Back to results

Radiation Therapy With Cisplatin or Cetuximab in Treating Patients With Oropharyngeal Cancer

Primary Purpose

Head and Neck Cancer, Precancerous Condition

Status

Active

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

cetuximab

cisplatin

IMRT

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

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:
  1. A computerized tomography (CT) scan of the neck (with contrast) and a chest CT scan (with or without contrast);
  2. or a magnetic resonance imaging (MRI) scan of the neck (with contrast) and a chest CT scan (with or without contrast);
  3. or a CT scan of neck (with contrast) and a positron emission tomography (PET)/CT of neck and chest (with or without contrast);
  4. 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

Arm Type

Active Comparator

Arm Label

IMRT + Cisplatin

IMRT + Cetuximab

Arm Description

Intensity-modulated radiotherapy (IMRT) with concurrent cisplatin

Intensity-modulated radiotherapy (IMRT) with concurrent cetuximab

Outcomes

Primary Outcome Measures

Overall Survival

An event for overall survival is death due to any cause. Survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol endpoint is hazard ratio, which is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.

Secondary Outcome Measures

Progression-free Survival

An event for progression-free survival is local, regional, or distant disease progression or death due to any cause. Progression-free survival time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol endpoint is the distribution of progression-free survival times, for which the hazard ratio is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.

Time to Local-regional Failure

Failure for local-regional failure endpoint was defined as local or regional progression, salvage surgery of the primary tumor with tumor present/unknown, salvage neck dissection with tumor present/unknown > 20 weeks after the end of radiation therapy, death due to study cancer without documented progression, or death due to unknown causes without documented progression; distant metastasis and death due to other causes were considered competing risks. Local-regional failure time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method. The protocol endpoint is the distribution of local-regional failure times, for which the hazard ratio is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.

Time to Distant Metastasis

Failure for distant metastasis endpoint was defined as distant progression; local-regional failure and death due to any cause were considered competing risks. Distant metastasis time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method. The protocol endpoint is the distribution of distant metastasis times, for which the hazard ratio is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.

Time to Secondary Primary Cancer

Failure for second primary endpoint was defined as reporting of a new primary cancer; death due to any cause was considered a competing risk. Second primary time is defined as time from randomization to the date of second primary or last known follow-up (censored). Rates are estimated by the cumulative incidence method. The protocol endpoint is the distribution of second primary cancer times, for which the hazard ratio is reported in the statistical analysis results. Five-year rate is reported simply as summary data; it is not the outcome measure.

Distribution of First Progression Events

The first event type for progression-free survival is counted for each participant. Possible first progression events are local, regional, or distant progression, any combination of these, or death. The frequency table of these events is also referred to as "Pattern of failure."

Percentage of Participants Experiencing Early Death

Early death is defined as death due to adverse event or within 30 days of treatment completion.

Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: During Treatment

Acute adverse events (AE) are defined as occurring within 180 days from the end of treatment. "Treatment-related" means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE

Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: 1 Month After End of Study Treatment

Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: 3 Months After the End of Study Treatment

Percentage of Participants With Acute Grade 3-4 Treatment-related Adverse Events: 6 Months After the End of Study Treatment

Percentage of Participants With Late Grade 3-4 Treatment-related Adverse Events: 1 Year After the End of Study Treatment

Late adverse events (AE) are defined as > 180 days from end of treatment. "Treatment-related" means reported as definitely, probably, or possibly related to protocol treatment. AE were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE

Percentage of Participants With Late Grade 3-4 Treatment-related Adverse Events: 2 Years After the End of Study Treatment

Percentage of Participants With Late Grade 3-4 Treatment-related Adverse Events: 5 Years After the End of Study Treatment

Percentage of Participants With a Feeding Tube at 1 Year

EORTC QLQ-C30 at Baseline, End of Treatment, 3, 6, and 12 Months From End of Treatment.

EORTC QLQ-H&N35 at Baseline, End of Treatment, 3, 6, and 12 Months From End of Treatment.

Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events for Head and Neck (PRO-CTCAE H&N) at Baseline, End of Treatment, 3, 6, and 12 Months From End of Treatment.

EuroQol Five Dimension Scale (EQ-5D) at Baseline, End of Treatment, 3, 6, and 12 Months From End of Treatment.

Work Status Questionnaire at Baseline, End of Treatment, 3, 6, and 12 Months.

Percentage of Patients With Normal/Good Dental Health: Pretreatment

This study utilized a dental effects health scale from 0 (normal) to 4 (life-threatening dental condition). The percentage of participants with a value of 0 or 1 is reported: 0 = "Normal: Edentulous, with no gingival disease"; 1 = "Mild changes/good dental health: mild periodontal inflammation-routine cleaning indicated; < 5 restorations indicated; no extractions indicated." Ten year data is not yet available.

Percentage of Patients With Normal/Good Dental Health: 1 Year After End of Treatment

Percentage of Patients With Normal/Good Dental Health: 2 Years After End of Treatment

Percentage of Patients With Normal/Good Dental Health: 5 Years After End of Treatment

Percentage of Patients With Normal/Good Dental Health: 10 Years After End of Treatment

his study utilized a dental effects health scale from 0 (normal) to 4 (life-threatening dental condition). The percentage of participants with a value of 0 or 1 is reported: 0 = "Normal: Edentulous, with no gingival disease"; 1 = "Mild changes/good dental health: mild periodontal inflammation-routine cleaning indicated; < 5 restorations indicated; no extractions indicated."

Hearing Quality of Life Outcomes as Measured by the Hearing Handicap Inventory for Adults (HHIA-S) at Baseline, End of Treatment and at 3, 6, and 12 Months From End of Treatment.

Behavioral Risk Assessment Survey (BRASS) at Baseline.

Translational Research Analysis

Full Information

NCT ID

NCT01302834

First Posted

February 22, 2011

Last Updated

September 15, 2023

Sponsor

Radiation Therapy Oncology Group

Collaborators

National Cancer Institute (NCI), NRG Oncology

1. Study Identification

Unique Protocol Identification Number

NCT01302834

Brief Title

Radiation Therapy With Cisplatin or Cetuximab in Treating Patients With Oropharyngeal Cancer

Official Title

Phase III Trial of Radiotherapy Plus Cetuximab Versus Chemoradiotherapy in HPV-Associated Oropharynx Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

June 2011 (Actual)

Primary Completion Date

July 12, 2018 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Radiation Therapy Oncology Group

Collaborators

National Cancer Institute (NCI), NRG Oncology

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

RATIONALE: 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 or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether radiation therapy is more effective with cisplatin or cetuximab in treating oropharyngeal cancer. PURPOSE: This phase III trial is studying radiation therapy with cisplatin or cetuximab to see how well it works in treating patients with oropharyngeal cancer.

Detailed Description

OBJECTIVES: Primary To determine whether substitution of cisplatin with cetuximab will result in comparable 5-year overall survival. Secondary To monitor and compare progression-free survival for "safety". To compare patterns of failure (locoregional vs distant). To compare acute toxicity profiles (and overall toxicity burden). To compare overall quality of life (QOL) short-term (< 6 months) and long-term (1 year). To compare QOL Swallowing Domains short-term and long-term. To compare clinician-reported versus patient-reported CTCAE toxicity events. To explore differences in the cost effectiveness of cetuximab as compared to cisplatin. To explore differences in work status and time to return to work. To compare patient-reported changes in hearing. To compare CTCAE v. 4 late toxicity at 1, 2, and 5 years. To evaluate the effect of tobacco exposure (and other exposures) as measured by standardized computer-assisted self interview (CASI) on overall survival and progression-free survival. To pilot CASI collection of patient reported outcomes in a cooperative group setting. To determine whether specific molecular profiles are associated with overall or progression-free survival. To investigate associations between changes in serum biomarkers or human papilloma virus (HPV)-specific cellular immune responses measured at baseline and three months with overall or progression-free survival. OUTLINE: This is a multicenter study. Patients are stratified according to T stage (T1-2 vs T 3-4), N stage (N0-2a vs N2b-3), Zubrod performance status (0 vs 1), and smoking history (≤ 10 pack-years vs > 10 pack-years). Patients are randomized to 1 of 2 treatment arms. Patients may complete quality-of-life questionnaires and risk factors for head and neck cancer surveys at baseline, periodically during study, and at follow-up for 1 year. After completion of study therapy, patients are followed up at 1-3 months, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Head and Neck Cancer, Precancerous Condition

Keywords

stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, human papilloma virus infection

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

987 (Actual)

8. Arms, Groups, and Interventions

Arm Title

IMRT + Cisplatin

Arm Type

Active Comparator

Arm Description

Intensity-modulated radiotherapy (IMRT) with concurrent cisplatin

Arm Title

IMRT + Cetuximab

Arm Type

Active Comparator

Arm Description

Intensity-modulated radiotherapy (IMRT) with concurrent cetuximab

Intervention Type

Biological

Intervention Name(s)

cetuximab

Intervention Description

400 mg/m2 IV 5-7 days before IMRT then 250 mg/m2 IV weekly for 7 weeks

Intervention Type

Drug

Intervention Name(s)

cisplatin

Intervention Description

100 mg/m2 IV on days 1 and 22 of IMRT

Intervention Type

Radiation

Intervention Name(s)

IMRT

Other Intervention Name(s)

intensity-modulated radiotherapy, intensity-modulated radiation therapy

Intervention Description

35 fractions over 6 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 70 Gy.

Primary Outcome Measure Information:

Title

Overall Survival

Description

Time Frame