Neoadjuvant and Adjuvant Capecitabine and Oxaliplatin in Treating Patients With Resectable Liver Metastases Secondary to Colorectal Cancer

This study has been terminated.
(Administratively complete.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00070265
First received: October 3, 2003
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

Drugs used in chemotherapy, such as capecitabine and oxaliplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Giving capecitabine and oxaliplatin before surgery may shrink the tumor so that it can be removed. Giving capecitabine and oxaliplatin after surgery may kill any remaining tumor cells. This phase II trial is studying how well capecitabine and oxaliplatin work when given before and after surgery in treating patients with resectable liver metastases that is secondary to colorectal cancer


Condition Intervention Phase
Liver Metastases
Recurrent Colon Cancer
Recurrent Rectal Cancer
Stage IV Colon Cancer
Stage IV Rectal Cancer
Drug: oxaliplatin
Drug: capecitabine
Procedure: therapeutic conventional surgery
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-Institutional Phase II Trial Of Neoadjuvant Capecitabine (XELODA) And Oxaliplatin (ELOXATIN) For Resectable Colorectal Metastases In The Liver

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Rate of complete resection (R0 resection) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The design of Thall and Simon will be used.


Secondary Outcome Measures:
  • Response rate assessed using RECIST criteria [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Resectability in the subsets defined as resectable preoperatively [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Improvement in survival associated with downstaging based on metastatic colorectal prognostic score [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Disease-free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Positron emission tomography response rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Enrollment: 80
Study Start Date: August 2003
Primary Completion Date: September 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (oxaliplatin, capecitabine, and surgery)

Neoadjuvant chemotherapy: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Surgery: Four to six weeks after the completion of chemotherapy, patients undergo surgical resection of the tumor.

Adjuvant chemotherapy: Patients with satisfactory response to therapy receive 4 additional courses of oxaliplatin and capecitabine after surgery.

Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: capecitabine
Given orally
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda
Procedure: therapeutic conventional surgery
Undergo surgical resection
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the efficacy and toxicity of neoadjuvant and adjuvant capecitabine and oxaliplatin in patients with resectable liver metastases secondary to colorectal cancer who are undergoing surgery.

II. Determine the rates of R0 resection in patients treated with this regimen before surgery.

SECONDARY OBJECTIVES:

I. Determine the response rate in patients treated with this regimen. II. Determine the resectability in the subsets of patients defined as resectable preoperatively and treated with this regimen.

III. Determine improvement in survival associated with downstaging based on metastatic colorectal prognostic score in patients treated with this regimen.

IV. Determine the disease-free and overall survival of patients treated with this regimen.

V. Correlate drug-specific biomarkers with clinical response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Neoadjuvant chemotherapy: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Surgery: Four to six weeks after the completion of chemotherapy, patients undergo surgical resection of the tumor.

Adjuvant chemotherapy: Patients with satisfactory response to therapy receive 4 additional courses of oxaliplatin and capecitabine after surgery.

Patients are followed at 4-6 weeks after surgery, every 3 months for 2 years, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 80 patients will be accrued for this study.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed hepatic colorectal metastasis by percutaneous hepatic biopsy

    • Imaging evidence of liver metastasis by CT helical scan
  • Resectable disease, as determined by a surgeon with hepatic surgery expertise (at least 10 resections performed per year)

    • Resectable, defined as a sparing of 2 adjacent liver segments with adequate vascular inflow and outflow and hepatic remnant volume
    • Minor resections (less than a hemihepatectomy) or major resections (hemihepatectomy or extended hepatectomy) allowed
    • Bilobar resection allowed, including atypical resections
  • No evidence of extrahepatic disease by chest x-ray or CT scan of the chest, abdomen, and pelvis
  • Performance status - Zubrod 0-1
  • WBC at least 3,000/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 9.0 g/dL
  • Bilirubin no greater than 2 mg/dL
  • AST and ALT no greater than 300 IU/L
  • No preexisting chronic hepatic disease (e.g., chronic active hepatitis or cirrhosis) that would preclude surgical resection of metastases
  • Creatinine no greater than 1.5 mg/dL
  • Creatinine clearance 60 mL/min
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other malignancy within the past 5 years except completely resected nonmelanoma skin cancer or carcinoma in situ of the cervix
  • No preexisting grade 2 or greater peripheral neuropathy
  • No concurrent uncontrolled illness
  • No ongoing or active infection
  • No psychiatric illness or social situation that would preclude study compliance
  • No concurrent biologic therapy
  • No concurrent sargramostim (GM-CSF)
  • More than 6 months since prior adjuvant fluorouracil-based chemotherapy
  • No prior chemotherapy for liver metastasis
  • No prior oxaliplatin for colorectal cancer
  • No prior or concurrent hepatic artery infusion chemotherapy for metastatic disease
  • No prior or concurrent radiotherapy for metastatic disease
  • No prior or concurrent radiofrequency ablation for metastatic disease
  • No prior or concurrent cryotherapy/other ablative techniques for metastatic disease
  • No other concurrent investigational therapy
  • No concurrent oral anticoagulation
  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: NCT00070265

Locations
United States, Texas
University of Texas
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Jean-Nicolas Vauthey M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00070265     History of Changes
Other Study ID Numbers: NCI-2012-02722, MDA-ID-02636, N01CM17003, CDR0000331853
Study First Received: October 3, 2003
Last Updated: January 23, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasm Metastasis
Rectal Neoplasms
Colonic Neoplasms
Liver Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Liver Diseases
Capecitabine
Fluorouracil
Oxaliplatin
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 September 18, 2014