Official Title: “Phase II Study of Cetuximab, 5-FU and Radiation as Neoadjuvant Therapy for Patients With Locally Advanced Rectal Cancer”

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.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: January 2011

- 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.

Intervention(s) in this Clinical Trial

• Drug: Cetuximab
  • Given once a week for 9 weeks
• Drug: 5-Fluorouracil
  • Given by continuous infusion for weeks 4 through 9
• Radiation: External Beam Pelvis Radiation Therapy
  • Monday through Friday beginning after the 2nd sigmoidoscopy and biopsy is completed

Primary 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
    Safety Issue?: No

Secondary 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
    Safety Issue?: No
• Characterize toxicity profile of neoadjuvant therapy with cetuximab, 5-FU and radiation in this patient population.
  • Time Frame: 3 years
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Dana-Farber Cancer Institute

Overall Clinical Trial Officials and Contacts

Jeffrey Meyerhardt, MD, MPH Principal Investigator Dana-Farber Cancer Institute  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00611858

Study ID Number: 07-297

ClinicalTrials.gov Identifier: NCT00611858

Health Authority: United States: Institutional Review Board