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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

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

Conditions
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Liver Metastases, Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IV Colon Cancer, Stage IV Rectal Cancer

Intervention / Treatment
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* Drug: oxaliplatin
* Drug: capecitabine
* Procedure: therapeutic conventional surgery
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (oxaliplatin, capecitabine, and surgery)<br>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<br>* Given IV<br>* Other names: L-OHP;Drug: capecitabine<br>* Given orally<br>* Other names: Xeloda;Procedure: therapeutic conventional surgery<br>* Undergo surgical resection<br>Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of complete resection (R0 resection) | The design of Thall and Simon will be used. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate assessed using RECIST criteria |  | Up to 5 years | 
| Resectability in the subsets defined as resectable preoperatively |  | Up to 5 years | 
| Improvement in survival associated with downstaging based on metastatic colorectal prognostic score |  | Up to 5 years | 
| Disease-free survival |  | Up to 5 years | 
| Overall survival |  | Up to 5 years | 
| Positron emission tomography response rate |  | Up to 5 years |