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ACTIVE NOT RECRUITING

NCT03952585

PHASE2/PHASE3

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

Sponsor: National Cancer Institute (NCI)

View on ClinicalTrials.gov

Summary

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. Chemotherapy drugs, 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.

Official title: A Randomized Phase II/III Trial of De-Intensified Radiation Therapy for Patients With Early-Stage, P16-Positive, Non-Smoking Associated Oropharyngeal Cancer

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

384

Start Date

2019-10-09

Completion Date

2026-12-11

Last Updated

2026-04-09

Healthy Volunteers

Conditions

Basaloid Squamous Cell Carcinoma Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 Oropharyngeal Squamous Cell Carcinoma Papillary Squamous Cell Carcinoma Pathologic Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 Pathologic Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 Squamous Cell Carcinoma

Interventions

PROCEDURE

Biopsy Procedure

Undergo tissue biopsy

PROCEDURE

Biospecimen Collection

Undergo blood sample collection

DRUG

Cisplatin

Given IV

PROCEDURE

Computed Tomography

Undergo CT

OTHER

Fludeoxyglucose F-18

Receive FDG

RADIATION

Image Guided Radiation Therapy

Undergo IGRT

RADIATION

Intensity-Modulated Radiation Therapy

Undergo IMRT

PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

BIOLOGICAL

Nivolumab

Given IV

PROCEDURE

Positron Emission Tomography

Undergo PET

OTHER

Quality-of-Life Assessment

Ancillary studies

OTHER

Questionnaire Administration

Ancillary studies

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 * Note: If p16 result is equivocal, positive HPV deoxyribonucleic acid (DNA) test of tumor specimen is acceptable and fulfills the eligibility criteria * 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 with contrast 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 * Age \>= 18 * 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 for the hepatitis, 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 centered below the level of the cricoid cartilage * 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 (494)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Banner University Medical Center - Tucson

Tucson, Arizona, United States

University of Arizona Cancer Center-North Campus

Tucson, Arizona, United States

Kaiser Permanente-Deer Valley Medical Center

Antioch, California, United States

PCR Oncology

Arroyo Grande, California, United States

Sutter Auburn Faith Hospital

Auburn, California, United States

Sutter Cancer Centers Radiation Oncology Services-Auburn

Auburn, California, United States

AIS Cancer Center at San Joaquin Community Hospital

Bakersfield, California, United States

Tower Cancer Research Foundation

Beverly Hills, California, United States

Sutter Cancer Centers Radiation Oncology Services-Cameron Park

Cameron Park, California, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Kaiser Permanente Dublin

Dublin, California, United States

UC San Diego Health System - Encinitas

Encinitas, California, United States

Kaiser Permanente-Fremont

Fremont, California, United States

Fresno Cancer Center

Fresno, California, United States

Kaiser Permanente-Fresno

Fresno, California, United States

City of Hope at Irvine Lennar

Irvine, California, United States

UC San Diego Moores Cancer Center

La Jolla, California, United States

City of Hope Antelope Valley

Lancaster, California, United States

Los Angeles General Medical Center

Los Angeles, California, United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

Fremont - Rideout Cancer Center

Marysville, California, United States

Kaiser Permanente-Modesto

Modesto, California, United States

Palo Alto Medical Foundation-Camino Division

Mountain View, California, United States

Kaiser Permanente Oakland-Broadway

Oakland, California, United States

Kaiser Permanente-Oakland

Oakland, California, United States

Palo Alto Medical Foundation Health Care

Palo Alto, California, United States

Stanford Cancer Institute Palo Alto

Palo Alto, California, United States

Kaiser Permanente-Rancho Cordova Cancer Center

Rancho Cordova, California, United States

Kaiser Permanente- Marshall Medical Offices

Redwood City, California, United States

Kaiser Permanente-Richmond

Richmond, California, United States

Rohnert Park Cancer Center

Rohnert Park, California, United States

Kaiser Permanente-Roseville

Roseville, California, United States

Sutter Cancer Centers Radiation Oncology Services-Roseville

Roseville, California, United States

Sutter Roseville Medical Center

Roseville, California, United States

The Permanente Medical Group-Roseville Radiation Oncology

Roseville, California, United States

Kaiser Permanente Downtown Commons

Sacramento, California, United States

Sutter Medical Center Sacramento

Sacramento, California, United States

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Kaiser Permanente-South Sacramento

Sacramento, California, United States

South Sacramento Cancer Center

Sacramento, California, United States

UC San Diego Medical Center - Hillcrest

San Diego, California, United States

Naval Medical Center -San Diego

San Diego, California, United States

Kaiser Permanente-San Francisco

San Francisco, California, United States

UCSF Medical Center-Mission Bay

San Francisco, California, United States

Kaiser Permanente-Santa Teresa-San Jose

San Jose, California, United States

Stanford Cancer Center South Bay

San Jose, California, United States

Kaiser Permanente San Leandro

San Leandro, California, United States

Pacific Central Coast Health Center-San Luis Obispo

San Luis Obispo, California, United States

Kaiser San Rafael-Gallinas

San Rafael, California, United States

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California, United States

Kaiser Permanente-Santa Rosa

Santa Rosa, California, United States

City of Hope South Pasadena

South Pasadena, California, United States

Kaiser Permanente Cancer Treatment Center

South San Francisco, California, United States

Kaiser Permanente-South San Francisco

South San Francisco, California, United States

Kaiser Permanente-Stockton

Stockton, California, United States

Palo Alto Medical Foundation-Sunnyvale

Sunnyvale, California, United States

City of Hope South Bay

Torrance, California, United States

Torrance Memorial Physician Network - Cancer Care

Torrance, California, United States

Torrance Memorial Medical Center

Torrance, California, United States

City of Hope Upland

Upland, California, United States

Kaiser Permanente Medical Center-Vacaville

Vacaville, California, United States

Kaiser Permanente-Vallejo

Vallejo, California, United States

Kaiser Permanente-Walnut Creek

Walnut Creek, California, United States

Rocky Mountain Regional VA Medical Center

Aurora, Colorado, United States

UCHealth University of Colorado Hospital

Aurora, Colorado, United States

Rocky Mountain Cancer Centers-Boulder

Boulder, Colorado, United States

Rocky Mountain Cancer Centers-Penrose

Colorado Springs, Colorado, United States

UCHealth Memorial Hospital Central

Colorado Springs, Colorado, United States

Memorial Hospital North

Colorado Springs, Colorado, United States

AdventHealth Porter

Denver, Colorado, United States

Poudre Valley Hospital

Fort Collins, Colorado, United States

Cancer Care and Hematology-Fort Collins

Fort Collins, Colorado, United States

UCHealth Greeley Hospital

Greeley, Colorado, United States

AdventHealth Littleton

Littleton, Colorado, United States

Medical Center of the Rockies

Loveland, Colorado, United States

AdventHealth Parker

Parker, Colorado, United States

Hartford Hospital

Hartford, Connecticut, United States

Delaware Clinical and Laboratory Physicians PA

Newark, Delaware, United States

Helen F Graham Cancer Center

Newark, Delaware, United States

Medical Oncology Hematology Consultants PA

Newark, Delaware, United States

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, United States

UM Sylvester Comprehensive Cancer Center at Coral Springs

Coral Springs, Florida, United States

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, United States

Jupiter Medical Center

Jupiter, Florida, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Miami Cancer Institute

Miami, Florida, United States

UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida, United States

Orlando Health Cancer Institute

Orlando, Florida, United States

Moffitt Cancer Center-International Plaza

Tampa, Florida, United States

Moffitt Cancer Center - McKinley Campus

Tampa, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

Moffitt Cancer Center at Wesley Chapel

Wesley Chapel, Florida, United States

Grady Health System

Atlanta, Georgia, United States

Emory University Hospital Midtown

Atlanta, Georgia, United States

Hawaii Cancer Care Inc - Waterfront Plaza