Radiation Therapy With Cisplatin or Cetuximab in Treating Patients With Oropharyngeal Cancer
Head and Neck Cancer, Precancerous Condition
About this trial
This is an interventional treatment trial for Head and Neck Cancer focused on measuring stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, human papilloma virus infection
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) of the oropharynx (tonsil, base of tongue, soft palate, or oropharyngeal walls).
- Patients must be positive for p16, determined by central review prior to randomization.
- 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. Fine needle aspirations of the neck are insufficient due to limited tissue for retrospective central review. Biopsy specimens from the primary or nodes measuring at least 3-5 mm are required.
Clinical stage T1-2, N2a-N3 or T3-4, any N (AJCC, 7th ed.; see Appendix III), including no distant metastases, based upon the following minimum diagnostic workup:
- General history and physical examination by a radiation oncologist and medical oncologist within 8 weeks prior to registration;
- Examination by an ear, nose, and throat (ENT) or head and neck surgeon, including laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) within 8 weeks prior to registration;
One of the following combinations of imaging is required within 8 weeks prior to registration:
- A computerized tomography (CT) scan of the neck (with contrast) and a chest CT scan (with or without contrast);
- or a magnetic resonance imaging (MRI) scan of the neck (with contrast) and a chest CT scan (with or without contrast);
- or a CT scan of neck (with contrast) and a positron emission tomography (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 radiation planning and read by a radiologist may serve as both staging and planning tools.
- Zubrod Performance Status 0-1 within 2 weeks prior to registration
- Age ≥ 18;
Complete blood count (CBC)/differential obtained within 2 weeks prior to registration on study, with adequate bone marrow function, 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 hepatic function, defined as follows:
- Bilirubin < 2 mg/dl within 2 weeks prior to registration;
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x the upper limit of normal within 2 weeks prior to registration;
Adequate renal function, defined as follows:
• Serum creatinine < 1.5 mg/dl within 2 weeks prior to registration or creatinine clearance (CCr) ≥ 50 ml/min within 2 weeks prior to registration determined by 24-hour collection or estimated by Cockcroft-Gault formula:
CCr male = [(140 - age) x (wt in kg)] [(Serum Cr mg/dl) x (72)] CCr female = 0.85 x (CCr male)
- Patients must provide their smoking history (for stratification) via the computer-assisted self interview (CASI) head and neck risk factor survey tool.
- Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential;
- Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study and until at least 60 days following the last study treatment.
- Patients who are human immunodeficiency virus (HIV) positive but have no prior acquired immune deficiency syndrome (AIDS) -defining illness and have CD4 cells of at least 350/mm3 are eligible. Patient HIV status must be known prior to registration. 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). HIV-positive patients must not have multi-drug resistant HIV infection or other concurrent AIDS-defining conditions.
- Patient must provide study specific informed consent prior to study entry, including consent for mandatory submission of tissue for required, central p16 review and consent to participate in the computer-assisted self interview (CASI) survey questions regarding smoking history.
Exclusion Criteria:
- Cancers considered to be from an oral cavity site (oral tongue, floor mouth, alveolar ridge, buccal or lip), nasopharynx, hypopharynx, or larynx, even if p16 positive, are excluded. Carcinoma of the neck of unknown primary site origin (even if p16 positive) are excluded from participation.
- Stage T1-2, N0-1;
- Distant metastasis or adenopathy below the clavicles;
- 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.
- Simultaneous primaries or bilateral tumors;
- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 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:
- 9.1 Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
- 9.2 Transmural myocardial infarction within the last 6 months;
- 9.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
- 9.4 Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration;
- 9.5 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.
- 9.6 Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition with immune compromise greater than that noted in Section 3.1.13; 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 or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
- Prior allergic reaction to cisplatin or cetuximab;
- Prior cetuximab or other anti-EGFR therapy.
Sites / Locations
- Providence Cancer Center
- Auburn Radiation Oncology
- Roy and Patricia Disney Family Cancer Center at Providence Saint Joseph Medical Center
- Radiation Oncology Centers - Cameron Park
- Mercy Cancer Center at Mercy San Juan Medical Center
- Enloe Cancer Center at Enloe Medical Center
- City of Hope Comprehensive Cancer Center
- Rebecca and John Moores UCSD Cancer Center
- Kaiser Permanente - Division of Research - Oakland
- Rohnert Park Cancer Center
- Radiation Oncology Center - Roseville
- Radiological Associates of Sacramento Medical Group, Incorporated
- Mercy General Hospital
- UCSF Helen Diller Family Comprehensive Cancer Center
- Kaiser Permanente Medical Center - South San Francisco
- Solano Radiation Oncology Center
- Rocky Mountain Cancer Centers - Aurora
- Boulder Community Hospital
- Penrose Cancer Center at Penrose Hospital
- Porter Adventist Hospital
- Swedish Medical Center
- McKee Medical Center
- North Suburban Medical Center
- George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus
- CCOP - Christiana Care Health Services
- North Broward Medical Center
- Integrated Community Oncology Network
- Baptist Cancer Institute - Jacksonville
- Integrated Community Oncology Network at Southside Cancer Center
- Baptist Medical Center South
- University of Miami Sylvester Comprehensive Cancer Center - Miami
- Integrated Community Oncology Network - Orange Park
- Florida Hospital Cancer Institute at Florida Hospital Orlando
- M.D. Anderson Cancer Center at Orlando
- Florida Cancer Center - Palatka
- Sacred Heart Cancer Center at Sacred Heart Hospital
- Flagler Cancer Center
- H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
- Georgia Cancer Center for Excellence at Grady Memorial Hospital
- Winship Cancer Institute of Emory University
- Northeast Georgia Medical Center
- Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
- Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
- Northwest Community Hospital
- Robert H. Lurie Comprehensive Cancer Center at Northwestern University
- John H. Stroger, Jr. Hospital of Cook County
- University of Chicago Cancer Research Center
- Creticos Cancer Center at Advocate Illinois Masonic Medical Center
- Decatur Memorial Hospital Cancer Care Institute
- Evanston Hospital
- Cardinal Bernardin Cancer Center at Loyola University Medical Center
- Cancer Institute at St. John's Hospital
- Regional Cancer Center at Memorial Medical Center
- St. Francis Hospital and Health Centers - Beech Grove Campus
- Elkhart General Hospital
- Parkview Regional Cancer Center at Parkview Health
- Center for Cancer Care at Goshen General Hospital
- Community Regional Cancer Care at Community Hospital East
- Community Regional Cancer Care at Community Hospital North
- Michiana Hematology-Oncology, PC - South Bend
- Cancer Center at Ball Memorial Hospital
- Memorial Hospital of South Bend
- McFarland Clinic, PC
- John Stoddard Cancer Center at Iowa Methodist Medical Center
- Siouxland Hematology-Oncology Associates, LLP
- Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
- Kansas City Cancer Centers - Southwest
- CCOP - Kansas City
- Lucille P. Markey Cancer Center at University of Kentucky
- James Graham Brown Cancer Center at University of Louisville
- Mary Bird Perkins Cancer Center - Baton Rouge
- CCOP - Ochsner
- Maine Center for Cancer Medicine and Blood Disorders - Scarborough
- Greenebaum Cancer Center at University of Maryland Medical Center
- St. Agnes Hospital Cancer Center
- Lahey Clinic Medical Center - Burlington
- NSMC Cancer Center - Peabody
- Hudner Oncology Center at Saint Anne's Hospital - Fall River
- Saint Joseph Mercy Cancer Center
- Battle Creek Health System Cancer Care Center
- Josephine Ford Cancer Center at Henry Ford Hospital
- Genesys Hurley Cancer Institute
- Butterworth Hospital at Spectrum Health
- Lacks Cancer Center at Saint Mary's Health Care
- Mercy and Unity Cancer Center at Mercy Hospital
- Fairview Southdale Hospital
- Mercy and Unity Cancer Center at Unity Hospital
- Park Nicollet Cancer Center
- Regions Hospital Cancer Care Center
- Regional Cancer Center at Singing River Hospital
- Cancer Institute of Cape Girardeau, LLC
- Kansas City Cancer Centers - South
- Kansas City Cancer Centers - North
- Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
- Barnes-Jewish West County Hospital
- CCOP - St. Louis-Cape Girardeau
- David C. Pratt Cancer Center at St. John's Mercy
- Hulston Cancer Center at Cox Medical Center South
- Billings Clinic - Downtown
- Methodist Estabrook Cancer Center
- Nebraska Medical Center
- Renown Institute for Cancer at Renown Regional Medical Center
- Payson Center for Cancer Care at Concord Hospital
- Seacoast Cancer Center at Wentworth - Douglass Hospital
- Kingsbury Center for Cancer Care at Cheshire Medical Center
- Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
- Monmouth Medical Center
- Frederick R. and Betty M. Smith Cancer Treatment Center
- Cancer Institute of New Jersey at Cooper - Voorhees
- University of New Mexico Cancer Center
- Lourdes Regional Cancer Center
- Highland Hospital of Rochester
- James P. Wilmot Cancer Center at University of Rochester Medical Center
- Mission Hospitals - Memorial Campus
- Blumenthal Cancer Center at Carolinas Medical Center
- Moses Cone Regional Cancer Center at Wesley Long Community Hospital
- Kinston Medical Specialists
- FirstHealth Moore Regional Community Hospital Comprehensive Cancer Center
- Summa Center for Cancer Care at Akron City Hospital
- Barberton Citizens Hospital
- Charles M. Barrett Cancer Center at University Hospital
- Case Comprehensive Cancer Center
- Cleveland Clinic Cancer Center at Fairview Hospital
- Cleveland Clinic Taussig Cancer Center
- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
- Northwest Ohio Oncology Center
- Hillcrest Cancer Center at Hillcrest Hospital
- Lake/University Ireland Cancer Center
- Southwest General Health Center
- St. Charles Mercy Hospital
- Flower Hospital Cancer Center
- St. Anne Mercy Hospital
- Precision Radiotherapy at University Pointe
- UHHS Westlake Medical Center
- Cancer Treatment Center
- Oklahoma University Cancer Institute
- Natalie Warren Bryant Cancer Center at St. Francis Hospital
- Clackamas Radiation Oncology Center
- Dubs Cancer Center at Rogue Valley Medical Center
- Providence Cancer Center at PMCC
- Providence Cancer Center at Providence Portland Medical Center
- Providence St. Vincent Medical Center
- Knight Cancer Institute at Oregon Health and Science University
- Rosenfeld Cancer Center at Abington Memorial Hospital
- Dale and Frances Hughes Cancer Center at Pocono Medical Center
- Adams Cancer Center
- Cherry Tree Cancer Center
- St. Mary Regional Cancer Center
- Fox Chase Cancer Center - Philadelphia
- McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
- York Cancer Center at Apple Hill Medical Center
- Hollings Cancer Center at Medical University of South Carolina
- Cancer Centers of the Carolinas - Faris Road
- CCOP - Greenville
- Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
- Cancer Centers of the Carolinas - Spartanburg
- Rapid City Regional Hospital
- Vanderbilt-Ingram Cancer Center
- University of Texas Medical Branch
- M. D. Anderson Cancer Center at University of Texas
- Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
- Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
- Utah Valley Regional Medical Center - Provo
- Utah Cancer Specialists at UCS Cancer Center
- Huntsman Cancer Institute at University of Utah
- Sentara Cancer Institute at Sentara Norfolk General Hospital
- Coastal Cancer Center at Sentara Virginia Beach General Hospital
- St. Joseph Cancer Center
- CCOP - Virginia Mason Research Center
- Northwest Cancer Specialists at Vancouver Cancer Center
- North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
- Edwards Comprehensive Cancer Center at Cabell Huntington Hospital
- Schiffler Cancer Center at Wheeling Hospital
- Theda Care Cancer Institute
- St. Mary's Hospital Medical Center - Green Bay
- St. Vincent Hospital Regional Cancer Center
- Gundersen Lutheran Center for Cancer and Blood
- University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
- Bay Area Cancer Care Center at Bay Area Medical Center
- Medical College of Wisconsin Cancer Center
- Veterans Affairs Medical Center - Milwaukee
- University of Wisconcin Cancer Center at Aspirus Wausau Hospital
- CancerCare Manitoba
- McGill Cancer Centre at McGill University
Arms of the Study
Arm 1
Arm 2
Active Comparator
Active Comparator
IMRT + Cisplatin
IMRT + Cetuximab
Intensity-modulated radiotherapy (IMRT) with concurrent cisplatin
Intensity-modulated radiotherapy (IMRT) with concurrent cetuximab