Phase II Trial of FOLFOX6, Bevacizumab and Cetuximab in Patients With Colorectal Cancer

NCT00100841 | Completed Phase 2 Results DMC

• 4 other identifiers: NCI-2012-03006NCI-6490N01CM62201N01CM62204
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab and cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab and cetuximab may kill more tumor cells. This phase II trial is studying how well giving combination chemotherapy together with bevacizumab and cetuximab works in treating patients with stage IV colorectal cancer that cannot be removed by surgery.

Conditions

Adenocarcinoma of the Rectum; Mucinous Adenocarcinoma of the Colon; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Stage IV Colon Cancer; Stage IV Rectal Cancer

Outcome Measures

Primary Outcomes (2)

• Severe Adverse Event (SAE) Rate

  The primary objective is to evaluate safety in all treated patients specifically the rate of serious adverse events which were defined as grade 5 events, grade 4 hemorrhage or thrombosis or bowel perforation

  The duration of the study

• Progression Free Survival Rate

  From randomization to the first documented disease progression

Study Arms (1)

Treatment (combination chemotherapy)

EXPERIMENTAL

Patients receive cetuximab IV over 60-120 minutes on day 1 in weeks 1-8. Patients also receive bevacizumab IV over 30-90 minutes, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 48 hours on days 1 and 2 of weeks 1, 3, 5, and 7. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

Biological: cetuximab; Biological: bevacizumab; Drug: oxaliplatin; Drug: leucovorin calcium; Drug: fluorouracil

Interventions

cetuximab BIOLOGICAL

Given IV

Also known as: C225, C225 monoclonal antibody, IMC-C225, MOAB C225, monoclonal antibody C225

Treatment (combination chemotherapy)

bevacizumab BIOLOGICAL

Given IV

Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

Treatment (combination chemotherapy)

oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Dacotin, Dacplat, Eloxatin, L-OHP

Treatment (combination chemotherapy)

leucovorin calcium DRUG

Given IV

Also known as: CF, CFR, LV

Treatment (combination chemotherapy)

fluorouracil DRUG

Given IV

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU

Treatment (combination chemotherapy)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of the colon or rectum which is beyond the scope of surgical resection (MEDRA code:"Colorectal neoplasms malignant","Colorectal cancer stage IV","10010035")
• Measurable disease,
• Life expectancy of greater than 3 months
• ECOG performance status =\< 1
• Leukocytes \>= 3,500/uL
• Absolute neutrophil count \>= 1,500/uL
• Platelets \>= 150,000/uL
• Total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) =\< 2.5 X institutional upper limit of normal
• Creatinine within normal institutional limits
• Patients may not have received prior therapy with bevacizumab or cetuximab
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Patients who have had radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to radiotherapy administered more than 4 weeks earlier
• Patients may not be receiving any other investigational agents
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to any of the agents used in the study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or lactating women
• Serious or non-healing wound, ulcer or bone fracture
• Invasive procedures defined as follows:
• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy
• Anticipation of need for major surgical procedures during the course of the study
• Core biopsy within 7 days prior to D1 therapy
• If a patient is on full-dose anticoagulants, the following criteria should be met for enrollment:
• The subject must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin or on stable dose of LMW heparin
• The subject must not have active bleeding or pathological conditions that carry high risk of bleeding (e.g. tumor involving major vessels, known varices)
• Active infection requiring parental antibiotics on D1

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Montefiore Medical Center

The Bronx, New York, 10467-2490, United States

Location

Related Publications (1)

• Ocean AJ, Polite B, Christos P, Horvath L, Hamilton A, Matulich D, Chen HX, Sparano JA, Kindler HL. Cetuximab is associated with excessive toxicity when combined with bevacizumab Plus mFOLFOX6 in metastatic colorectal carcinoma. Clin Colorectal Cancer. 2010 Dec;9(5):290-6. doi: 10.3816/CCC.2010.n.042.

  PMID: 21208843 RESULT

MeSH Terms

Conditions

Rectal Neoplasms; Colonic Neoplasms

Interventions

Cetuximab; Bevacizumab; Oxaliplatin; Leucovorin; Fluorouracil

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; Colonic Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Lisa Escobar-Peralta
• Organization: Montefiore Medical Center

lescobar@montefiore.org

718-379-6866

Study Officials

• Allyson Ocean

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: January 6, 2005
• First Posted: January 7, 2005
• Study Start: November 1, 2004
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: July 27, 2015
• Results First Posted: July 27, 2015

Record last verified: 2013-07

Locations

US (1)