Clinical trial NCT00316888: Cetuximab, Cisplatin, Fluorouracil, and Radiation Therapy in Treating Patients With Anal Cancer
Official title: Phase II Trial of Cetuximab Plus Cisplatin, 5- Fluorouracil and Radiation in Immunocompetent Patients With Anal Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anal Cancer
Keywords: squamous cell carcinoma of the anus
stage I anal cancer
stage II anal cancer
stage IIIA anal cancer
stage IIIB anal cancer
basaloid carcinoma of the anus
cloacogenic carcinoma of the anus
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-04-21
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Local Failure Rate at 3 Years
timeFrame: assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3
Secondary outcomes:
measure: 3-year Overall Survival Rate
timeFrame: assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3
measure: 3-year Progression-free Survival Rate
timeFrame: assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3
measure: Objective Response Rate
timeFrame: 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
measure: 3-year Colostomy-free Survival Rate
timeFrame: assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Fort Collins
country: United States
facility: Poudre Valley Hospital
state: Colorado
city: Fort Collins
country: United States
facility: Front Range Cancer Specialists
state: Colorado
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Hematology and Oncology Associates
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Institute
state: Illinois
city: Highland Park
country: United States
facility: Kellogg Cancer Care Center
state: Illinois
city: Kankakee
country: United States
facility: Provena St. Mary's Regional Cancer Center - Kankakee
state: Illinois
city: Libertyville
country: United States
facility: North Shore Oncology and Hematology Associates, Limited - Libertyville
state: Illinois
city: Niles
country: United States
facility: Cancer Care and Hematology Specialists of Chicagoland - Niles
state: Illinois
city: Rockford
country: United States
facility: Swedish-American Regional Cancer Center
state: Illinois
city: Skokie
country: United States
facility: Hematology Oncology Associates - Skokie
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: William N. Wishard Memorial Hospital
state: Indiana
city: Cedar Rapids
country: United States
facility: Cedar Rapids Oncology Associates
state: Iowa
city: Cedar Rapids
country: United States
facility: Mercy Regional Cancer Center at Mercy Medical Center
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center - Sioux City
state: Iowa
city: Sioux City
country: United States
facility: St. Luke's Regional Medical Center
state: Iowa
city: Chanute
country: United States
facility: Cancer Center of Kansas, PA - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas, PA - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, PA - El Dorado
state: Kansas
city: Fort Scott
country: United States
facility: Cancer Center of Kansas - Fort Scott
state: Kansas
city: Independence
country: United States
facility: Cancer Center of Kansas-Independence
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas, PA - Kingman
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Liberal
country: United States
facility: Cancer Center of Kansas, PA - Liberal
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas, PA - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, PA - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas, PA - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas, PA - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas, PA - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health, PA - North Review
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas, PA - Winfield
state: Kansas
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center - Baton Rouge
state: Louisiana
city: New Orleans
country: United States
facility: MBCCOP - LSU Health Sciences Center
state: Louisiana
city: New Orleans
country: United States
facility: Medical Center of Louisiana - New Orleans
state: Louisiana
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center Cancer Center
state: Maryland
city: Adrian
country: United States
facility: Hickman Cancer Center at Bixby Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Monroe
country: United States
facility: Community Cancer Center of Monroe
state: Michigan
city: Monroe
country: United States
facility: Mercy Memorial Hospital - Monroe
state: Michigan
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy and Unity Cancer Center at Mercy Hospital
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Mercy and Unity Cancer Center at Unity Hospital
state: Minnesota
city: Hutchinson
country: United States
facility: Hutchinson Area Health Care
state: Minnesota
city: Maplewood
country: United States
facility: HealthEast Cancer Care at St. John's Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology - Maplewood
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center - Minneapolis
state: Minnesota
city: Robbinsdale
country: United States
facility: Humphrey Cancer Center at North Memorial Outpatient Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Cancer Center
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital Cancer Care Center
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Shakopee
country: United States
facility: St. Francis Cancer Center at St. Francis Medical Center
state: Minnesota
city: Stillwater
country: United States
facility: Lakeview Hospital
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Willmar
country: United States
facility: Willmar Cancer Center at Rice Memorial Hospital
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology - Woodbury
state: Minnesota
city: Lincoln
country: United States
facility: Cancer Resource Center - Lincoln
state: Nebraska
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Omaha
country: United States
facility: Immanuel Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Alegant Health Cancer Center at Bergan Mercy Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Lakeside Hospital
state: Nebraska
city: Omaha
country: United States
facility: Creighton University Medical Center
state: Nebraska
city: Morristown
country: United States
facility: Carol G. Simon Cancer Center at Morristown Memorial Hospital
state: New Jersey
city: Summit
country: United States
facility: Overlook Hospital
state: New Jersey
city: Bronx
country: United States
facility: Albert Einstein Cancer Center at Albert Einstein College of Medicine
state: New York
city: New York
country: United States
facility: NYU Cancer Institute at New York University Medical Center
state: New York
city: Bowling Green
country: United States
facility: Wood County Oncology Center
state: Ohio
city: Chillicothe
country: United States
facility: Adena Regional Medical Center
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital Cancer Care
state: Ohio
city: Columbus
country: United States
facility: CCOP - Columbus
state: Ohio
city: Columbus
country: United States
facility: Grant Medical Center Cancer Care
state: Ohio
city: Columbus
country: United States
facility: Mount Carmel Health - West Hospital
state: Ohio
city: Columbus
country: United States
facility: Doctors Hospital at Ohio Health
state: Ohio
city: Delaware
country: United States
facility: Grady Memorial Hospital
state: Ohio
city: Elyria
country: United States
facility: Community Cancer Center
state: Ohio
city: Elyria
country: United States
facility: Hematology Oncology Center
state: Ohio
city: Lancaster
country: United States
facility: Fairfield Medical Center
state: Ohio
city: Lima
country: United States
facility: Lima Memorial Hospital
state: Ohio
city: Marietta
country: United States
facility: Strecker Cancer Center at Marietta Memorial Hospital
state: Ohio
city: Maumee
country: United States
facility: Northwest Ohio Oncology Center
state: Ohio
city: Mount Vernon
country: United States
facility: Knox Community Hospital
state: Ohio
city: Newark
country: United States
facility: Licking Memorial Cancer Care Program at Licking Memorial Hospital
state: Ohio
city: Oregon
country: United States
facility: St. Charles Mercy Hospital
state: Ohio
city: Oregon
country: United States
facility: Toledo Clinic - Oregon
state: Ohio
city: Portsmouth
country: United States
facility: Southern Ohio Medical Center Cancer Center
state: Ohio
city: Springfield
country: United States
facility: Community Hospital of Springfield and Clark County
state: Ohio
city: Sylvania
country: United States
facility: Flower Hospital Cancer Center
state: Ohio
city: Tiffin
country: United States
facility: Mercy Hospital of Tiffin
state: Ohio
city: Toledo
country: United States
facility: Toledo Hospital
state: Ohio
city: Toledo
country: United States
facility: St. Vincent Mercy Medical Center
state: Ohio
city: Toledo
country: United States
facility: Medical University of Ohio Cancer Center
state: Ohio
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital
state: Ohio
city: Toledo
country: United States
facility: St. Anne Mercy Hospital
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic, Incorporated - Main Clinic
state: Ohio
city: Wauseon
country: United States
facility: Fulton County Health Center
state: Ohio
city: Zanesville
country: United States
facility: Genesis - Good Samaritan Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Joan Karnell Cancer Center at Pennsylvania Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center - Philadelphia
state: Pennsylvania
city: Scranton
country: United States
facility: Hematology and Oncology Associates of Northeastern Pennsylvania
state: Pennsylvania
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Fredericksburg
country: United States
facility: Fredericksburg Oncology, Incorporated
state: Virginia
city: Chippewa Falls
country: United States
facility: Marshfield Clinic - Chippewa Center
state: Wisconsin
city: Eau Claire
country: United States
facility: Marshfield Clinic Cancer Care at Regional Cancer Center
state: Wisconsin
city: Johnson Creek
country: United States
facility: UW Cancer Center Johnson Creek
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic - Marshfield Center
state: Wisconsin
city: Minocqua
country: United States
facility: Marshfield Clinic - Lakeland Center
state: Wisconsin
city: Rhinelander
country: United States
facility: Ministry Medical Group at Saint Mary's Hospital
state: Wisconsin
city: Rice Lake
country: United States
facility: Marshfield Clinic - Indianhead Center
state: Wisconsin
city: Stevens Point
country: United States
facility: Marshfield Clinic at Saint Michael's Hospital
state: Wisconsin
city: Wausau
country: United States
facility: Marshfield Clinic - Wausau Center
state: Wisconsin
city: Weston
country: United States
facility: Marshfield Clinic - Weston Center
state: Wisconsin
city: Wisconsin Rapids
country: United States
facility: Marshfield Clinic - Wisconsin Rapids Center
state: Wisconsin
Study officials:
affiliation: Montefiore Medical Center
name: Madhur K. Garg, MD
role: STUDY_CHAIR
affiliation: Montefiore Medical Center
name: Joseph A. Sparano, MD
role: STUDY_CHAIR
References:
citation: 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.