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

NCT00611858 | Terminated Phase 2 Results DMC

• 2 other identifiers: 07-297BMS CA225302
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 4

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.

Conditions

Rectal Cancer

Keywords

5-FU; cetuximab; radiation; adenocarcinoma of the rectum; neoadjuvant therapy

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response Rate

  Pathological complete response (pCR) rate is the percentage of participants who achieve pCR defined as no evidence of tumor cells in the surgical specimen including the lymph nodes (down-staging to pathological T0, N0 after planned neoadjuvant therapy).

  Disease is assessed at the time of surgery which in this study cohort occurred up to 24 weeks from date of registration.

Secondary Outcomes (5)

• Local Recurrence Rate

  CT scans for surveillance recommended yearly x 3 years from date of surgery with additional scanning at discretion of treating oncologist. Mean follow-up for this study cohort was 4.4 years from study entry, up to 7.9 years.

• Complete Resection Rate

  Disease is assessed at the time of surgery which in this study cohort occurred up to 24 weeks from date of registration.

• Distant Recurrence Rate

  CT scans for surveillance recommended yearly x 3 years from date of surgery with additional scanning at discretion of treating oncologist. Mean follow-up for this study cohort was 4.4 years from study entry, up to 7.9 years.

• Incidence of Grade 4 Treatment-Related Toxicity

  Disease is assessed through the time of surgery which in this study cohort occurred up to 24 weeks from date of registration.

• 1-Year Overall Survival Rate

  Mean follow-up for this study cohort was 4.4 years from study entry, up to 7.9 years.

Other Outcomes (1)

• 1-Year Disease-Free Survival Rate

  CT scans for surveillance recommended yearly x 3 years from date of surgery with additional scanning at discretion of treating oncologist. Mean follow-up for this study cohort was 4.4 years from study entry, up to 7.9 years.

Study Arms (1)

Cetuximab, 5-FU and Radiation

EXPERIMENTAL

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.

Drug: Cetuximab; Drug: 5-Fluorouracil; Radiation: Radiation

Interventions

Cetuximab DRUG

Also known as: Erbitux

Cetuximab, 5-FU and Radiation

5-Fluorouracil DRUG

Also known as: 5-FU

Cetuximab, 5-FU and Radiation

Radiation RADIATION

Also known as: External Beam Radiation Therapy

Cetuximab, 5-FU and Radiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Massachusetts General Hospital: collaborator
• Beth Israel Deaconess Medical Center: collaborator
• Brigham and Women's Hospital: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (4)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

South Shore Hospital

Weymouth, Massachusetts, United States

Location

Vanderbilt Medical Center

Nashville, Tennessee, United States

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Cetuximab; Fluorouracil; Radiation

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Physical Phenomena

Limitations and Caveats

This study was terminated early due to weak accrual.

Results Point of Contact

• Title: Jeffrey Meyerhardt, MD, MPH
• Organization: Dana-Farber Cancer Institute

Jeffrey_Meyerhardt@dfci.harvard.edu

617-632-6855

Study Officials

• Jeffrey Meyerhardt, MD, MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 29, 2008
• First Posted: February 11, 2008
• Study Start: May 1, 2008
• Primary Completion: December 1, 2012
• Study Completion: September 1, 2016
• Last Updated: January 8, 2019
• Results First Posted: November 14, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)