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

NCT ID: NCT00316888

Last Updated: 2023-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-02-28
• Study Completion Date: 2021-08-17

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.

Conditions

Anal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I (closed to accrual as of 11/3/2008)

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.

Group Type: EXPERIMENTAL

cetuximab

Intervention Type: BIOLOGICAL

Given IV

cisplatin

Intervention Type: DRUG

Given IV

fluorouracil

Intervention Type: DRUG

Given IV

radiotherapy

Intervention Type: RADIATION

Given once daily 5 days a week for 5 weeks

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 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.

Group Type: EXPERIMENTAL

cetuximab

Intervention Type: BIOLOGICAL

Given IV

cisplatin

Intervention Type: DRUG

Given IV

fluorouracil

Intervention Type: DRUG

Given IV

radiotherapy

Intervention Type: RADIATION

Given once daily 5 days a week for 5 weeks

Interventions

cetuximab

Given IV

Intervention Type: BIOLOGICAL

cisplatin

Given IV

Intervention Type: DRUG

fluorouracil

Given IV

Intervention Type: DRUG

radiotherapy

Given once daily 5 days a week for 5 weeks

Intervention Type: RADIATION

Other Intervention Names

Erbitux; Cis-diaminedichloroplatinum Cis-diaminedichloroplatinum (II); Platinol; Platinol-AQ; cis-platinum; diaminedichloroplatinum; DDP; 5-Fluorouracil; 5-FU; Adrucil; Efudex; radiation therapy

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

ECOG-ACRIN Cancer Research Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Madhur K. Garg, MD

Role: STUDY_CHAIR

Montefiore Medical Center

Joseph A. Sparano, MD

Role: STUDY_CHAIR

Montefiore Medical Center

Locations

Stanford Cancer Center

Stanford, California, United States

Poudre Valley Hospital

Fort Collins, Colorado, United States

Front Range Cancer Specialists

Fort Collins, Colorado, United States

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

Hematology and Oncology Associates

Chicago, Illinois, United States

Decatur Memorial Hospital Cancer Care Institute

Decatur, Illinois, United States

Kellogg Cancer Care Center

Highland Park, 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

Cancer Care and Hematology Specialists of Chicagoland - Niles

Niles, Illinois, United States

Swedish-American Regional Cancer Center

Rockford, Illinois, United States

Hematology Oncology Associates - Skokie

Skokie, Illinois, United States

CCOP - Carle Cancer Center

Urbana, Illinois, United States

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

William N. Wishard Memorial Hospital

Indianapolis, Indiana, 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, PA - Dodge City

Dodge City, Kansas, United States

Cancer Center of Kansas, PA - El Dorado

El Dorado, Kansas, United States

Cancer Center of Kansas - Fort Scott

Fort Scott, Kansas, United States

Cancer Center of Kansas-Independence

Independence, Kansas, 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

Cancer Center of Kansas, PA - Newton

Newton, Kansas, United States

Cancer Center of Kansas, PA - Parsons

Parsons, Kansas, United States

Cancer Center of Kansas, PA - Pratt

Pratt, Kansas, United States

Cancer Center of Kansas, PA - Salina

Salina, Kansas, United States

Cancer Center of Kansas, PA - Wellington

Wellington, 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

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

Cancer Center of Kansas, PA - Winfield

Winfield, 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

Greater Baltimore Medical Center Cancer Center

Baltimore, Maryland, United States

Hickman Cancer Center at Bixby Medical Center

Adrian, Michigan, United States

Borgess Medical Center

Kalamazoo, Michigan, United States

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

Community Cancer Center of Monroe

Monroe, Michigan, United States

Mercy Memorial Hospital - Monroe

Monroe, Michigan, United States

Fairview Ridges Hospital

Burnsville, Minnesota, United States

Mercy and Unity Cancer Center at Mercy Hospital

Coon Rapids, Minnesota, United States

Fairview Southdale Hospital

Edina, Minnesota, United States

Mercy and Unity Cancer Center at Unity Hospital

Fridley, Minnesota, United States

Hutchinson Area Health Care

Hutchinson, Minnesota, United States

HealthEast Cancer Care at St. John's Hospital

Maplewood, Minnesota, United States

Minnesota Oncology - Maplewood

Maplewood, Minnesota, United States

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

Minneapolis, Minnesota, United States

Hennepin County Medical Center - Minneapolis

Minneapolis, Minnesota, United States

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

St. Francis Cancer Center at St. Francis Medical Center

Shakopee, Minnesota, United States

Lakeview Hospital

Stillwater, Minnesota, United States

Ridgeview Medical Center

Waconia, Minnesota, United States

Willmar Cancer Center at Rice Memorial Hospital

Willmar, Minnesota, United States

Minnesota Oncology - Woodbury

Woodbury, Minnesota, United States

Cancer Resource Center - Lincoln

Lincoln, Nebraska, United States

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, United States

Immanuel Medical Center

Omaha, Nebraska, United States

Alegant Health Cancer Center at Bergan Mercy Medical Center

Omaha, Nebraska, United States

Lakeside Hospital

Omaha, Nebraska, United States

Creighton University Medical Center

Omaha, Nebraska, United States

Carol G. Simon Cancer Center at Morristown Memorial Hospital

Morristown, New Jersey, United States

Overlook Hospital

Summit, New Jersey, United States

NYU Cancer Institute at New York University Medical Center

New York, New York, United States

Albert Einstein Cancer Center at Albert Einstein College of Medicine

The Bronx, New York, United States

Wood County Oncology Center

Bowling Green, Ohio, United States

Adena Regional Medical Center

Chillicothe, Ohio, United States

Riverside Methodist Hospital Cancer Care

Columbus, Ohio, United States

CCOP - Columbus

Columbus, Ohio, United States

Grant Medical Center Cancer Care

Columbus, Ohio, United States

Mount Carmel Health - West Hospital

Columbus, Ohio, United States

Doctors Hospital at Ohio Health

Columbus, Ohio, United States

Grady Memorial Hospital

Delaware, Ohio, United States

Community Cancer Center

Elyria, Ohio, United States

Hematology Oncology Center

Elyria, Ohio, United States

Fairfield Medical Center

Lancaster, Ohio, United States

Lima Memorial Hospital

Lima, Ohio, United States

Strecker Cancer Center at Marietta Memorial Hospital

Marietta, Ohio, United States

Northwest Ohio Oncology Center

Maumee, Ohio, United States

Knox Community Hospital

Mount Vernon, Ohio, United States

Licking Memorial Cancer Care Program at Licking Memorial Hospital

Newark, Ohio, United States

St. Charles Mercy Hospital

Oregon, Ohio, United States

Toledo Clinic - Oregon

Oregon, Ohio, United States

Southern Ohio Medical Center Cancer Center

Portsmouth, Ohio, United States

Community Hospital of Springfield and Clark County

Springfield, Ohio, United States

Flower Hospital Cancer Center

Sylvania, Ohio, United States

Mercy Hospital of Tiffin

Tiffin, Ohio, United States

Toledo Hospital

Toledo, Ohio, United States

St. Vincent Mercy Medical Center

Toledo, Ohio, United States

Medical University of Ohio Cancer Center

Toledo, Ohio, United States

CCOP - Toledo Community Hospital

Toledo, Ohio, United States

St. Anne Mercy 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

Joan Karnell Cancer Center at Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, United States

Hematology and Oncology Associates of Northeastern Pennsylvania

Scranton, Pennsylvania, United States

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Fredericksburg Oncology, Incorporated

Fredericksburg, Virginia, United States

Marshfield Clinic - Chippewa Center

Chippewa Falls, Wisconsin, United States

Marshfield Clinic Cancer Care at Regional Cancer Center

Eau Claire, Wisconsin, United States

UW Cancer Center Johnson Creek

Johnson Creek, 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 - Lakeland Center

Minocqua, Wisconsin, United States

Ministry Medical Group at Saint Mary's Hospital

Rhinelander, Wisconsin, United States

Marshfield Clinic - Indianhead Center

Rice Lake, Wisconsin, United States

Marshfield Clinic at Saint Michael's Hospital

Stevens Point, Wisconsin, United States

Marshfield Clinic - Wausau Center

Wausau, Wisconsin, United States

Marshfield Clinic - Weston Center

Weston, Wisconsin, United States

Marshfield Clinic - Wisconsin Rapids Center

Wisconsin Rapids, Wisconsin, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

Other Identifiers

E3205

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA023318

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000470269

Identifier Type: REGISTRY

Identifier Source: secondary_id

E3205

Identifier Type: -

Identifier Source: org_study_id