Cetuximab, Cisplatin, Fluorouracil, and Radiation Therapy in Treating Patients With Anal Cancer

Anal Cancer Clinical Trial

Official title:

Phase II Trial of Cetuximab Plus Cisplatin, 5- Fluorouracil and Radiation in Immunocompetent Patients With Anal Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00316888
• Other study ID #: E3205
• Secondary ID: E3205U10CA023318
• Status: Completed
• Phase: Phase 2
• Start date: February 28, 2007
• Est. completion date: August 17, 2021

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: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as cisplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Cetuximab may help cisplatin and fluorouracil work better by making tumor cells more sensitive to the drugs. It may also make tumor cells more sensitive to radiation therapy. Giving cetuximab together with chemotherapy and radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cetuximab together with cisplatin, fluorouracil, and radiation therapy works in treating immunocompetent patients with stage I (closed to accrual as of 11/3/2008), stage II, (some stage II closed to accrual as of 11/3/2008) or stage III anal cancer.

Description:

OBJECTIVES:

Primary Objective:

• Determine whether the addition of cetuximab to combined modality therapy (CMT) comprising cisplatin, fluorouracil, and radiotherapy reduces the local failure rate by ≥ 50% at 3 years (compared with historical data) in immunocompetent patients with stage I-III invasive anal carcinoma.

Secondary Objectives:

• Determine objective response rate (complete and partial), progression-free survival, colostomy-free survival, and overall survival.

• Determine the overall toxicity of concurrent cisplatin, fluorouracil, and radiation therapy combined with cetuximab.

Exploratory Objectives:

• Evaluate the effect of cetuximab and CMT on anogenital herpes papilloma virus (HPV) infection and anal cytology.

• Evaluate whether moderate to strong expression of epidermal growth factor receptor, Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and P-Akt (as determined by immunohistochemistry) is associated with an increased risk of local failure.

OUTLINE: This is a multicenter study with two sequential arms. Arm I was closed to accrual as of 11/3/2008, and arm II opened to accrual on 8/18/2009. Patients are assigned to 1 of the 2 treatment arms.

• Arm I (closed to accrual as of 11/3/2008): Patients receive cisplatin intravenously (IV) over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57.

• Arm II (open to accrual on 8/18/2009): Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 8 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8.

After completion of study treatment, patients are followed periodically for up to 10 years.

PROJECTED ACCRUAL: A total of 62 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: August 17, 2021
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

INCLUSION CRITERIA:

• Histologically confirmed anal canal or perianal (anal margin) squamous cell carcinoma

• Stage I-IIIB (closed to accrual as of 11/3/2008)

• Stage II (T3, N0 only), IIIA, or IIIB

• Tumors of nonkeratinizing histology, such as basaloid, transitional cell, or cloacogenic histology, allowed

• No well-differentiated stage I anal margin cancer

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Hemoglobin = 10 g/dL

• Platelet count = 100,000/mm^3

• Absolute neutrophil count > 1,500/mm^3

• Creatinine = 1.5 times upper limit of normal (ULN) OR creatinine clearance > 60 mL/min

• Bilirubin = 2 times ULN

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times ULN

• Negative pregnancy test

• Fertile patients must use effective contraception during and for = 3 months after completion of study treatment

• No other malignancies except nonmelanomatous skin cancer

• Prior malignancies must be in remission for = 5 years

• Patients with a known risk factor for human immunodeficiency virus (HIV) infection must undergo HIV testing within 90 days before study entry AND must be HIV negative by antibody detection, culture, or quantitative assay of plasma HIV ribonucleic acid (RNA)

EXCLUSION CRITERIA:

• Presence of the following conditions within the past 6 months:

• Active infection

• Uncontrolled diabetes

• New York Heart Association class II-IV congestive heart failure

• Cerebrovascular accident

• Transient ischemic attack

• Uncontrolled hypertension

• Unstable angina

• Myocardial infarction

• History of rheumatic disorders, irritable bowel syndrome, or inflammatory bowel disease

• Known HIV positivity

• Known risk factors for HIV infection

• Prior radiotherapy or chemotherapy for this malignancy

• Prior pelvic radiotherapy

• Prior potentially curative surgery (i.e., abdominal or peritoneal resection) for anal cancer

• Pregnant or nursing

Related Conditions & MeSH terms

• Anal Cancer
• Anus Neoplasms

Intervention

Biological:
• cetuximab
Given IV

Drug:
• cisplatin
Given IV
• fluorouracil
Given IV

Radiation:
• radiotherapy
Given once daily 5 days a week for 5 weeks

Locations

Country	Name	City	State
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	Greater Baltimore Medical Center Cancer Center	Baltimore	Maryland
United States	Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	Louisiana
United States	Wood County Oncology Center	Bowling Green	Ohio
United States	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Hematology and Oncology Associates	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Marshfield Clinic - Chippewa Center	Chippewa Falls	Wisconsin
United States	CCOP - Columbus	Columbus	Ohio
United States	Doctors Hospital at Ohio Health	Columbus	Ohio
United States	Grant Medical Center Cancer Care	Columbus	Ohio
United States	Mount Carmel Health - West Hospital	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	Marshfield Clinic Cancer Care at Regional Cancer Center	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Community Cancer Center	Elyria	Ohio
United States	Hematology Oncology Center	Elyria	Ohio
United States	Front Range Cancer Specialists	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Kellogg Cancer Care Center	Highland Park	Illinois
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	William N. Wishard Memorial Hospital	Indianapolis	Indiana
United States	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Provena St. Mary's Regional Cancer Center - Kankakee	Kankakee	Illinois
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas
United States	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois
United States	Lima Memorial Hospital	Lima	Ohio
United States	Cancer Resource Center - Lincoln	Lincoln	Nebraska
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology - Maplewood	Maplewood	Minnesota
United States	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio
United States	Marshfield Clinic - Marshfield Center	Marshfield	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	Marshfield Clinic - Lakeland Center	Minocqua	Wisconsin
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital - Monroe	Monroe	Michigan
United States	Carol G. Simon Cancer Center at Morristown Memorial Hospital	Morristown	New Jersey
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	Medical Center of Louisiana - New Orleans	New Orleans	Louisiana
United States	NYU Cancer Institute at New York University Medical Center	New York	New York
United States	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Cancer Care and Hematology Specialists of Chicagoland - Niles	Niles	Illinois
United States	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Immanuel Medical Center	Omaha	Nebraska
United States	Lakeside Hospital	Omaha	Nebraska
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Toledo Clinic - Oregon	Oregon	Ohio
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania
United States	Joan Karnell Cancer Center at Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Southern Ohio Medical Center Cancer Center	Portsmouth	Ohio
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Ministry Medical Group at Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin
United States	Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Swedish-American Regional Cancer Center	Rockford	Illinois
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	Hematology and Oncology Associates of Northeastern Pennsylvania	Scranton	Pennsylvania
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
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	Hematology Oncology Associates - Skokie	Skokie	Illinois
United States	Community Hospital of Springfield and Clark County	Springfield	Ohio
United States	Stanford Cancer Center	Stanford	California
United States	Marshfield Clinic at Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Overlook Hospital	Summit	New Jersey
United States	Flower Hospital Cancer Center	Sylvania	Ohio
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	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Marshfield Clinic - Wausau Center	Wausau	Wisconsin
United States	Fulton County Health Center	Wauseon	Ohio
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Marshfield Clinic - Weston Center	Weston	Wisconsin
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	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology - Woodbury	Woodbury	Minnesota
United States	Genesis - Good Samaritan Hospital	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
ECOG-ACRIN Cancer Research Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Garg M, Lee JY, Kachnic LA, et al.: Phase II trials of cetuximab (CX) plus cisplatin (CDDP), 5-fluorouracil (5-FU) and radiation (RT) in immunocompetent (ECOG 3205) and HIV-positive (AMC045) patients with squamous cell carcinoma of the anal canal (SCAC): safety and preliminary efficacy results. [Abstract] J Clin Oncol 30 (Suppl 15): A-4030, 2012.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Local Failure Rate at 3 Years	Local failure was defined as progression/relapse of disease in the anal canal and/or regional organs and/or regional lymph nodes after completion of protocol therapy, or progression during protocol therapy. Lost to follow-up and death (regardless of cause of death) prior to 3 years were also considered as local failures. For the calculation of local failure rate at 3 years, patients were classified into two groups (ie, coded as binary variable): failure (patients with local failure events prior to 3 years) vs. no failure (patients who still alive and had no local failure at 3 years). The binomial proportion and its exact two-sided 80% confidence interval (CI) were used to estimate it.	assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3
Secondary	3-year Overall Survival Rate	Overall survival (OS) is defined as time from registration to death from any cause. Patients alive are censored at the last contact date. Kaplan-Meier method was used to estimate the 3-year OS rate.	assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3
Secondary	3-year Progression-free Survival Rate	Progression-free survival (PFS) was defined as time from registration to disease progression, relapse or death (whichever occurred first), censoring cases without PFS events at the date of last disease assessment documenting the patient was free of progression/relapse. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Kaplan-Meier method was used to estimate the 3-year PFS rate.	assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3
Secondary	Objective Response Rate	Objective response rate is defined as number of patients with complete response (CR) or partial response (PR) divided by all eligible and treated patients. Responses are evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline. CR is defined as disappearance of all target and non-target lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameters), and/or persistence of one or more non-target lesion(s).	Tumor assessments were made at baseline, within 4 weeks of the completion of protocol treatment, then every 6 months if patient was 1-4 years from registration, yearly if patient was 5-10 years from registration until progression/relapse using the RECIST
Secondary	3-year Colostomy-free Survival Rate	Colostomy-free survival was defined as time from registration until time of colostomy or death without colostomy, censoring cases without colostomy at the data of last disease assessment documenting the patient was free of colostomy. Kaplan-Meier method was used to estimate the 3-year colostomy-free survival rate.	assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3