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Phase II Trial of Neoadjuvant FOLFOX4 and Cetuximab for Localized Adenocarcinoma of Rectum

Primary Purpose

Rectal Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
FOLFOX4
Cetuximab
Sponsored by
University of Wisconsin, Madison
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rectal Cancer

Eligibility Criteria

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

Inclusion Criteria:

  • All patients must have newly diagnosed, histologically proven adenocarcinoma of the rectum. Locally advanced T3, T4 or any T with N1, N2, staged by trans-rectal ultrasound.
  • All patients must have an abdominal/pelvis CT scan or MRI confirming no evidence of distant metastases.
  • Patients must have an ECOG PS ≤ 2
  • Patient has signed informed consent
  • Lower Age Limit: 18 years
  • Upper Age Limit: No upper age limit

  • Laboratory parameters:

    • Hgb: > 9.0 g/dl
    • ANC >1500/ul
    • Platelet >100,000/ul
    • Creatinine < 2x ULN
    • Bilirubin < 2x ULN
    • ALT < 2x ULN

Exclusion Criteria:

  • Administration of any prior systemic anticancer therapy for colorectal cancer (eg, chemotherapy, antibody therapy, immunotherapy, gene therapy, vaccine therapy, cytokine therapy, angiogenesis inhibitors).
  • Previous intra-arterial cytotoxic chemotherapy given as treatment for colorectal cancer.
  • Previous pelvic radiotherapy.
  • Known allergy or intolerance to oxaliplatin, 5-FU, cetuximab or leucovorin.
  • Pregnant or breast-feeding women: female patients must agree to use effective contraception, must be surgically sterile, or must be postmenopausal. Male patients must agree to use effective contraception or be surgically sterile. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. All at-risk female patients must have a negative serum pregnancy test within 7 days prior to registration.
  • Active inflammatory bowel disease, significant bowel obstruction, or chronic diarrhea (grade 2).
  • Myocardial infarction or stroke within the previous 6 months, or ongoing unstable angina, symptomatic congestive heart failure, or serious uncontrolled cardiac dysrhythmia.
  • Known human immunodeficiency virus (HIV) positivity or acquired-immunodeficiency-syndrome (AIDS)-related illness.
  • No previous or concurrent malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer for which the patient has been disease-free for 3 years.
  • Known CNS metastases
  • Preexisting neuropathy > Grade 2
  • Prior therapy which specifically and directly targets the EGFR pathway
  • Prior severe infusion reaction to a monoclonal antibody
  • Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure and cardiomyopathy with decreased ejection fraction.

Sites / Locations

  • University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

FOLFOX4 + Cetuximab

Outcomes

Primary Outcome Measures

Down-staging of the Tumor; Response to Therapy
Down-staging of the tumor and tumor response rate is defined as the proportion of participant who have any evidence of complete response (CR), pathologic complete response (pCR), or partial response (PR).

Secondary Outcome Measures

Progression Free Survival
Number of participants who achieve progression free survival, defined as the time from date of registration to date of disease progression, up through study closure. Progressive disease is defined as ≥ 20% increase in the sum of the longest dimensions of the primary lesion taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of 1 or more new lesions.
Overall Survival
Overall survival is defined as the time from date of registration to date of death. In the absence of confirmation of death, survival time will be censored at the last date of follow-up.

Full Information

First Posted
December 17, 2007
Last Updated
December 11, 2019
Sponsor
University of Wisconsin, Madison
Collaborators
Sanofi, Bristol-Myers Squibb, Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT00580073
Brief Title
Phase II Trial of Neoadjuvant FOLFOX4 and Cetuximab for Localized Adenocarcinoma of Rectum
Official Title
A Phase II Trial of Neoadjuvant FOLFOX4 and Cetuximab for Localized Adenocarcinoma of the Rectum
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Terminated
Why Stopped
Loss of funding
Study Start Date
December 2007 (undefined)
Primary Completion Date
November 2009 (Actual)
Study Completion Date
November 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Wisconsin, Madison
Collaborators
Sanofi, Bristol-Myers Squibb, Eli Lilly and Company

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study involves the use of Oxaliplatin, 5-Fluorouracil (5-FU), Leucovorin and Cetuximab, which are all medicines approved by the Food and Drug Administration (FDA) and are commercially available. This treatment regimen will possibly be combined with radiation before and/or after surgery depending on your response to the treatment. Their use in this exact combination is considered experimental. The purpose of this study is to find out how effective this combination of chemotherapy is as treatment for rectal cancer that has not spread to other parts of the body. The side effects and survival experienced by subjects receiving these drugs will also be evaluated. This is a phase II research study.
Detailed Description
Primary Objective: - Down-staging of the tumor Secondary Objectives: Pathologic response rate Tumor marker response Incidence of sphincter sparing surgery Progression-free survival Overall Survival

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Cancer

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
FOLFOX4 + Cetuximab
Intervention Type
Drug
Intervention Name(s)
FOLFOX4
Other Intervention Name(s)
Oxaliplatin (Eloxatin), 5FU (5-Fluorouracil) and Leucovorin (Folinic Acid)
Intervention Description
oxaliplatin (85mg/m2 on days 1 and 15 of each cycle)+ 5FU Bolus (400mg/m2 on days 1, 2, 15, and 16 of each cycle) + 5FU CI (600mg/m2 on days 1, 2, 15, and 16 of each cycle) + Leucovorin (200mg/m2 on days 1, 2, 15, and 16 of each cycle)
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Cetuximab (C225, Erbitux)
Intervention Description
Cetuximab 400mg/m2 on day 1 only, 250mg/mr on days 8, 15, and 22 of each cycle.
Primary Outcome Measure Information:
Title
Down-staging of the Tumor; Response to Therapy
Description
Down-staging of the tumor and tumor response rate is defined as the proportion of participant who have any evidence of complete response (CR), pathologic complete response (pCR), or partial response (PR).
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Progression Free Survival
Description
Number of participants who achieve progression free survival, defined as the time from date of registration to date of disease progression, up through study closure. Progressive disease is defined as ≥ 20% increase in the sum of the longest dimensions of the primary lesion taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of 1 or more new lesions.
Time Frame
Up to 3 years
Title
Overall Survival
Description
Overall survival is defined as the time from date of registration to date of death. In the absence of confirmation of death, survival time will be censored at the last date of follow-up.
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All patients must have newly diagnosed, histologically proven adenocarcinoma of the rectum. Locally advanced T3, T4 or any T with N1, N2, staged by trans-rectal ultrasound. All patients must have an abdominal/pelvis CT scan or MRI confirming no evidence of distant metastases. Patients must have an ECOG PS ≤ 2 Patient has signed informed consent Lower Age Limit: 18 years Upper Age Limit: No upper age limit Laboratory parameters: Hgb: > 9.0 g/dl ANC >1500/ul Platelet >100,000/ul Creatinine < 2x ULN Bilirubin < 2x ULN ALT < 2x ULN Exclusion Criteria: Administration of any prior systemic anticancer therapy for colorectal cancer (eg, chemotherapy, antibody therapy, immunotherapy, gene therapy, vaccine therapy, cytokine therapy, angiogenesis inhibitors). Previous intra-arterial cytotoxic chemotherapy given as treatment for colorectal cancer. Previous pelvic radiotherapy. Known allergy or intolerance to oxaliplatin, 5-FU, cetuximab or leucovorin. Pregnant or breast-feeding women: female patients must agree to use effective contraception, must be surgically sterile, or must be postmenopausal. Male patients must agree to use effective contraception or be surgically sterile. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. All at-risk female patients must have a negative serum pregnancy test within 7 days prior to registration. Active inflammatory bowel disease, significant bowel obstruction, or chronic diarrhea (grade 2). Myocardial infarction or stroke within the previous 6 months, or ongoing unstable angina, symptomatic congestive heart failure, or serious uncontrolled cardiac dysrhythmia. Known human immunodeficiency virus (HIV) positivity or acquired-immunodeficiency-syndrome (AIDS)-related illness. No previous or concurrent malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer for which the patient has been disease-free for 3 years. Known CNS metastases Preexisting neuropathy > Grade 2 Prior therapy which specifically and directly targets the EGFR pathway Prior severe infusion reaction to a monoclonal antibody Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure and cardiomyopathy with decreased ejection fraction.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Huie, M.D.
Organizational Affiliation
UW Paul P. Carbone Comprehensive Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Phase II Trial of Neoadjuvant FOLFOX4 and Cetuximab for Localized Adenocarcinoma of Rectum

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