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Cetuximab, Cisplatin, Fluorouracil, and Radiation Therapy in Treating Patients With Stage I, Stage II, or Stage III Anal Cancer

This study is currently recruiting participants.
Verified July 2012 by National Cancer Institute (NCI)
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00316888
First received: April 19, 2006
Last updated: August 22, 2012
Last verified: July 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Anal Cancer
 Biological: cetuximab
Drug: cisplatin
Drug: fluorouracil
Radiation: radiation therapy
 Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Cetuximab Plus Cisplatin, 5- Fluorouracil and Radiation in Immunocompetent Patients With Anal Carcinoma

Resource links provided by NLM:

MedlinePlus related topics: Anal Cancer Cancer
U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Local failure rate at 3 years [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response (complete and partial response) [ Designated as safety issue: No ]
  • Time to disease progression as measured by descriptive statistics [ Designated as safety issue: No ]
  • Response duration as measured by the Kaplan-Meier method [ Designated as safety issue: No ]
  • Progression-free survival as measured by the Kaplan-Meier method [ Designated as safety issue: No ]
  • Colostomy-free survival as measured by the Kaplan-Meier method [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]

Estimated Enrollment: 62
Study Start Date: January 2007
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
 Biological: cetuximab
Given IV
Drug: cisplatin
Given IV
Drug: fluorouracil
Given IV
Radiation: radiation therapy
Given once daily 5 days a week for 5 weeks
Experimental: Arm II
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.
 Biological: cetuximab
Given IV
Drug: cisplatin
Given IV
Drug: fluorouracil
Given IV
Radiation: radiation therapy
Given once daily 5 days a week for 5 weeks

Detailed Description:

OBJECTIVES:

Primary

  • 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-IIIB invasive anal carcinoma.

Secondary

  • Determine objective response rate (complete and partial), progression-free survival, relapse-free survival, colostomy-free survival, and overall survival.
  • Determine the overall toxicity of concurrent cisplatin, fluorouracil, and radiation therapy combined with cetuximab.
  • 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, PI3K, and P-Akt (as determined by immunohistochemistry) is associated with an increased risk of local failure.

OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 treatment arms.

  • 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.
  • Arm II: 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. Treatment continues in the absence of disease progression or unacceptable toxicity.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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
  • AST and ALT < 3 times ULN
  • Not pregnant or nursing
  • 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

  • None 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
  • No history of rheumatic disorders, irritable bowel syndrome, or inflammatory bowel disease
  • No known HIV positivity

  • No known risk factors for HIV infection

    • Patients with a known risk factor for 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 RNA

PRIOR CONCURRENT THERAPY:

  • No prior radiotherapy or chemotherapy for this malignancy
  • No prior pelvic radiotherapy
  • No prior potentially curative surgery (i.e., abdominal or peritoneal resection) for anal cancer
  • No concurrent intensity-modulated radiotherapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00316888

  Show 125 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Investigators
Study Chair: Madhur K. Garg, MD Montefiore Medical Center
Investigator: Joseph A. Sparano, MD Montefiore Medical Center
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Robert L. Comis, ECOG Group Chair's Office
ClinicalTrials.gov Identifier: NCT00316888     History of Changes
Other Study ID Numbers: CDR0000470269, ECOG-E3205
Study First Received: April 19, 2006
Last Updated: August 22, 2012
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Anus Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Anus Diseases
Rectal Diseases
 Cetuximab
Cisplatin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on May 19, 2013