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

NCT ID: NCT00611858

Last Updated: 2019-01-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2016-09-30

Brief Summary

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.

Detailed Description

The epidermal growth factor receptor (EGFR) present in normal and tumor cells is involved in signaling pathways affecting cellular growth, differentiation, proliferation and programmed cell death. Overexpression of EGFR has been associated with poorer prognosis in colorectal cancer. Cetuximab targets and blocks EGFR and has been shown to be safe and effective in treating colorectal cancer and head and neck cancers.

The primary hypothesis is that cetuximab in combination with standard 5-FU and radiation as neoadjuvant therapy would improve pathological complete response (pCR) compared to the historical rate (30% versus 10%). The regimen would be considered promising if 5 or more of 25 evaluable participants achieve pCR. The probability of observing this outcome is 0.91 and 0.10 if the true pCR rate is 30% and 10%, respectively.

Conditions

Rectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cetuximab, 5-FU and Radiation

Cetuximab: Participants first receive cetuximab at the initial dose of 400 mg/m2 intravenously (IV) administered over 120 minutes, followed by weekly infusions at 250 mg/m2 over 60 minutes. Cetuximab is given as single agent during the first 3 weeks on study and then in combination with 5-FU and radiation.

Radiation: Radiation therapy given as standard of care is initiated after the 3rd dose of cetuximab with a total dose of 50.4 Gray (Gy) in 28 fractions over approximately 5.5 weeks.

5-FU: Participants receive 5-Fluorouracil (5-FU) continuous infusion through central venous access at 225 mg/m2/day given 7 days a week starting day 1 of radiation (no later than 3 days) and lasting the duration of radiation therapy.

Duration of neoadjuvant therapy is estimated to be 9 weeks. Surgery follows at week 13-17. Sigmoidoscopy is performed for biopsy prior to the 1st dose and after 3rd dose of cetuximab before the initiation of radiation and/or 5-FU.

Group Type: EXPERIMENTAL

Cetuximab

Intervention Type: DRUG

5-Fluorouracil

Intervention Type: DRUG

Radiation

Intervention Type: RADIATION

Interventions

Cetuximab

Intervention Type: DRUG

5-Fluorouracil

Intervention Type: DRUG

Radiation

Intervention Type: RADIATION

Other Intervention Names

Erbitux; 5-FU; External Beam Radiation Therapy

Eligibility Criteria

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 Magnetic resonance imaging (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: Eastern Cooperative Oncology Group Performance Score (ECOG PS) less than or equal to 2
• 18 years of age or older
• No evidence of metastatic disease by abdominal/pelvic (Computed tomography) 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 International Normalised Ratio (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

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

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Jeffrey A. Meyerhardt, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeffrey Meyerhardt, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

South Shore Hospital

Weymouth, Massachusetts, United States

Vanderbilt Medical Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

BMS CA225302

Identifier Type: -

Identifier Source: secondary_id

07-297

Identifier Type: -

Identifier Source: org_study_id