Combination Chemotherapy Plus Cetuximab in Treating Patients With Liver Metastases From Colorectal Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00056030
First received: March 6, 2003
Last updated: June 17, 2012
Last verified: January 2009
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining chemotherapy with cetuximab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with cetuximab works in treating patients with unresectable liver metastases from colorectal cancer.


Condition Intervention Phase
Colorectal Cancer
Metastatic Cancer
Biological: cetuximab
Drug: fluorouracil
Drug: leucovorin calcium
Drug: oxaliplatin
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study Of Oxaliplatin (OXAL), 5-Fluorouracil (5-FU), Leucovorin (CF), and Cetuximab (C225) For Patients With Unresectable Hepatic Metastases From Metastatic Adenocarcinoma Of The Colon Or Rectum

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Surgical resectability rate as assessed by surgical resection of liver metastases [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate as measured by RECIST criteria every 6 weeks [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Quality of life as assessed by UNISCALE and Symptom Distress Scale every 6 weeks [ Designated as safety issue: No ]

Estimated Enrollment: 73
Study Start Date: December 2004
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the surgical resectability rate of patients with unresectable hepatic metastases secondary to metastatic colorectal adenocarcinoma treated with oxaliplatin, fluorouracil, leucovorin calcium, and cetuximab.
  • Determine the response rate and overall survival of patients treated with this regimen.
  • Determine the quality of life of patients treated with this regimen.
  • Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive cetuximab IV over 1 hour (over 2 hours on day 1 of course 1 only) on days 1 and 8. Patients also receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously on days 1-2. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity, for a minimum of 12 courses or until deemed to have resectable disease.

Quality of life is assessed at baseline and prior to each treatment course.

Patients are followed every 3 months for 1 year and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 67-73 patients will be accrued for this study within 4 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • History of completely resected primary adenocarcinoma of the colon or rectum

    • No gross or microscopic evidence of residual disease
  • Liver metastases, meeting 1 of the following criteria:

    • Not optimally resectable
    • Requires resection of all 3 major hepatic veins, the portal vein bifurcation, or the retrohepatic vena cava
    • Includes the main right or main left portal vein and the main hepatic vein of the opposite lobe
    • Requires more than a right or left trisegmentectomy
    • At least 6 metastatic lesions distributed diffusely in both lobes of the liver
  • Measurable disease

    • At least 1 measurable lesion ≥ 20 mm
  • No evidence of extrahepatic metastases by physical examination or x-ray
  • No previously resected extrahepatic metastases

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Hemoglobin ≥ 9 g/dL
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3

Hepatic

  • AST ≤ 3 times upper limit of normal (ULN)
  • Bilirubin ≤ ULN
  • No preexisting chronic hepatic disease (e.g., chronic active hepatitis, cirrhosis) that would preclude surgical resection of metastases

Renal

  • Creatinine ≤ 1.5 times ULN

Cardiovascular

  • No myocardial infarction within the past 6 months
  • No clinical evidence of congestive heart failure
  • No New York Heart Association class III-IV heart disease
  • No significant cardiac disease
  • No uncontrolled hypertension
  • No unstable angina
  • No congestive heart failure
  • No uncontrolled arrhythmias

Gastrointestinal

  • Adequate oral nutrition with estimated caloric intake of ≥ 1,500 calories/day
  • No severe anorexia or frequent nausea and/or vomiting
  • No history of gastrointestinal bleeding that has not been appropriately addressed

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Able to tolerate major surgery
  • No prior allergic reaction or known sensitivity to chimerized or murine monoclonal antibody therapy
  • No documented presence of human anti-mouse antibodies
  • No known allergy to other platinum compounds
  • No other malignancy within the past 5 years except basal cell or squamous cell skin cancer, carcinoma in situ, or tumors associated with less than 10% probability of death within 5 years of diagnosis
  • No preexisting neuropathy ≥ grade 2
  • No symptomatic pulmonary fibrosis or interstitial pneumonitis
  • No uncontrolled bacterial or viral infection
  • HIV negative
  • No fungal infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No colony-stimulating factors within 24 hours of day 1 of each course
  • No concurrent immunotherapy

Chemotherapy

  • At least 1 year since prior adjuvant systemic fluorouracil with or without levamisole or with or without leucovorin calcium
  • No prior oxaliplatin
  • No prior systemic chemotherapy for metastatic disease
  • No prior chemoembolization for metastatic disease
  • No prior hepatic artery infusion chemotherapy for metastatic disease
  • No other concurrent chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • At least 12 months since prior adjuvant radiotherapy
  • Prior radiofrequency ablation allowed
  • No prior radiotherapy to the liver
  • No prior radiotherapy to more than 25% of the bone marrow
  • No concurrent radiotherapy

Surgery

  • See Disease Characteristics
  • More than 21 days since prior abdominal exploration (with or without intestinal resection)

Other

  • No prior anti-EGFR-directed therapy
  • Prior cryotherapy allowed
  • No oral cryotherapy on day 1 of each course
  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: NCT00056030

  Show 162 Study Locations
Sponsors and Collaborators
North Central Cancer Treatment Group
Investigators
Study Chair: Steven R. Alberts, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Jan C. Buckner, North Central Cancer Treatment Group
ClinicalTrials.gov Identifier: NCT00056030     History of Changes
Other Study ID Numbers: CDR0000271923, NCCTG-N014A
Study First Received: March 6, 2003
Last Updated: June 17, 2012
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
liver metastases
stage IV colon cancer
stage IV rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum

Additional relevant MeSH terms:
Colorectal Neoplasms
Adenocarcinoma
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplastic Processes
Pathologic Processes
Oxaliplatin
Cetuximab
Fluorouracil
Levoleucovorin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on October 01, 2014