital
Status: Active
Contact: Site Public Contact
Phone: 877-441-7957

South Dakota

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

Utah

Farmington
Farmington Health Center
Status: Active
Contact: Site Public Contact
Phone: 888-424-2100
Email: cancerinfo@hci.utah.edu
Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: Active
Contact: Site Public Contact
Phone: 888-424-2100
Email: cancerinfo@hci.utah.edu

Wisconsin

La Crosse
Gundersen Lutheran Medical Center
Status: Active
Contact: Site Public Contact
Phone: 608-775-2385
Email: cancerctr@gundersenhealth.org
Madison
University of Wisconsin Hospital and Clinics
Status: Active
Contact: Site Public Contact
Phone: 800-622-8922
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
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 demonstrate non-inferiority in terms of progression-free survival (PFS) of concurrent reduced-dose radiation therapy (RT) with cisplatin or concurrent reduced-dose radiation therapy with nivolumab to the current standard of care (standard-dose RT with cisplatin). (Phase II)

II. To demonstrate co-primary endpoints of non-inferiority of PFS and superiority of quality of life (QOL) as measured by the MD Anderson Dysphagia Inventory (MDADI) of concurrent reduced-dose radiation with cisplatin or concurrent reduced-dose radiation with nivolumab to the current standard of care (standard-dose RT with cisplatin). (Phase III)

SECONDARY OBJECTIVES:

I. To compare patterns of failure (local and regional relapse versus distant) and overall survival between each experimental arm and the control arm.

II. To assess long term PFS, overall survival, and toxicity between each experimental arm and the control arm.

III. To determine acute and late toxicity profiles as measured by the Common Terminology Criteria for Adverse Events (CTCAE).

IV. To explore the symptomatic adverse events (AEs) for tolerability of each treatment arm as measured by the Patient-Reported Outcomes (PRO)-CTCAE.

V. To compare changes in patient-reported outcomes (Hearing Handicap Inventory for Adults-Screening [HHIA-S], European Organization for Research and Treatment of Cancer [EORTC]-Quality of Life Questionnaire [QLQ]30) between each experimental arm and the control arm.

VI. To assess the association of fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) at baseline with locoregional control and PFS.

VII. To estimate the negative predictive value of the 12-14 weeks post-radiation therapy (RT) FDG-PET/CT in terms of locoregional control rates and PFS rates at 1 and 2 years.

EXPLORATORY OBJECTIVES:

I. To collect blood and tissue specimens for future translation research.

II. To optimize radiotherapy treatment plan quality assurance methodology for radiotherapy planning and imaging.

III. To compare changes in patient-reported outcomes (European Quality of Life Five Dimension Five Level Scale [EQ-5D-5L]) between each experimental arm and the control arm.

IV. To collect Modified Barium Swallow (MBS) data for future review and analysis.

V. To assess the locoregional control rates and PFS for patients with FDG-PET/CT at 12-14 weeks post-radiation.

OUTLINE:

PHASE II: Patients are randomized to 1 of 3 arms.

ARM I: Patients undergo intensity modulated radiation therapy (IMRT) or image-guided radiation therapy (IGRT) over 6 fractions per week and receive cisplatin intravenously (IV) over 30-60 minutes on days 1 and 22. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo reduced dose IMRT or IGRT once daily (QD) over 5 fractions per week and receive cisplatin IV over 30-60 minutes on days 1 and 22. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity.

ARM III: Beginning 1 week prior to radiation, patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 weeks (14 days) for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo reduced dose IMRT or IGRT over 6 fractions per week for 5 weeks in the absence of disease progression or unacceptable toxicity.

PHASE III: Patients are randomized to Arm I, Arm II, and/or Arm III.

After completion of study treatment, patients are followed up at 12-14 weeks, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Trial Phase & Type

Trial Phase

Phase II/III

Trial Type

Treatment

Lead Organization

Lead Organization
NRG Oncology

Principal Investigator
Sue Sun Yom

Trial IDs

Primary ID NRG-HN005
Secondary IDs NCI-2019-03015
Clinicaltrials.gov ID NCT03952585