Cetuximab, 5-FU and Radiation as Neoadjuvant Therapy for Patients With Locally Advanced Rectal Cancer

This study has been terminated.
(Slow accrual)
Massachusetts General Hospital
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Bristol-Myers Squibb
Information provided by (Responsible Party):
Jeffrey A. Meyerhardt, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
First received: January 29, 2008
Last updated: January 20, 2016
Last verified: January 2016
The standard treatment for rectal cancer is to receive the chemotherapeutic drug 5-fluorouracil (5-FU) with radiation therapy before having surgery to remove the rectal cancer. This is known as neoadjuvant chemoradiotherapy. The purpose of this research study is to determine if Cetuximab improves the benefits of neoadjuvant chemoradiotherapy when given with 5-FU and radiation therapy. The epidermal growth factor (EGF) receptor, which is found in rectal cancer, is a specific part of the cancer that is felt to encourage tumor growth. Cetuximab targets and blocks the EGF receptor and has been shown to be safe and effective in treating colorectal cancer and head and neck cancers.

Condition Intervention Phase
Rectal Cancer
Drug: Cetuximab
Drug: 5-Fluorouracil
Radiation: External Beam Pelvis Radiation Therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Cetuximab, 5-FU and Radiation as Neoadjuvant Therapy for Patients With Locally Advanced Rectal Cancer

Resource links provided by NLM:

Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Determine the pathological complete response rate of cetuximab with standard 5-FU and radiation as neoadjuvant therapy in patients with stage II/III rectal cancer. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Determine complete resection rate, local recurrence rate, distance recurrence rate, disease free survival and overall survival in this patient population with this treatment. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Characterize toxicity profile of neoadjuvant therapy with cetuximab, 5-FU and radiation in this patient population. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Enrollment: 13
Study Start Date: January 2008
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Cetuximab
    Given once a week for 9 weeks
    Drug: 5-Fluorouracil
    Given by continuous infusion for weeks 4 through 9
    Other Name: 5-FU
    Radiation: External Beam Pelvis Radiation Therapy
    Monday through Friday beginning after the 2nd sigmoidoscopy and biopsy is completed
Detailed Description:
  • Prior to the first dose of cetuximab, participants will undergo a sigmoidoscopy with biopsy for research purposes as well collection of blood samples. These tests will be repeated between days 16 and 21.
  • After treatment begins, participants will undergo the following every week; history and physical exam; vital signs; blood tests.
  • On treatment weeks 1, 2 and 3: cetuximab is given once a week. On weeks 4 through 9: cetuximab is given weekly; continuous infusion of 5-FU will begin on day 22; treatment with radiation therapy Monday through Friday.
  • It is recommended that the participant undergo surgery 4 to 8 weeks after completion of therapy to attempt to remove the tumor.

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

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the rectum that begins within 15cm of the anal verge as determined by sigmoidoscopy and/or colonoscopy, with no evidence of distant metastatic disease. A complete colonoscopy to the cecum is recommended prior to initiating protocol therapy.
  • Staging with transrectal ultrasound or endorectal coil MRI to confirm clinical stage of T3 or T4 or lymph node positive rectal adenocarcinoma
  • Tumor is K-ras wildtype by method of choice at respective institution (testing codons 12 and 13)
  • Performance status: ECOG less than or equal to 2
  • 18 years of age or older
  • No evidence of metastatic disease by abdominal/pelvic CT and chest imaging
  • Adequate bone marrow, renal,and hepatic function as outlined in protocol
  • All patients will be evaluated by a surgeon and considered a candidate for definitive surgery
  • Coumadin or heparin management for line care of other indications is permitted. The INR will be monitored weekly in patients taking coumadin.

Exclusion Criteria:

  • Prior treatment for this malignancy
  • Prior history of pelvic radiation therapy
  • Prior history of 5-FU based or EGFR receptor inhibitor therapy
  • Prior history of an allergic reaction to a monoclonal antibody
  • Uncontrolled serious medical or psychiatric illness
  • Significant history of uncontrolled cardiac disease
  • Sexually active women of childbearing potential must use an effective method of birth control during the course of the study
  • Unwilling to agree to pre and post-cetuximab sigmoidoscopy and biopsy
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00611858

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
South Shore Hospital
Weymouth, Massachusetts, United States
United States, Tennessee
Vanderbilt Medical Center
Nashville, Tennessee, United States
Sponsors and Collaborators
Dana-Farber Cancer Institute
Massachusetts General Hospital
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Bristol-Myers Squibb
Principal Investigator: Jeffrey Meyerhardt, MD, MPH Dana-Farber Cancer Institute
  More Information

Responsible Party: Jeffrey A. Meyerhardt, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00611858     History of Changes
Other Study ID Numbers: 07-297  BMS CA225302 
Study First Received: January 29, 2008
Last Updated: January 20, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
adenocarcinoma of the rectum
neoadjuvant therapy

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms by Site
Rectal Diseases
Antineoplastic Agents

ClinicalTrials.gov processed this record on May 26, 2016