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

Rectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00611858
• Other study ID #: 07-297
• Secondary ID: BMS CA225302
• Status: Terminated
• Phase: Phase 2
• Start date: May 2008
• Est. completion date: September 2016

Study information

• Verified date: December 2018
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: September 2016
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• Cetuximab

• 5-Fluorouracil

Radiation:
• Radiation

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Vanderbilt Medical Center	Nashville	Tennessee
United States	South Shore Hospital	Weymouth	Massachusetts

Sponsors (5)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Bristol-Myers Squibb, Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	1-Year Disease-Free Survival Rate	Disease-Free Survival Rate is the percentage of participants remaining alive without disease progression.	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.
Primary	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	Local Recurrence Rate	Local recurrence rate is the percentage of participants experiencing recurrence within the pelvis.	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.
Secondary	Complete Resection Rate	Complete resection rate is the percentage of participants having all gross disease removed by the surgeon at the time of operation.	Disease is assessed at the time of surgery which in this study cohort occurred up to 24 weeks from date of registration.
Secondary	Distant Recurrence Rate	Distant recurrence rate is the percentage of participants experiencing recurrence outside the pelvis.	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.
Secondary	Incidence of Grade 4 Treatment-Related Toxicity	All grade 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3) as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 4 AE of any type during the time of observation.	Disease is assessed through the time of surgery which in this study cohort occurred up to 24 weeks from date of registration.
Secondary	1-Year Overall Survival Rate	1-year overall survival is the percentage of participants remaining alive 1 year from study entry.	Mean follow-up for this study cohort was 4.4 years from study entry, up to 7.9 years.