Cetuximab, Cisplatin, Fluorouracil, and Radiation Therapy in Treating Patients With Anal Cancer
- Conditions
- Anal Cancer
- Interventions
- Registration Number
- NCT00316888
- Lead Sponsor
- ECOG-ACRIN Cancer Research Group
- Brief 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.
- Detailed 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 & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 63
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm II (open to accrual on 8/18/2009) radiotherapy 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 1 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. Treatment continues in the absence of disease progression or unacceptable toxicity. Arm I (closed to accrual as of 11/3/2008) cisplatin Patients receive cisplatin 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. Treatment continues in the absence of disease progression or unacceptable toxicity. Arm I (closed to accrual as of 11/3/2008) cetuximab Patients receive cisplatin 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. Treatment continues in the absence of disease progression or unacceptable toxicity. Arm I (closed to accrual as of 11/3/2008) radiotherapy Patients receive cisplatin 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. Treatment continues in the absence of disease progression or unacceptable toxicity. Arm II (open to accrual on 8/18/2009) cetuximab 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 1 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. Treatment continues in the absence of disease progression or unacceptable toxicity. Arm I (closed to accrual as of 11/3/2008) fluorouracil Patients receive cisplatin 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. Treatment continues in the absence of disease progression or unacceptable toxicity. Arm II (open to accrual on 8/18/2009) cisplatin 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 1 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. Treatment continues in the absence of disease progression or unacceptable toxicity. Arm II (open to accrual on 8/18/2009) fluorouracil 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 1 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. Treatment continues in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Local Failure Rate at 3 Years assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3 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.
- Secondary Outcome Measures
Name Time Method Objective Response Rate 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 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).
3-year Progression-free Survival Rate assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3 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.
3-year Overall Survival Rate assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3 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.
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 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.
Trial Locations
- Locations (125)
Borgess Medical Center
🇺🇸Kalamazoo, Michigan, United States
Decatur Memorial Hospital Cancer Care Institute
🇺🇸Decatur, Illinois, United States
Greater Baltimore Medical Center Cancer Center
🇺🇸Baltimore, Maryland, United States
Minnesota Oncology - Woodbury
🇺🇸Woodbury, Minnesota, United States
Licking Memorial Cancer Care Program at Licking Memorial Hospital
🇺🇸Newark, Ohio, United States
Park Nicollet Cancer Center
🇺🇸Saint Louis Park, Minnesota, United States
Marshfield Clinic - Weston Center
🇺🇸Weston, Wisconsin, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Marshfield Clinic at Saint Michael's Hospital
🇺🇸Stevens Point, Wisconsin, United States
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
🇺🇸Chicago, Illinois, United States
Riverside Methodist Hospital Cancer Care
🇺🇸Columbus, Ohio, United States
Marshfield Clinic - Wausau Center
🇺🇸Wausau, Wisconsin, United States
CCOP - Columbus
🇺🇸Columbus, Ohio, United States
Indiana University Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
William N. Wishard Memorial Hospital
🇺🇸Indianapolis, Indiana, United States
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Cancer Center of Kansas, PA - Pratt
🇺🇸Pratt, Kansas, United States
Cancer Center of Kansas, PA - Winfield
🇺🇸Winfield, Kansas, United States
Cancer Center of Kansas - Fort Scott
🇺🇸Fort Scott, Kansas, United States
Cancer Center of Kansas, PA - Dodge City
🇺🇸Dodge City, Kansas, United States
Mercy and Unity Cancer Center at Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Lakeview Hospital
🇺🇸Stillwater, Minnesota, United States
Cancer Center of Kansas, PA - Salina
🇺🇸Salina, Kansas, United States
Mercy and Unity Cancer Center at Unity Hospital
🇺🇸Fridley, Minnesota, United States
CCOP - Wichita
🇺🇸Wichita, Kansas, United States
Poudre Valley Hospital
🇺🇸Fort Collins, Colorado, United States
Cancer Center of Kansas, PA - Kingman
🇺🇸Kingman, Kansas, United States
Lawrence Memorial Hospital
🇺🇸Lawrence, Kansas, United States
Cancer Center of Kansas, PA - Liberal
🇺🇸Liberal, Kansas, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Humphrey Cancer Center at North Memorial Outpatient Center
🇺🇸Robbinsdale, Minnesota, United States
Regions Hospital Cancer Care Center
🇺🇸Saint Paul, Minnesota, United States
Cancer Center of Kansas, PA - Wichita
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas, PA - El Dorado
🇺🇸El Dorado, Kansas, United States
Cancer Center of Kansas, PA - Wellington
🇺🇸Wellington, Kansas, United States
HealthEast Cancer Care at St. John's Hospital
🇺🇸Maplewood, Minnesota, United States
CCOP - Metro-Minnesota
🇺🇸Saint Louis Park, Minnesota, United States
Minnesota Oncology - Maplewood
🇺🇸Maplewood, Minnesota, United States
Hutchinson Area Health Care
🇺🇸Hutchinson, Minnesota, United States
Willmar Cancer Center at Rice Memorial Hospital
🇺🇸Willmar, Minnesota, United States
Alegant Health Cancer Center at Bergan Mercy Medical Center
🇺🇸Omaha, Nebraska, United States
Creighton University Medical Center
🇺🇸Omaha, Nebraska, United States
CCOP - Missouri Valley Cancer Consortium
🇺🇸Omaha, Nebraska, United States
Lakeside Hospital
🇺🇸Omaha, Nebraska, United States
Immanuel Medical Center
🇺🇸Omaha, Nebraska, United States
Stanford Cancer Center
🇺🇸Stanford, California, United States
Front Range Cancer Specialists
🇺🇸Fort Collins, Colorado, United States
Kellogg Cancer Care Center
🇺🇸Highland Park, Illinois, United States
Hematology and Oncology Associates
🇺🇸Chicago, Illinois, United States
Cancer Care and Hematology Specialists of Chicagoland - Niles
🇺🇸Niles, Illinois, United States
Swedish-American Regional Cancer Center
🇺🇸Rockford, Illinois, United States
Provena St. Mary's Regional Cancer Center - Kankakee
🇺🇸Kankakee, Illinois, United States
North Shore Oncology and Hematology Associates, Limited - Libertyville
🇺🇸Libertyville, Illinois, United States
Hematology Oncology Associates - Skokie
🇺🇸Skokie, Illinois, United States
CCOP - Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Cedar Rapids Oncology Associates
🇺🇸Cedar Rapids, Iowa, United States
Mercy Regional Cancer Center at Mercy Medical Center
🇺🇸Cedar Rapids, Iowa, United States
Siouxland Hematology-Oncology Associates, LLP
🇺🇸Sioux City, Iowa, United States
Mercy Medical Center - Sioux City
🇺🇸Sioux City, Iowa, United States
St. Luke's Regional Medical Center
🇺🇸Sioux City, Iowa, United States
Cancer Center of Kansas, PA - Chanute
🇺🇸Chanute, Kansas, United States
Cancer Center of Kansas-Independence
🇺🇸Independence, Kansas, United States
Cancer Center of Kansas, PA - Newton
🇺🇸Newton, Kansas, United States
Cancer Center of Kansas, PA - Parsons
🇺🇸Parsons, Kansas, 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
Via Christi Cancer Center at Via Christi Regional Medical Center
🇺🇸Wichita, Kansas, United States
Mary Bird Perkins Cancer Center - Baton Rouge
🇺🇸Baton Rouge, Louisiana, United States
MBCCOP - LSU Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
Medical Center of Louisiana - New Orleans
🇺🇸New Orleans, Louisiana, United States
Hickman Cancer Center at Bixby Medical Center
🇺🇸Adrian, Michigan, United States
Community Cancer Center of Monroe
🇺🇸Monroe, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Mercy Memorial Hospital - Monroe
🇺🇸Monroe, Michigan, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
Hennepin County Medical Center - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
St. Francis Cancer Center at St. Francis Medical Center
🇺🇸Shakopee, Minnesota, United States
Cancer Resource Center - Lincoln
🇺🇸Lincoln, Nebraska, United States
Albert Einstein Cancer Center at Albert Einstein College of Medicine
🇺🇸Bronx, New York, United States
Overlook Hospital
🇺🇸Summit, New Jersey, United States
Carol G. Simon Cancer Center at Morristown Memorial Hospital
🇺🇸Morristown, New Jersey, United States
Wood County Oncology Center
🇺🇸Bowling Green, Ohio, United States
Adena Regional Medical Center
🇺🇸Chillicothe, Ohio, United States
NYU Cancer Institute at New York University Medical Center
🇺🇸New York, New York, United States
Doctors Hospital at Ohio Health
🇺🇸Columbus, Ohio, United States
Community Cancer Center
🇺🇸Elyria, Ohio, United States
Grant Medical Center Cancer Care
🇺🇸Columbus, Ohio, United States
Grady Memorial Hospital
🇺🇸Delaware, Ohio, United States
Mount Carmel Health - West Hospital
🇺🇸Columbus, Ohio, United States
Hematology Oncology Center
🇺🇸Elyria, Ohio, United States
Northwest Ohio Oncology Center
🇺🇸Maumee, Ohio, United States
Strecker Cancer Center at Marietta Memorial Hospital
🇺🇸Marietta, Ohio, United States
Fairfield Medical Center
🇺🇸Lancaster, Ohio, United States
Lima Memorial Hospital
🇺🇸Lima, Ohio, United States
Knox Community Hospital
🇺🇸Mount Vernon, Ohio, United States
St. Charles Mercy Hospital
🇺🇸Oregon, Ohio, United States
Toledo Clinic - Oregon
🇺🇸Oregon, Ohio, United States
Community Hospital of Springfield and Clark County
🇺🇸Springfield, Ohio, United States
Southern Ohio Medical Center Cancer Center
🇺🇸Portsmouth, Ohio, United States
Flower Hospital Cancer Center
🇺🇸Sylvania, Ohio, United States
Mercy Hospital of Tiffin
🇺🇸Tiffin, Ohio, United States
St. Vincent Mercy Medical Center
🇺🇸Toledo, Ohio, United States
Toledo Hospital
🇺🇸Toledo, Ohio, United States
Medical University of Ohio Cancer Center
🇺🇸Toledo, Ohio, United States
St. Anne Mercy Hospital
🇺🇸Toledo, Ohio, United States
CCOP - Toledo Community Hospital
🇺🇸Toledo, Ohio, United States
Toledo Clinic, Incorporated - Main Clinic
🇺🇸Toledo, Ohio, United States
Fulton County Health Center
🇺🇸Wauseon, Ohio, United States
Genesis - Good Samaritan Hospital
🇺🇸Zanesville, Ohio, United States
Fox Chase Cancer Center - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Joan Karnell Cancer Center at Pennsylvania Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Fredericksburg Oncology, Incorporated
🇺🇸Fredericksburg, Virginia, United States
University of Virginia Cancer Center
🇺🇸Charlottesville, Virginia, United States
Hematology and Oncology Associates of Northeastern Pennsylvania
🇺🇸Scranton, Pennsylvania, United States
Marshfield Clinic - Chippewa Center
🇺🇸Chippewa Falls, Wisconsin, United States
UW Cancer Center Johnson Creek
🇺🇸Johnson Creek, Wisconsin, United States
Marshfield Clinic Cancer Care at Regional Cancer Center
🇺🇸Eau Claire, Wisconsin, United States
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
🇺🇸Madison, Wisconsin, United States
Marshfield Clinic - Marshfield Center
🇺🇸Marshfield, Wisconsin, United States
Marshfield Clinic - Indianhead Center
🇺🇸Rice Lake, Wisconsin, United States
Marshfield Clinic - Wisconsin Rapids Center
🇺🇸Wisconsin Rapids, Wisconsin, United States
Marshfield Clinic - Lakeland Center
🇺🇸Minocqua, Wisconsin, United States
Ministry Medical Group at Saint Mary's Hospital
🇺🇸Rhinelander, Wisconsin, United States