Induction Chemotherapy Followed By Cetuximab and Radiation in HPV-Associated Resectable Stage III/IV Oropharynx Cancer

NCT01084083 | Completed Phase 2 Results

• 3 other identifiers: CDR0000665170ECOG-E1308U10CA023318
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 121

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as paclitaxel and 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. Radiation therapy uses high energy x-rays to kill tumor cells. Giving paclitaxel, cisplatin, and cetuximab together with radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying paclitaxel, cisplatin, and cetuximab to see how well they work when followed by cetuximab and two different doses of intensity-modulated radiation therapy in treating patients with HPV-associated stage III or stage IV cancer of the oropharynx that can be removed by surgery.

Conditions

Head and Neck Cancer; Precancerous Condition

Keywords

human papilloma virus infection; stage III squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the oropharynx; tongue cancer

Outcome Measures

Primary Outcomes (1)

• 24-month Progression-free Survival

  24-month progression-free survival is defined as the proportion of patients who were alive and progression-free at 24 months post registration. The primary study population for this endpoint is patients who were confirmed post-induction clinical complete response (CR) at their primary sites and subsequently received 5400 cGy radiation therapy to their primary sites.

  assessed within 14 days after delivery of the third cycle of induction therapy, and 8 weeks and 6 months after completion of concurrent therapy, then every 6 months until progression or until 3 years from study entry

Secondary Outcomes (2)

• 24-months Overall Survival

  assessed within 14 days after delivery of the third cycle of induction therapy, and 8 weeks and 6 months after completion of concurrent therapy, then every 6 months until progression or until 3 years from study entry

• Primary Clinical Response Rate

  assessed within 14 days after delivery of the third cycle of induction therapy

Study Arms (2)

Group 1

EXPERIMENTAL

After induction therapy with Paclitaxel and Cisplatin, patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 5 weeks (27 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 6 weeks.

Biological: cetuximab; Radiation: intensity-modulated radiation therapy (IMRT); Drug: Paclitaxel; Drug: Cisplatin

Group 2

EXPERIMENTAL

After induction therapy with Paclitaxel and Cisplatin, patients undergo standard-dose IMRT 5 days per week for approximately 6 weeks (33 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 7 weeks.

Biological: cetuximab; Radiation: intensity-modulated radiation therapy (IMRT); Drug: Paclitaxel; Drug: Cisplatin

Interventions

cetuximab BIOLOGICAL

Given IV

Group 1; Group 2

intensity-modulated radiation therapy (IMRT) RADIATION

Patients undergo low-dose OR standard dose IMRT based on their clinical response to induction therapy

Group 1; Group 2

Paclitaxel DRUG

Given IV, 90 mg/m\^2 on days 1, 8 and 15

Also known as: Abraxane, Taxol

Group 1; Group 2

Cisplatin DRUG

Given IV, 75 mg/m\^2 on day 1

Also known as: Platinol

Group 1; Group 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed squamous cell carcinoma of the oropharynx as determined by Hematoxylin and eosin (H\&E) staining
• Newly diagnosed disease
• Resectable disease OR disease that is expected to become resectable after study treatment
• Stage III, IVA, or IVB disease as determined by imaging studies (computed tomography (CT) scan with IV contrast or magnetic resonance imaging (MRI) required) and a complete head and neck exam
• Paraffin-embedded tumor specimen available for central confirmation of HPV-associated disease as determined by H\&E staining and in-situ hybridization (ISH) for HPV-16 and immunohistochemistry (IHC) for p16
• HPV-associated disease is defined as p16 IHC-positive and/or HPV-16 ISH-positive
• Non-HPV-associated disease is defined as p16 IHC-negative
• NOTE: If there is limited tumor material, p16 IHC will be performed before HPV-16 ISH
• Measurable disease of the primary tumor or nodes by clinical and radiographic methods, defined as a lesion that is ≥ 2 cm in at least one dimension by clinical exam AND by radiographic exam with CT scan or MRI (or a lesion that is ≥ 1 cm in at least one dimension if the radiographic exam utilizes spiral CT scan)
• No primary tumor or nodal metastasis fixed to the carotid artery, skull base, or cervical spine
• No evidence of distant metastases
• Eastern Cooperative Oncology Group performance status 0-1
• Granulocytes ≥ 1,000/mm\^3
• Platelet count ≥ 100,000/mm\^3
• Total serum bilirubin ≤ 1.5 mg/dL

You may not qualify if:

• Prior chemotherapy
• Prior radiotherapy above the clavicles
• Prior surgery with curative intent for this disease (complete head and neck exam with biopsy allowed)
• Prior therapy specifically and directly targeting the EGFR pathway
• Prior severe infusion reaction to a monoclonal antibody
• Uncontrolled diabetes, uncontrolled infection despite antibiotics, or uncontrolled hypertension within the past 30 days
• Concurrent illness likely to interfere with study therapy or to prevent surgical resection
• Pregnant or nursing

Sponsors & Collaborators

• Eastern Cooperative Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (121)

UAB Comprehensive Cancer Center

Birmingham, Alabama, 35294, United States

Location

California Cancer Care, Incorporated - Greenbrae

Greenbrae, California, 94904, United States

Location

Veterans Affairs Medical Center - Palo Alto

Palo Alto, California, 94304, United States

Location

Stanford Cancer Center

Stanford, California, 94305-5824, United States

Location

Aurora Presbyterian Hospital

Aurora, Colorado, 80012, United States

Location

Boulder Community Hospital

Boulder, Colorado, 80301-9019, United States

Location

Penrose Cancer Center at Penrose Hospital

Colorado Springs, Colorado, 80933, United States

Location

St. Anthony Central Hospital

Denver, Colorado, 80204, United States

Location

Porter Adventist Hospital

Denver, Colorado, 80210, United States

Location

Presbyterian - St. Luke's Medical Center

Denver, Colorado, 80218, United States

Location

St. Joseph Hospital

Denver, Colorado, 80218, United States

Location

Rose Medical Center

Denver, Colorado, 80220, United States

Location

CCOP - Colorado Cancer Research Program

Denver, Colorado, 80224-2522, United States

Location

Swedish Medical Center

Englewood, Colorado, 80110, United States

Location

Poudre Valley Hospital

Fort Collins, Colorado, 80524, United States

Location

Front Range Cancer Specialists

Fort Collins, Colorado, 80528, United States

Location

St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center

Grand Junction, Colorado, 81502, United States

Location

North Colorado Medical Center

Greeley, Colorado, 80631, United States

Location

Sky Ridge Medical Center

Lone Tree, Colorado, 80124, United States

Location

Hope Cancer Care Center at Longmont United Hospital

Longmont, Colorado, 80501, United States

Location

McKee Medical Center

Loveland, Colorado, 80539, United States

Location

St. Mary - Corwin Regional Medical Center

Pueblo, Colorado, 81004, United States

Location

North Suburban Medical Center

Thornton, Colorado, 80229, United States

Location

Exempla Lutheran Medical Center

Wheat Ridge, Colorado, 80033, United States

Location

George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus

New Britain, Connecticut, 06050, United States

Location

Tunnell Cancer Center at Beebe Medical Center

Lewes, Delaware, 19958, United States

Location

CCOP - Christiana Care Health Services

Newark, Delaware, 19713, United States

Location

Evanston Hospital

Evanston, Illinois, 60201-1781, United States

Location

Medical Oncology and Hematology Associates - West Des Moines

Clive, Iowa, 50325, United States

Location

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, 50309, United States

Location

John Stoddard Cancer Center at Iowa Methodist Medical Center

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates at John Stoddard Cancer Center

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates at Mercy Cancer Center

Des Moines, Iowa, 50314, United States

Location

Mercy Cancer Center at Mercy Medical Center - Des Moines

Des Moines, Iowa, 50314, United States

Location

John Stoddard Cancer Center at Iowa Lutheran Hospital

Des Moines, Iowa, 50316, United States

Location

Siouxland Hematology-Oncology Associates, LLP

Sioux City, Iowa, 51101, United States

Location

Mercy Medical Center - Sioux City

Sioux City, Iowa, 51104, United States

Location

St. Luke's Regional Medical Center

Sioux City, Iowa, 51104, United States

Location

Cancer Center of Kansas, PA - Chanute

Chanute, Kansas, 66720, United States

Location

Cancer Center of Kansas, PA - Dodge City

Dodge City, Kansas, 67801, United States

Location

Cancer Center of Kansas, PA - El Dorado

El Dorado, Kansas, 67042, United States

Location

Cancer Center of Kansas, PA - Kingman

Kingman, Kansas, 67068, United States

Location

Lawrence Memorial Hospital

Lawrence, Kansas, 66044, United States

Location

Cancer Center of Kansas, PA - Liberal

Liberal, Kansas, 67901, United States

Location

Cancer Center of Kansas, PA - Newton

Newton, Kansas, 67114, United States

Location

Cancer Center of Kansas, PA - Parsons

Parsons, Kansas, 67357, United States

Location

Cancer Center of Kansas, PA - Pratt

Pratt, Kansas, 67124, United States

Location

Cancer Center of Kansas, PA - Salina

Salina, Kansas, 67401, United States

Location

Cancer Center of Kansas, PA - Wellington

Wellington, Kansas, 67152, United States

Location

Associates in Womens Health, PA - North Review

Wichita, Kansas, 67208, United States

Location

Cancer Center of Kansas, PA - Medical Arts Tower

Wichita, Kansas, 67208, United States

Location

Cancer Center of Kansas, PA - Wichita

Wichita, Kansas, 67214, United States

Location

CCOP - Wichita

Wichita, Kansas, 67214, United States

Location

Via Christi Cancer Center at Via Christi Regional Medical Center

Wichita, Kansas, 67214, United States

Location

Cancer Center of Kansas, PA - Winfield

Winfield, Kansas, 67156, United States

Location

Mary Bird Perkins Cancer Center - Baton Rouge

Baton Rouge, Louisiana, 70809, United States

Location

MBCCOP - LSU Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

Medical Center of Louisiana - New Orleans

New Orleans, Louisiana, 70112, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Union Hospital of Cecil County

Elkton, Maryland, 21921, United States

Location

Hickman Cancer Center at Bixby Medical Center

Adrian, Michigan, 49221, United States

Location

Borgess Medical Center

Kalamazoo, Michigan, 49001, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007-3731, United States

Location

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States

Location

Community Cancer Center of Monroe

Monroe, Michigan, 48162, United States

Location

Mercy Memorial Hospital - Monroe

Monroe, Michigan, 48162, United States

Location

Fairview Ridges Hospital

Burnsville, Minnesota, 55337, United States

Location

Mercy and Unity Cancer Center at Mercy Hospital

Coon Rapids, Minnesota, 55433, United States

Location

Fairview Southdale Hospital

Edina, Minnesota, 55435, United States

Location

Fergus Falls Medical Group, PA

Fergus Falls, Minnesota, 56537, United States

Location

Mercy and Unity Cancer Center at Unity Hospital

Fridley, Minnesota, 55432, United States

Location

Hutchinson Area Health Care

Hutchinson, Minnesota, 55350, United States

Location

HealthEast Cancer Care at St. John's Hospital

Maplewood, Minnesota, 55109, United States

Location

Minnesota Oncology Hematology, PA - Maplewood

Maplewood, Minnesota, 55109, United States

Location

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

Minneapolis, Minnesota, 55407, United States

Location

Hennepin County Medical Center - Minneapolis

Minneapolis, Minnesota, 55415, United States

Location

Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center

Robbinsdale, Minnesota, 55422-2900, United States

Location

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, 55416, United States

Location

Park Nicollet Cancer Center

Saint Louis Park, Minnesota, 55416, United States

Location

Regions Hospital Cancer Care Center

Saint Paul, Minnesota, 55101, United States

Location

United Hospital

Saint Paul, Minnesota, 55102, United States

Location

St. Francis Cancer Center at St. Francis Medical Center

Shakopee, Minnesota, 55379, United States

Location

Ridgeview Medical Center

Waconia, Minnesota, 55387, United States

Location

Willmar Cancer Center at Rice Memorial Hospital

Willmar, Minnesota, 56201, United States

Location

Minnesota Oncology Hematology, PA - Woodbury

Woodbury, Minnesota, 55125, United States

Location

Cancer Institute of New Jersey at Cooper - Voorhees

Voorhees Township, New Jersey, 08043, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87131-5636, United States

Location

Stony Brook University Cancer Center

Stony Brook, New York, 11794-9446, United States

Location

CCOP - MeritCare Hospital

Fargo, North Dakota, 58122, United States

Location

Wood County Oncology Center

Bowling Green, Ohio, 43402, United States

Location

North Coast Cancer Care - Clyde

Clyde, Ohio, 43410, United States

Location

Community Cancer Center

Elyria, Ohio, 44035, United States

Location

Hematology Oncology Center

Elyria, Ohio, 44035, United States

Location

Lima Memorial Hospital

Lima, Ohio, 45804, United States

Location

Northwest Ohio Oncology Center

Maumee, Ohio, 43537-1839, United States

Location

Fisher-Titus Medical Center

Norwalk, Ohio, 44857, United States

Location

St. Charles Mercy Hospital

Oregon, Ohio, 43616, United States

Location

Toledo Clinic - Oregon

Oregon, Ohio, 43616, United States

Location

North Coast Cancer Care, Incorporated

Sandusky, Ohio, 44870, United States

Location

Flower Hospital Cancer Center

Sylvania, Ohio, 43560, United States

Location

Mercy Hospital of Tiffin

Tiffin, Ohio, 44883, United States

Location

Toledo Hospital

Toledo, Ohio, 43606, United States

Location

St. Vincent Mercy Medical Center

Toledo, Ohio, 43608, United States

Location

Medical University of Ohio Cancer Center

Toledo, Ohio, 43614, United States

Location

CCOP - Toledo Community Hospital

Toledo, Ohio, 43617, United States

Location

St. Anne Mercy Hospital

Toledo, Ohio, 43623, United States

Location

Toledo Clinic, Incorporated - Main Clinic

Toledo, Ohio, 43623, United States

Location

Fulton County Health Center

Wauseon, Ohio, 43567, United States

Location

Natalie Warren Bryant Cancer Center at St. Francis Hospital

Tulsa, Oklahoma, 74136, United States

Location

Butler Memorial Hospital

Butler, Pennsylvania, 16001, United States

Location

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, 19111-2497, United States

Location

UPMC Cancer Centers

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt-Ingram Cancer Center - Cool Springs

Franklin, Tennessee, 37067, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

Fredericksburg Oncology, Incorporated

Fredericksburg, Virginia, 22401, United States

Location

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, 54307-3508, United States

Location

Holy Family Memorial Medical Center Cancer Care Center

Manitowoc, Wisconsin, 54221-1450, United States

Location

Bay Area Cancer Care Center at Bay Area Medical Center

Marinette, Wisconsin, 54143, United States

Location

Regional Cancer Center at Oconomowoc Memorial Hospital

Oconomowoc, Wisconsin, 53066, United States

Location

St. Nicholas Hospital

Sheboygan, Wisconsin, 53081, United States

Location

Waukesha Memorial Hospital Regional Cancer Center

Waukesha, Wisconsin, 53188, United States

Location

Related Publications (2)

• Marur S, Li S, Cmelak AJ, Gillison ML, Zhao WJ, Ferris RL, Westra WH, Gilbert J, Bauman JE, Wagner LI, Trevarthen DR, Balkrishna J, Murphy BA, Agrawal N, Colevas AD, Chung CH, Burtness B. E1308: Phase II Trial of Induction Chemotherapy Followed by Reduced-Dose Radiation and Weekly Cetuximab in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx- ECOG-ACRIN Cancer Research Group. J Clin Oncol. 2017 Feb 10;35(5):490-497. doi: 10.1200/JCO.2016.68.3300. Epub 2016 Dec 28.

  PMID: 28029303 RESULT

• Psyrri A, Rampias T, Vermorken JB. The current and future impact of human papillomavirus on treatment of squamous cell carcinoma of the head and neck. Ann Oncol. 2014 Nov;25(11):2101-2115. doi: 10.1093/annonc/mdu265. Epub 2014 Jul 23.

  PMID: 25057165 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms; Precancerous Conditions; Papillomavirus Infections; Squamous Cell Carcinoma of Head and Neck; Tongue Neoplasms

Interventions

Cetuximab; Radiotherapy, Intensity-Modulated; Paclitaxel; Albumin-Bound Paclitaxel; Cisplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Mouth Neoplasms; Mouth Diseases; Stomatognathic Diseases; Tongue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: ECOG-ACRIN statistician
• Organization: ECOG-ACRIN Statistical Office

617-632-3012

Study Officials

• Shanthi Marur, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2010
• First Posted: March 10, 2010
• Study Start: August 11, 2010
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: June 28, 2023
• Results First Posted: October 28, 2015

Record last verified: 2023-06

Locations

US (121)