Clinical trial NCT00611858: Cetuximab, 5-FU and Radiation as Neoadjuvant Therapy for Patients With Locally Advanced Rectal Cancer
Official title: Phase II Study of Cetuximab, 5-FU and Radiation as Neoadjuvant Therapy for Patients With Locally Advanced Rectal Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: 5-FU
cetuximab
radiation
adenocarcinoma of the rectum
neoadjuvant therapy
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Massachusetts General Hospital
name: Beth Israel Deaconess Medical Center
name: Brigham and Women's Hospital
name: Bristol-Myers Squibb
First posted: 2008-02-11
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Pathological Complete Response Rate
timeFrame: Disease is assessed at the time of surgery which in this study cohort occurred up to 24 weeks from date of registration.
Secondary outcomes:
measure: Local Recurrence Rate
timeFrame: 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.
measure: Complete Resection Rate
timeFrame: Disease is assessed at the time of surgery which in this study cohort occurred up to 24 weeks from date of registration.
measure: Distant Recurrence Rate
timeFrame: 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.
measure: Incidence of Grade 4 Treatment-Related Toxicity
timeFrame: Disease is assessed through the time of surgery which in this study cohort occurred up to 24 weeks from date of registration.
measure: 1-Year Overall Survival Rate
timeFrame: Mean follow-up for this study cohort was 4.4 years from study entry, up to 7.9 years.
Other outcomes:
measure: 1-Year Disease-Free Survival Rate
timeFrame: 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.
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Weymouth
country: United States
facility: South Shore Hospital
state: Massachusetts
city: Nashville
country: United States
facility: Vanderbilt Medical Center
state: Tennessee
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Jeffrey Meyerhardt, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: