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

Head and Neck Cancer Clinical Trial

Official title:

A Phase II Trial of Induction Chemotherapy Followed by Cetuximab (Erbitux) With Low Dose vs. Standard Dose IMRT in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01084083
• Other study ID #: CDR0000665170
• Secondary ID: ECOG-E1308U10CA0
• Status: Completed
• Phase: Phase 2
• Start date: August 11, 2010
• Est. completion date: January 2015

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

OBJECTIVES:

Primary

• To evaluate the efficacy of induction therapy comprising paclitaxel, cisplatin, and cetuximab followed by cetuximab in combination with low-dose or standard-dose intensity-modulated radiotherapy, as measured by 2-year progression-free survival (PFS), in patients with human papillomavirus(HPV)-associated resectable stage III-IVB squamous cell carcinoma of the oropharynx.

Secondary

• To assess overall survival.

• To evaluate the objective response, local control, and metastatic rate.

• To evaluate early and late toxicities of treatment.

Tertiary

• To evaluate quality of life and speech and swallowing function as measured by Functional Assessment of Cancer Therapy - General (FACT-G), Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN), and Vanderbilt Head and Neck Symptom Survey (VHNSS).

• To assess the effect of treatment-induced fatigue on general physical functioning in patients with head and neck cancer.

• To correlate functional decline with clinical, physical, and biologic correlatives.

• To evaluate radiation-resistance markers, including ERCC1 single nucleotide polymorphism and protein expression, and to correlate them with treatment efficacy.

• To demonstrate the usefulness of biomarkers, including ERCC1, epidermal growth factor receptor (EGFR), cytokine and chemokine markers, and plasma transforming growth factor alpha (TGFA) and transforming growth factor beta (TGFB) levels, in predicting progression-free survival (PFS) and other outcome parameters.

• To evaluate the correlation between the efficacy of cetuximab and polymorphisms in FcγR-receptors.

• To evaluate functional outcome and biological parameters, including telomere length, angiotensin-converting enzyme polymorphism, and C-reactive protein level.

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive cisplatin intravenously (IV) over 1 hour on day 1 and paclitaxel IV over 3 hours and cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for 3 courses. Patients then undergo evaluation of response to induction therapy. Patients with a clinical complete response (CR) at the primary tumor site proceed to group 1 of concurrent radiotherapy and cetuximab. Patients with a clinical partial response (PR) or stable disease (SD) at the primary tumor site or those with grossly positive disease at the primary tumor site proceed to group 2 of concurrent radiotherapy and cetuximab.

• Concurrent radiotherapy and cetuximab: Treatment begins 14-21 days after the last day of induction therapy.

• Group 1 (CR): 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.

• Group 2 (PR, SD, or grossly positive disease): 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.

Patients complete questionnaires assessing fatigue, physical function, weight loss, quality of life, head and neck symptom burden, and speech and swallowing function at baseline and at 1, 6, 12, and 24 months after completion of study treatment.

Tumor tissue and serum samples may be collected periodically for correlative laboratory studies.

After completion of study treatment, patients are followed up periodically for 3 years.

PROJECTED ACCRUAL: 83 patients

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

• Creatinine clearance = 60 mL/min

• Negative pregnancy test

• Fertile patients must use effective contraception

• No history of another malignancy (except for carcinoma in situ of the cervix and/or nonmelanomatous skin cancer) unless it has been curatively treated and the patient has been disease-free for = 2 years

• Patients with any of the following within the past 6 months are eligible provided they have been evaluated by a cardiologist and/or neurologist before study entry:

• New York Heart Association (NYHA) class III-IV congestive heart failure

• Cerebrovascular accident or transient ischemic attack

• Unstable angina

• Myocardial infarction (with or without ST elevation)

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Head and Neck Cancer
• Precancerous Condition
• Precancerous Conditions

Intervention

Biological:
• cetuximab
Given IV

Radiation:
• intensity-modulated radiation therapy (IMRT)
Patients undergo low-dose OR standard dose IMRT based on their clinical response to induction therapy

Drug:
• Paclitaxel
Given IV, 90 mg/m^2 on days 1, 8 and 15
• Cisplatin
Given IV, 75 mg/m^2 on day 1

Locations

Country	Name	City	State
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Aurora Presbyterian Hospital	Aurora	Colorado
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	Louisiana
United States	UAB Comprehensive Cancer Center	Birmingham	Alabama
United States	Boulder Community Hospital	Boulder	Colorado
United States	Wood County Oncology Center	Bowling Green	Ohio
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Butler Memorial Hospital	Butler	Pennsylvania
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa
United States	North Coast Cancer Care - Clyde	Clyde	Ohio
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	CCOP - Colorado Cancer Research Program	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - St. Luke's Medical Center	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	St. Anthony Central Hospital	Denver	Colorado
United States	St. Joseph Hospital	Denver	Colorado
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	Community Cancer Center	Elyria	Ohio
United States	Hematology Oncology Center	Elyria	Ohio
United States	Swedish Medical Center	Englewood	Colorado
United States	Evanston Hospital	Evanston	Illinois
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	Fergus Falls Medical Group, PA	Fergus Falls	Minnesota
United States	Front Range Cancer Specialists	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Vanderbilt-Ingram Cancer Center - Cool Springs	Franklin	Tennessee
United States	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado
United States	North Colorado Medical Center	Greeley	Colorado
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	California Cancer Care, Incorporated - Greenbrae	Greenbrae	California
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware
United States	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas
United States	Lima Memorial Hospital	Lima	Ohio
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado
United States	McKee Medical Center	Loveland	Colorado
United States	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital - Monroe	Monroe	Michigan
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus	New Britain	Connecticut
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	Medical Center of Louisiana - New Orleans	New Orleans	Louisiana
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Fisher-Titus Medical Center	Norwalk	Ohio
United States	Regional Cancer Center at Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Toledo Clinic - Oregon	Oregon	Ohio
United States	Veterans Affairs Medical Center - Palo Alto	Palo Alto	California
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania
United States	UPMC Cancer Centers	Pittsburgh	Pennsylvania
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado
United States	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	Regions Hospital Cancer Care Center	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	North Coast Cancer Care, Incorporated	Sandusky	Ohio
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	St. Nicholas Hospital	Sheboygan	Wisconsin
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Stanford Cancer Center	Stanford	California
United States	Stony Brook University Cancer Center	Stony Brook	New York
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	North Suburban Medical Center	Thornton	Colorado
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	St. Anne Mercy Hospital	Toledo	Ohio
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio
United States	Toledo Hospital	Toledo	Ohio
United States	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Waukesha Memorial Hospital Regional Cancer Center	Waukesha	Wisconsin
United States	Fulton County Health Center	Wauseon	Ohio
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	24-months Overall Survival	OS was defined as the time from registration to death, or censored at last date known alive. Kaplan-Meier method was used to estimate the overall survival rate at 24 months.	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	Primary Clinical Response Rate	Primary clinical response rate is defined as the proportion of patients with complete response or partial response at their primary sites after induction therapy. Response status for the primary site was classified by clinical examination using endoscopy. If, however, the clinical response status of the primary was unclear based on endoscopy, then the CT or MRI (required at the end of induction) was used to determine status of the primary. If clinical and radiological evaluation of the primary was unclear, a biopsy was considered at the discretion of the treating physician.	assessed within 14 days after delivery of the third cycle of induction therapy