Cetuximab, Capecitabine and Oxaliplatin in Patients With Epidermal Growth Factor Receptor (EGFr) Expressing Metastatic Colorectal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
ImClone LLC
Bristol-Myers Squibb
Information provided by:
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT00444678
First received: March 7, 2007
Last updated: May 7, 2014
Last verified: May 2014
  Purpose

This trial will examine the addition of Cetuximab in combination with Oxaliplatin and Capecitabine for treatment of patients with previously untreated metastatic colorectal cancer.


Condition Intervention Phase
Colorectal Cancer
Neoplasm Metastasis
Drug: Cetuximab
Drug: Oxaliplatin
Drug: Capecitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Cetuximab Plus Biweekly Capecitabine and Oxaliplatin (C-CO2) in the Treatment of Patients With EGFR-Expressing Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • Response rate for the combination treatment [ Time Frame: 6 months since the start of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity rates [ Time Frame: 1 year since the first treatment and every year after ] [ Designated as safety issue: Yes ]
  • Time to progression [ Time Frame: 6 months since the start of treatment and every 3 months after treatment ] [ Designated as safety issue: No ]
  • Survival [ Time Frame: 6 months since the start of treatment and every 3 months after treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 39
Study Start Date: June 2004
Estimated Study Completion Date: October 2014
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab, Capecitabine and Oxaliplatin Drug: Cetuximab
500 mg/m2, IV every two weeks
Other Names:
  • Erbitux
  • C225
Drug: Oxaliplatin
85 mg/m2, IV, q 2 weeks
Other Name: Eloxatin
Drug: Capecitabine
2500 mg, po bid x 7 days every two weeks
Other Name: Xeloda

Detailed Description:

The current treatment options for metastatic colon cancer are in need of further improvement. The three-drug combination of oxaliplatin with 5-FU/LV in the second-line treatment of metastatic colorectal cancer have shown a significant increase in response rate compared to 5-FU/LV alone. Oxaliplatin has recently been FDA-approved for this indication and is now a standard first-line agent in combination with a fluoropyrimidine. Cetuximab, a chimeric monoclonal antibody against the growth factor receptor, has shown activity with and without irinotecan in subjects with colorectal cancer refractory to irinotecan alone. Cetuximab has also been shown to be safe and effective when administered with infusional 5-FU/folinic acid plus irinotecan. These results suggest that the addition of cetuximab to fluoropyrimidine/oxaliplatin-based regimen in the 1st line setting should be explored. The use of the oral fluoropyrimidine, capecitabine, to replace infusional 5FU has been widely used for improved convenience and possible safety. We have chosen a modified biweekly CapeOx regimen due to its improved tolerance and response rate with a fixed dose of capecitabine given its widespread practice and ease of use.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must have signed an approved informed consent.
  • Histologically confirmed diagnosis of advanced adenocarcinoma of the colon or rectum, with KRAS wild type on mutational analysis.
  • No prior chemotherapy for metastatic disease (chemotherapy naive). Prior adjuvant therapy with 5FU/LV or IFL is permitted if completed at least six months prior to entering this study.
  • Measurable disease by RECIST criteria as defined in Section 3.3.1.
  • Subjects for whom tumor tissue is available for IHC testing for EGFR expression.
  • ECOG Performance Status 0-1.
  • Recovery in full from any previous surgical procedure.
  • Expected survival greater than 12 weeks.
  • Subjects at least 18 years of age.
  • Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the study in such a manner that the risk of pregnancy is minimized. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study medication.
  • Adequate hematologic function defined by an absolute neutrophil count (ANC) > 1,500/mm3, a platelet count > 100,000/mm3 .
  • Adequate hepatic function defined by a total bilirubin level no greater than 2.0 times the upper limit of normal (ULN) and AST and ALT levels noo greater than 2.5 times the ULN (AST and ALT levels no greater than 5 times the ULN in the presence of liver metastases).
  • Adequate renal function defined by a serum creatinine level no greater than 1.5 times the ULN.

Exclusion Criteria:

  • WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks after the study.
  • Women who are pregnant or breastfeeding.
  • Women with a positive pregnancy test on enrollment or prior to study drug administration.
  • Sexually active fertile men not using effective birth control if their partners are women of child-bearing potential.
  • Subjects with > Grade 1 neuropathy.
  • Any active or uncontrolled infection.
  • History of myocardial infarction within the previous six months or current clinical evidence of congestive heart failure.
  • History of any other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix) unless in complete remission and off all therapy for that cancer for at least 5 years.
  • Central nervous system metastases.
  • Pregnant or lactating women. Men and women of reproductive potential must agree to use an effective contraceptive method.
  • Medical or psychiatric disorders that would interfere with informed consent or make them a poor risk for participation in this trial.
  • Prior allergic reaction to chimerized or murine monoclonal antibody therapy or documented presence of human anti-mouse antibodies (HAMA).
  • Subjects receiving a prior investigational agent within 30 days.
  • Prior therapy with oxaliplatin, cetuximab, or prior therapy that targets the EGF pathway.
  • Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.
  • Mutation in the KRAS gene
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00444678

Locations
United States, New York
Bellevue Hospital
New York, New York, United States, 10016
New York University Langone Medical Center
New York, New York, United States, 10016
Sponsors and Collaborators
New York University School of Medicine
ImClone LLC
Bristol-Myers Squibb
Investigators
Principal Investigator: Deirdre Cohen, MD New York University School of Medicine
  More Information

No publications provided

Responsible Party: Deirdre Cohen, M.D., New York University School of Medicine
ClinicalTrials.gov Identifier: NCT00444678     History of Changes
Other Study ID Numbers: NYU# 04-10 H11817, CA225056
Study First Received: March 7, 2007
Last Updated: May 7, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by New York University School of Medicine:
Previously untreated metastatic colorectal cancer
Metastatic Colorectal Cancer
combined therapy
biologics therapy
antibody
chemotherapy
EGFR

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Capecitabine
Fluorouracil
Oxaliplatin
Cetuximab
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014