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

Liver Metastases Clinical Trial

Official title:

A Multi-Institutional Phase II Trial Of Neoadjuvant Capecitabine (XELODA) And Oxaliplatin (ELOXATIN) For Resectable Colorectal Metastases In The Liver

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00070265
• Other study ID #: NCI-2012-02722
• Secondary ID: MDA-ID-02636N01C
• Status: Terminated
• Phase: Phase 2
• First received: October 3, 2003
• Last updated: January 23, 2013
• Start date: August 2003

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 80
• Est. primary completion date: September 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Metastases
• Liver Neoplasms
• Neoplasm Metastasis
• Rectal Neoplasms
• Recurrent Colon Cancer
• Recurrent Rectal Cancer
• Stage IV Colon Cancer
• Stage IV Rectal Cancer

Intervention

Drug:
• oxaliplatin
Given IV
• capecitabine
Given orally

Procedure:
• therapeutic conventional surgery
Undergo surgical resection

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	University of Texas	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of complete resection (R0 resection)	The design of Thall and Simon will be used.	Up to 5 years	No
Secondary	Response rate assessed using RECIST criteria		Up to 5 years	No
Secondary	Resectability in the subsets defined as resectable preoperatively		Up to 5 years	No
Secondary	Improvement in survival associated with downstaging based on metastatic colorectal prognostic score		Up to 5 years	No
Secondary	Disease-free survival		Up to 5 years	No
Secondary	Overall survival		Up to 5 years	No
Secondary	Positron emission tomography response rate		Up to 5 years	No