Adjuvant Cetuximab and Chemoradiotherapy Using Either Cisplatin or Docetaxel in Treating Patients With Resected Stage III or Stage IV Squamous Cell Carcinoma or Lymphoepithelioma of the Head and Neck

Head and Neck Cancer Clinical Trial

Official title:

A Phase II Randomized Trial Of Surgery Followed By Chemoradiotherapy Plus Cetuximab For Advanced Squamous Cell Carcinoma Of The Head and Neck

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00084318
• Other study ID #: RTOG-0234
• Secondary ID: CDR0000360850
• Status: Completed
• Phase: Phase 2
• Start date: April 2004
• Est. completion date: December 2016

Study information

• Verified date: December 2016
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Cisplatin and docetaxel may make the tumor cells more sensitive to radiation therapy. Combining a monoclonal antibody with chemoradiotherapy and giving them after surgery may kill any remaining tumor cells.

PURPOSE: This randomized phase II trial is studying adjuvant cetuximab given together with chemoradiotherapy using cisplatin to see how well it works compared to adjuvant cetuximab given together with chemoradiotherapy using docetaxel in treating patients with resected stage III or stage IV squamous cell carcinoma (cancer) or lymphoepithelioma of the head and neck.

Description:

OBJECTIVES:

Primary

• Compare disease-free survival of patients with resected stage III or IV squamous cell carcinoma or lymphoepithelioma of the head and neck treated with adjuvant cetuximab in combination with chemoradiotherapy comprising docetaxel vs cisplatin.

Secondary

• Compare the safety and efficacy of these regimens in these patients.

• Compare locoregional control and overall survival rates in patients treated with these regimens.

• Correlate epidermal growth factor receptor (total and phosphorylated), pMAPK, pAKT, Stat-3, Ki-67, cyclo-oxygenase-2, and cyclin B1 expression with outcome in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to Zubrod performance status (0 vs 1), risk category (positive margins vs high risk [i.e., ≥ 2 positive nodes or extracapsular nodal extension]) and use of intensity-modulated radiotherapy (no vs yes). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive cetuximab IV over 2 hours on day 1 (week 1). Patients then receive cetuximab IV over 1 hour and cisplatin IV over 1 hour before radiotherapy on days 8, 15, 22, 29, 36, and 43 (weeks 2-7). Patients undergo radiotherapy once daily, 5 days a week, beginning on day 8 for a total of 6 weeks (weeks 2-7).

• Arm II: Patients receive cetuximab and undergo radiotherapy as in arm I. Patients also receive docetaxel IV over 30 minutes before radiotherapy on days 8, 15, 22, 29, 36, and 43 (weeks 2-7).

Treatment in both arms continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 4 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 230 patients (115 per treatment arm) will be accrued for this study within approximately 29 months.

Other known NCT identifiers

• NCT00414674

Recruitment information / eligibility

• Status: Completed
• Enrollment: 238
• Est. completion date: December 2016
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma of the head and neck meeting the following criteria:

• Site of tumor origin in the oral cavity, oropharynx, larynx, or hypopharynx (excluding lip, nasopharynx, or sinuses)

• Gross total resection must be completed within 7 weeks of randomization, with pathology demonstrating one or more of the following risk factors:

• Histologic extracapsular nodal extension

• Histologic involvement of = 2 regional lymph nodes

• Invasive cancer seen on microscopic evaluation of the resection margin, with no evidence of gross tumor residual.

• Tonsillar cancer patients who undergo transoral excision of all gross tumor are eligible provided extracapsular nodal extension or involvement of = 2 regional lymph nodes is histologically confirmed

• American Joint Committee on Cancer (AJCC) pathological stage III or IV

• No evidence of distant metastases

• No synchronous or concurrent head and neck primary tumors

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count = 2,000/mm^3

• Platelet count = 100,000/mm^3

• Hemoglobin > 8.0 g/dL

Hepatic

• Bilirubin = 1.5 times upper limit of normal (ULN)

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT), and alkaline phosphatase meeting 1 of the following parameters:

• Alkaline phosphatase = ULN AND AST or ALT = 5 times ULN

• Alkaline phosphatase = 2.5 times ULN AND AST or ALT = 1.5 times ULN

• Alkaline phosphatase = 5 times ULN AND AST or ALT = ULN

Renal

• Creatinine = 1.5 mg/dL

Cardiovascular

• No unstable angina

• No uncontrolled hypertension

• No myocardial infarction within the past 6 months (unless successfully treated with coronary artery bypass surgery or percutaneous transluminal coronary angioplasty)

• No uncontrolled arrhythmia

• No congestive heart failure

• No more than 2 heart-related hospitalizations within the past year

• No other active cardiac disease

Pulmonary

• No more than 2 hospitalizations for chronic obstructive pulmonary disease within the past year

Neurologic

• No pre-existing peripheral neuropathy = grade 2

• No uncontrolled seizure disorder

• No active neurological disease

Other

• No prior severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80

• No other invasive malignancy within the past 3 years except nonmelanoma skin cancer

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 3 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior anti-epidermal growth factor receptor antibody therapy

Chemotherapy

• More than 3 years since prior cytotoxic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior head and neck radiotherapy

Surgery

• See Disease Characteristics

Other

• No prior tyrosine kinase inhibitor therapy

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Biological:
• cetuximab
400 mg/m^2 intravenously over 120 minutes on day 1 (week 1) followed by 250 mg/m^2 intravenously over 60 minutes in weeks 2 through 7.

Drug:
• cisplatin
30 mg/m^2 intravenously infused over over 60 minutes in weeks 2 through 7.
• docetaxel
15 mg/m^2 intravenously infused over 30 minutes in weeks 2 through 7.

Radiation:
• radiation therapy
60 Gy (2 Gy once a day, 5 times a week)

Locations

Country	Name	City	State
United States	Rosenfeld Cancer Center at Abington Memorial Hospital	Abington	Pennsylvania
United States	Akron City Hospital	Akron	Ohio
United States	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio
United States	Tulane Cancer Center	Alexandria	Louisiana
United States	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois
United States	St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Mission Hospitals - Memorial Campus	Asheville	North Carolina
United States	Auburn Radiation Oncology	Auburn	California
United States	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Aurora	Colorado
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	St. Joseph Cancer Center	Bellingham	Washington
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Lynn Regional Cancer Center at Boca Raton Community Hospital - Main Center	Boca Raton	Florida
United States	Cancer Research Center at Boston Medical Center	Boston	Massachusetts
United States	Dana-Farber/Brigham and Women's Cancer Center	Boston	Massachusetts
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Long Island College Hospital	Brooklyn	New York
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Providence Saint Joseph Medical Center - Burbank	Burbank	California
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Cancer Institute of New Jersey at Cooper University Hospital - Camden	Camden	New Jersey
United States	Radiation Oncology Centers - Cameron Park	Cameron Park	California
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital	Cape Girardeau	Missouri
United States	Mercy Cancer Center at Mercy San Juan Medical Center	Carmichael	California
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University	Columbus	Ohio
United States	John B. Amos Cancer Center	Columbus	Georgia
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Danville Regional Medical Center	Danville	Virginia
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Wendt Regional Cancer Center at Finley Hospital	Dubuque	Iowa
United States	Veterans Affairs Medical Center - East Orange	East Orange	New Jersey
United States	Dale and Frances Hughes Cancer Center at Pocono Medical Center	East Stroudsburg	Pennsylvania
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Hudner Oncology Center at Saint Anne's Hospital - Fall River	Fall River	Massachusetts
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Michael & Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Bon Secours St. Francis Health System	Greenville	South Carolina
United States	CCOP - Greenville	Greenville	South Carolina
United States	Leo W. Jenkins Cancer Center at ECU Medical School	Greenville	North Carolina
United States	Ingalls Cancer Care Center at Ingalls Memorial Hospital	Harvey	Illinois
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	M.D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska
United States	Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center	Kingsport	Tennessee
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	John D. Cronin Cancer Center	Lexington	Kentucky
United States	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey
United States	Upper Michigan Cancer Center at Marquette General Hospital	Marquette	Michigan
United States	Hillcrest Cancer Center at Hillcrest Hospital	Mayfield Heights	Ohio
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	University of Minnesota Medical Center & Children's Hospital - Fairview	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Providence Holy Cross Cancer Center	Mission Hills	California
United States	Mobile Infirmary Medical Center	Mobile	Alabama
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Cottonwood Hospital Medical Center	Murray	Utah
United States	Saint Peter's University Hospital	New Brunswick	New Jersey
United States	Hospital of Saint Raphael	New Haven	Connecticut
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	CCOP - Bay Area Tumor Institute	Oakland	California
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	Methodist Cancer Center at Methodist Hospital - Omaha	Omaha	Nebraska
United States	M.D. Anderson Cancer Center Orlando	Orlando	Florida
United States	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi
United States	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	Arizona Oncology Services Foundation	Phoenix	Arizona
United States	Mercy Cancer Institute at Mercy Hospital	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University Cancer Institute	Portland	Oregon
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	All Saints Cancer Center at All Saints Healthcare	Racine	Wisconsin
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Reading Hospital and Medical Center	Reading	Pennsylvania
United States	Veterans Affairs Medical Center - Richmond	Richmond	Virginia
United States	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia
United States	Hubert H. Humphrey Cancer Center at North Memorial Medical Center	Robbinsdale	Minnesota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Radiation Oncology Center - Roseville	Roseville	California
United States	Mercy General Hospital	Sacramento	California
United States	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California
United States	University of California Davis Cancer Center	Sacramento	California
United States	CentraCare Clinic - River Campus	Saint Cloud	Minnesota
United States	Coborn Cancer Center	Saint Cloud	Minnesota
United States	Dixie Regional Medical Center - East Campus	Saint George	Utah
United States	Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph	Saint Joseph	Michigan
United States	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri
United States	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri
United States	Siteman Cancer Center at Barnes-Jewish Hospital	Saint Louis	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Health Services	Saint Louis Park	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	Latter Day Saints Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah
United States	Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
United States	Guthrie Cancer Center at Guthrie Clinic Sayre	Sayre	Pennsylvania
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	Virginia G. Piper Cancer Center at Scottsdale Healthcare - Osborn	Scottsdale	Arizona
United States	Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea	Scottsdale	Arizona
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Cancer Institute at St. John's Hospital	Springfield	Illinois
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	St. John's Regional Health Center	Springfield	Missouri
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	Tallahassee Memorial Hospital	Tallahassee	Florida
United States	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	J. Phillip Citta Regional Cancer Center at Community Medical Center	Toms River	New Jersey
United States	Torrance Memorial Medical Center	Torrance	California
United States	Solano Radiation Oncology Center	Vacaville	California
United States	Fox Chase Virtua Health Cancer Program at Virtua West Jersey	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Schiffler Cancer Center at Wheeling Hospital	Wheeling	West Virginia
United States	Forsyth Regional Cancer Center at Forsyth Medical Center	Winston-Salem	North Carolina
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania
United States	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania
United States	York Cancer Center at Apple Hill Medical Center	York	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI), NRG Oncology

Country where clinical trial is conducted

United States, 

References & Publications (2)

Harari PM, Harris J, Kies MS, et al.: Phase II randomized trial of surgery followed by chemoradiation plus cetuximab for high-risk squamous cell carcinoma of the head and neck (RTOG 0234). [Abstract] Int J Radiat Oncol Biol Phys 69 (3 Suppl): A-22, S13, 2

Harari PM, Harris J, Kies MS, Myers JN, Jordan RC, Gillison ML, Foote RL, Machtay M, Rotman M, Khuntia D, Straube W, Zhang Q, Ang K. Postoperative chemoradiotherapy and cetuximab for high-risk squamous cell carcinoma of the head and neck: Radiation Therap — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free Survival	Two-year rates are shown (Kaplan-Meier estimates). Disease-free survival is defined as the time from randomization to local, regional, or distant progression, second primary, or death (event) or last follow-up (censored). Response criteria as follows: No evidence of disease (NED): All patients must have no measurable tumor following surgery; Local-Regional Relapse: Recurrent cancer in the tumor bed and/or neck not clearly attributable to a second primary neoplasm; biopsy confirmation is necessary; Distant Relapse: Clear evidence of distant metastases (lung, bone, brain, etc.); Biopsy is recommended where possible. A solitary lung mass/nodule is considered a second primary neoplasm unless proven otherwise.	From randomization to 2 years
Secondary	Overall Survival	Two-year rates are shown (Kaplan-Meier estimates). Overall survival is defined as the time from randomization to death (event) or last follow-up (censored).	From randomization to 2 years
Secondary	Treatment Tolerance	Tolerability was defined as having received 90% of the radiation dose, 95% of the cetuximab loading dose, and at least 4 weeks of cetuximab and cisplatin or docetaxel at doses 95% of the protocol prescription. The percentage of patients determined to be tolerant of treatment are shown.	From start of treatment to end of treatment (protocol treatment lasts seven weeks).
Secondary	Frequency of Toxicity (Grade 5 and Acute Non-hematologic Grade 4)	Each regimen was monitored for excessive acute toxicity (defined as nonhematologic grade 4 toxicity within 90 days of the start of radiation or any grade 5 toxicity). The target rate was based on the observed rate from RTOG-9501/NCT00002670 of 15%. The unacceptable rate was >30%. [RTOG = Radiation Therapy Oncology Group]	From start of treatment to last follow-up. Analysis occurs at the time of the primary analysis.
Secondary	Frequency of Other Acute and Late Toxicity	Maximum grade toxicity that is definitely, probably, or possibly related to protocol treatment.	From start of treatment to last follow-up. Analysis occurs at the time of the primary endpoint analysis.
Secondary	Local-regional Control	Two-year rate is shown (cumulative incidence estimate). Local-regional failure is defined as the time from randomization to local-regional recurrence (event), death (competing risk), or last follow-up (censored).	From randomization to 2 years
Secondary	Correlation of EGFR (Total and Phosphorylated) pMAPK, pAKT, Stat-3, KI-67, COX-2, and Cyclin B1 Expression With Local-regional Control, and Overall and Disease-free Survival		From randomization to two years