Reduced-Dose Intensity-Modulated Radiation Therapy With or Without Cisplatin in Treating Patients With Advanced Oropharyngeal Cancer
Stage III Oropharyngeal Squamous Cell Carcinoma, Stage IVA Oropharyngeal Squamous Cell Carcinoma, Stage IVB Oropharyngeal Squamous Cell Carcinoma
About this trial
This is an interventional treatment trial for Stage III Oropharyngeal Squamous Cell Carcinoma
Eligibility Criteria
Inclusion Criteria
Step 1: Registration:
- Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma (including the histological variants papillary squamous cell carcinoma and basaloid squamous cell carcinoma) 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. 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.
- Immunohistochemical staining for p16 must be performed on tissue, and this tissue must be submitted for central review. Fine needle aspiration (FNA) biopsy specimens may be used as the sole diagnostic tissue if formalin-fixed paraffin-embedded cell block material is available for p16 immunohistochemistry. FNA specimens prepared with adequate p16 testing in this manner are acceptable to submit for central review. If the p16 preparation is not adequate, additional specimens will be required to establish p16 status. Centers are encouraged to contact the pathology chairs for clarification.
Clinical stage T1-T2, N1-N2b or T3, N0-N2b (AJCC, 7th ed.) including no distant metastases based on the following diagnostic workup:
- General history and physical examination within 56 days prior to registration;
- Fiberoptic exam with laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) within 70 days prior to registration;
One of the following combinations of imaging is required within 56 days prior to registration:
- A computed tomography (CT) scan of the neck (with contrast) and a chest CT scan (with or without contrast);
- or an MRI of the neck (with contrast) and a chest CT scan (with or without contrast);
- or a CT scan of neck (with contrast) and a PET/CT of neck and chest (with or without contrast);
- or an MRI of the neck (with contrast) and a PET/CT of neck and chest (with or without contrast).
Note: A CT scan of neck and/or a PET/CT 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) × 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 56 days prior to registration;
- Age ≥ 18;
- The trial is open to both genders;
Adequate hematologic function within 14 days prior to registration, defined as follows:
- Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3;
- Platelets ≥ 100,000 cells/mm3;
- Hemoglobin (Hgb) ≥ 8.0 g/dl; Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.
Adequate renal function within 14 days prior to registration, defined as follows:
• Serum creatinine (Cr) < 1.5 mg/dl or creatinine clearance (CC) ≥ 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula:
- CC male = [(140 - age) x (wt in kg)] / [(Serum Cr mg/dl) x (72)]
- CC female = 0.85 x (CC male)
Adequate hepatic function within 14 days prior to registration defined as follows:
- Bilirubin < 2 mg/dl;
- Aspartate transaminase (AST) or alanine transaminase (ALT) < 3 x the upper limit of normal.
- Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential;
- Patients who are HIV positive but have no prior Acquired Immune Deficiency Syndrome (AIDS) -defining illness and have CD4 cells of at least 350/mm3 are eligible. HIV-positive patients must not have multi-drug resistant HIV infection or other concurrent AIDS-defining conditions. Patients must not be sero-positive for Hepatitis B (Hepatitis B surface antigen positive or anti-hepatitis B core antigen positive) or sero-positive for Hepatitis C (anti-Hepatitis C antibody positive). However, patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B).
- The patient must provide study-specific informed consent prior to study entry, including consent for mandatory submission of tissue for required, central p16 review.
Patients who speak English (or read one of the languages for which a translation is available (see Section 10.2) must consent to complete the mandatory dysphagia-related patient reported instrument (MDADI). If the patient cannot understand spoken English and reads only languages not available in the MDADI translations, the patient can still participate in the trial, as this has been factored into the trial statistics. For all other patients, the MDADI is mandatory as it is included in the primary endpoint to be studied.
Step 2: Randomization:
- p16 positive by immunohistochemistry (defined as greater than 70% strong nuclear or nuclear and cytoplasmic staining of tumor cells), confirmed by central pathology review; (see Section 10.1 for details).
Exclusion Criteria
Step 1: Registration:
- 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 (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;
- Definitive clinical or radiologic evidence of metastatic disease or adenopathy below the clavicles;
- Gross total excision of both primary and nodal disease with curative intent; 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) (for example, 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;
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; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol other than those requested in Section 3.2.10.
- Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition with immune compromise greater than that noted in Inclusion Criterion 13; 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.
- Pregnancy; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
- Prior allergic reaction to cisplatin.
Sites / Locations
- University of Alabama at Birmingham Cancer Center
- Banner MD Anderson Cancer Center
- Banner University Medical Center - Tucson
- Alta Bates Summit Medical Center-Herrick Campus
- Mills-Peninsula Medical Center
- Sutter Cancer Centers Radiation Oncology Services-Cameron Park
- City of Hope Comprehensive Cancer Center
- Marin General Hospital
- UC San Diego Moores Cancer Center
- Kaiser Permanente Los Angeles Medical Center
- Memorial Medical Center
- Kaiser Permanente Oakland-Broadway
- UC Irvine Health/Chao Family Comprehensive Cancer Center
- Palo Alto Medical Foundation Health Care
- Stanford Cancer Institute Palo Alto
- Kaiser Permanente-Rancho Cordova Cancer Center
- Rohnert Park Cancer Center
- Sutter Cancer Centers Radiation Oncology Services-Roseville
- The Permanente Medical Group-Roseville Radiation Oncology
- Sutter Medical Center Sacramento
- University of California Davis Comprehensive Cancer Center
- South Sacramento Cancer Center
- Saint Helena Hospital
- Naval Medical Center -San Diego
- UCSF Medical Center-Mount Zion
- Stanford Cancer Center South Bay
- Kaiser Permanente Medical Center - Santa Clara
- City of Hope South Pasadena
- Kaiser Permanente Cancer Treatment Center
- Palo Alto Medical Foundation-Sunnyvale
- Gene Upshaw Memorial Tahoe Forest Cancer Center
- John Muir Medical Center-Walnut Creek
- University of Colorado Hospital
- Rocky Mountain Cancer Centers-Boulder
- Penrose-Saint Francis Healthcare
- Swedish Medical Center
- Poudre Valley Hospital
- North Colorado Medical Center
- Parker Adventist Hospital
- Yale University
- Christiana Care Health System-Christiana Hospital
- Beebe Health Campus
- Memorial Regional Hospital/Joe DiMaggio Children's Hospital
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- Miami Cancer Institute
- Memorial Hospital West
- Moffitt Cancer Center
- Cleveland Clinic-Weston
- Grady Health System
- Emory University Hospital Midtown
- Piedmont Hospital
- Emory University Hospital/Winship Cancer Institute
- Emory Saint Joseph's Hospital
- Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
- Queen's Medical Center
- The Cancer Center of Hawaii-Liliha
- Saint Alphonsus Cancer Care Center-Boise
- Northwestern University
- John H Stroger Jr Hospital of Cook County
- Decatur Memorial Hospital
- NorthShore University HealthSystem-Evanston Hospital
- NorthShore University HealthSystem-Glenbrook Hospital
- NorthShore University HealthSystem-Highland Park Hospital
- Loyola University Medical Center
- Radiation Oncology Associates PC
- Parkview Hospital Randallia
- Memorial Hospital of South Bend
- University of Kansas Cancer Center
- Lawrence Memorial Hospital
- Olathe Medical Center
- University of Kansas Cancer Center-Overland Park
- Ascension Via Christi Hospitals Wichita
- The James Graham Brown Cancer Center at University of Louisville
- Jewish Hospital Medical Center Northeast
- Greater Baltimore Medical Center
- Boston Medical Center
- Lahey Hospital and Medical Center
- Saint Joseph Mercy Hospital
- University of Michigan Comprehensive Cancer Center
- Henry Ford Cancer Institute-Downriver
- Henry Ford Macomb Hospital-Clinton Township
- Henry Ford Hospital
- Mercy Health Saint Mary's
- Saint Mary Mercy Hospital
- Mercy Health Mercy Campus
- Lakeland Medical Center Saint Joseph
- Henry Ford West Bloomfield Hospital
- Mercy Hospital
- Coborn Cancer Center at Saint Cloud Hospital
- Park Nicollet Clinic - Saint Louis Park
- Regions Hospital
- United Hospital
- Saint Francis Regional Medical Center
- Siteman Cancer Center at West County Hospital
- North Kansas City Hospital
- The University of Kansas Cancer Center-South
- The University of Kansas Cancer Center-North
- The University of Kansas Cancer Center-Lee's Summit
- Delbert Day Cancer Institute at PCRMC
- Washington University School of Medicine
- Mercy Hospital Saint Louis
- Siteman Cancer Center at Saint Peters Hospital
- Mercy Hospital Springfield
- CoxHealth South Hospital
- Billings Clinic Cancer Center
- Benefis Healthcare- Sletten Cancer Institute
- Community Medical Hospital
- CHI Health Saint Francis
- Nebraska Methodist Hospital
- Alegent Health Bergan Mercy Medical Center
- Alegent Health Lakeside Hospital
- University of Nebraska Medical Center
- Radiation Oncology Centers of Nevada Central
- Renown Regional Medical Center
- Saint Mary's Regional Medical Center
- Wentworth-Douglass Hospital
- Dartmouth Hitchcock Medical Center
- Memorial Sloan Kettering Basking Ridge
- Saint Barnabas Medical Center
- Virtua Memorial
- Virtua Voorhees
- University of New Mexico Cancer Center
- Memorial Sloan Kettering Commack
- Memorial Sloan Kettering Westchester
- Memorial Sloan Kettering Cancer Center
- Memorial Sloan Kettering Nassau
- Dickstein Cancer Treatment Center
- Mission Hospital Inc-Memorial Campus
- Vidant Oncology-Kinston
- NHRMC Radiation Oncology - Supply
- NHRMC Radiation Oncology - 16th Street
- UHHS-Chagrin Highlands Medical Center
- Geauga Hospital
- University of Cincinnati/Barrett Cancer Center
- Case Western Reserve University
- Cleveland Clinic Cancer Center/Fairview Hospital
- Cleveland Clinic Foundation
- Ohio State University Comprehensive Cancer Center
- Mercy Cancer Center-Elyria
- Cleveland Clinic Cancer Center Independence
- Hillcrest Hospital Cancer Center
- UH Seidman Cancer Center at Lake Health Mentor Campus
- UH Seidman Cancer Center at Southwest General Hospital
- University Hospitals Parma Medical Center
- North Coast Cancer Care
- UH Seidman Cancer Center at Firelands Regional Medical Center
- Cleveland Clinic Cancer Center Strongsville
- ProMedica Flower Hospital
- University Pointe
- UHHS-Westlake Medical Center
- Cleveland Clinic Wooster Family Health and Surgery Center
- University of Oklahoma Health Sciences Center
- Mercy Hospital Oklahoma City
- Legacy Mount Hood Medical Center
- Abington Memorial Hospital
- UPMC-Heritage Valley Health System Beaver
- UPMC Cancer Centers - Arnold Palmer Pavilion
- Penn State Milton S Hershey Medical Center
- UPMC-Johnstown/John P. Murtha Regional Cancer Center
- UPMC Cancer Center at UPMC McKeesport
- UPMC-Coraopolis/Heritage Valley Radiation Oncology
- Fox Chase Cancer Center
- UPMC-Saint Margaret
- UPMC-Shadyside Hospital
- UPMC-Passavant Hospital
- UPMC Cancer Center at UPMC Northwest
- UPMC Uniontown Hospital Radiation Oncology
- UPMC Washington Hospital Radiation Oncology
- Reading Hospital
- Medical University of South Carolina
- Greenville Health System Cancer Institute-Faris
- Greenville Health System Cancer Institute-Eastside
- Greenville Health System Cancer Institute-Greer
- Greenville Health System Cancer Institute-Seneca
- Spartanburg Medical Center
- Greenville Health System Cancer Institute-Spartanburg
- Tennessee Cancer Specialists-Dowell Springs
- University of Texas Medical Branch
- M D Anderson Cancer Center
- MD Anderson in Katy
- UTMB Cancer Center at Victory Lakes
- MD Anderson League City
- MD Anderson in The Woodlands
- Intermountain Medical Center
- McKay-Dee Hospital Center
- Utah Cancer Specialists-Salt Lake City
- Huntsman Cancer Institute/University of Utah
- Norris Cotton Cancer Center-North
- University of Virginia Cancer Center
- Virginia Commonwealth University/Massey Cancer Center
- Tacoma/Valley Radiation Oncology Centers-Gig Harbor
- Virginia Mason Medical Center
- Tacoma/Valley Radiation Oncology Centers-Jackson Hall
- MultiCare Tacoma General Hospital
- Tacoma/Valley Radiation Oncology Centers-Saint Joe's
- Legacy Salmon Creek Hospital
- Saint Vincent Hospital Cancer Center Green Bay
- Saint Vincent Hospital Cancer Center at Saint Mary's
- UW Cancer Center Johnson Creek
- Gundersen Lutheran Medical Center
- University of Wisconsin Hospital and Clinics
- Community Memorial Hospital
- Medical College of Wisconsin
- Ascension All Saints Hospital
- HSHS Saint Nicholas Hospital
- The Alyce and Elmore Kraemer Cancer Care Center
- Aspirus UW Cancer Center
- Tom Baker Cancer Centre
- Cross Cancer Institute
- BCCA-Vancouver Island Cancer Centre
- Juravinski Cancer Centre at Hamilton Health Sciences
- Kingston Health Sciences Centre
- Odette Cancer Centre- Sunnybrook Health Sciences Centre
- University Health Network-Princess Margaret Hospital
- Windsor Regional Cancer Centre
- CHUM - Hopital Notre-Dame
- McGill University Department of Oncology
- Jewish General Hospital
- Allan Blair Cancer Centre
- Saskatoon Cancer Centre
- Saint Lukes Hospital
- King Faisal Specialist Hospital and Research Centre
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
IMRT 6 weeks + cisplatin
IMRT 5 weeks
IMRT 6 weeks with concurrent cisplatin
IMRT 5 weeks