search
Back to results

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

Primary Purpose

Rectal Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cetuximab
5-Fluorouracil
Radiation
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rectal Cancer focused on measuring 5-FU, cetuximab, radiation, adenocarcinoma of the rectum, neoadjuvant therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts General Hospital
  • Dana-Farber Cancer Institute
  • South Shore Hospital
  • Vanderbilt Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cetuximab, 5-FU and Radiation

Arm Description

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Local Recurrence Rate
Local recurrence rate is the percentage of participants experiencing recurrence within the pelvis.
Complete Resection Rate
Complete resection rate is the percentage of participants having all gross disease removed by the surgeon at the time of operation.
Distant Recurrence Rate
Distant recurrence rate is the percentage of participants experiencing recurrence outside the pelvis.
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.
1-Year Overall Survival Rate
1-year overall survival is the percentage of participants remaining alive 1 year from study entry.

Full Information

First Posted
January 29, 2008
Last Updated
December 17, 2018
Sponsor
Dana-Farber Cancer Institute
Collaborators
Massachusetts General Hospital, Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Bristol-Myers Squibb
search

1. Study Identification

Unique Protocol Identification Number
NCT00611858
Brief Title
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

2. Study Status

Record Verification Date
December 2018
Overall Recruitment Status
Terminated
Why Stopped
Slow accrual
Study Start Date
May 2008 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
September 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Massachusetts General Hospital, Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Cancer
Keywords
5-FU, cetuximab, radiation, adenocarcinoma of the rectum, neoadjuvant therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cetuximab, 5-FU and Radiation
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux
Intervention Type
Drug
Intervention Name(s)
5-Fluorouracil
Other Intervention Name(s)
5-FU
Intervention Type
Radiation
Intervention Name(s)
Radiation
Other Intervention Name(s)
External Beam Radiation Therapy
Primary Outcome Measure Information:
Title
Pathological Complete Response Rate
Description
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).
Time Frame
Disease is assessed at the time of surgery which in this study cohort occurred up to 24 weeks from date of registration.
Secondary Outcome Measure Information:
Title
Local Recurrence Rate
Description
Local recurrence rate is the percentage of participants experiencing recurrence within the pelvis.
Time Frame
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.
Title
Complete Resection Rate
Description
Complete resection rate is the percentage of participants having all gross disease removed by the surgeon at the time of operation.
Time Frame
Disease is assessed at the time of surgery which in this study cohort occurred up to 24 weeks from date of registration.
Title
Distant Recurrence Rate
Description
Distant recurrence rate is the percentage of participants experiencing recurrence outside the pelvis.
Time Frame
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.
Title
Incidence of Grade 4 Treatment-Related Toxicity
Description
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.
Time Frame
Disease is assessed through the time of surgery which in this study cohort occurred up to 24 weeks from date of registration.
Title
1-Year Overall Survival Rate
Description
1-year overall survival is the percentage of participants remaining alive 1 year from study entry.
Time Frame
Mean follow-up for this study cohort was 4.4 years from study entry, up to 7.9 years.
Other Pre-specified Outcome Measures:
Title
1-Year Disease-Free Survival Rate
Description
Disease-Free Survival Rate is the percentage of participants remaining alive without disease progression.
Time Frame
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey Meyerhardt, MD, MPH
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
South Shore Hospital
City
Weymouth
State/Province
Massachusetts
Country
United States
Facility Name
Vanderbilt Medical Center
City
Nashville
State/Province
Tennessee
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs