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

NCT00580073 | Terminated Phase 2 Results DMC

• 5 other identifiers: CO06207NCI-2011-00476A534260SMPH/MEDICINEH-2007-0197
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• 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).

  6 months

Secondary Outcomes (2)

• Progression Free Survival

  Up to 3 years

• Overall Survival

  Up to 3 years

Study Arms (1)

1

EXPERIMENTAL

FOLFOX4 + Cetuximab

Drug: FOLFOX4; Drug: Cetuximab

Interventions

FOLFOX4 DRUG

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)

Also known as: Oxaliplatin (Eloxatin), 5FU (5-Fluorouracil) and Leucovorin (Folinic Acid)

1

Cetuximab DRUG

Cetuximab 400mg/m2 on day 1 only, 250mg/mr on days 8, 15, and 22 of each cycle.

Also known as: Cetuximab (C225, Erbitux)

1

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Sanofi: collaborator
• Bristol-Myers Squibb: collaborator
• Eli Lilly and Company: collaborator

Study Sites (1)

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Folfox protocol; Oxaliplatin; Fluorouracil; Leucovorin; Cetuximab

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)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Study closed due to withdrawal of funding.

Results Point of Contact

• Title: CRA
• Organization: University of Wisconsin-Madison

smccarthy@medicine.wisc.edu

608-265-4347

Study Officials

• Michael Huie, M.D.

  UW Paul P. Carbone Comprehensive Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2007
• First Posted: December 24, 2007
• Study Start: December 1, 2007
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: December 13, 2019
• Results First Posted: May 1, 2017

Record last verified: 2017-03

Locations

US (1)