Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Oxaliplatin and Capecitabine With or Without an Hepatic Arterial Infusion With Floxuridine in Treating Patients Who Are Undergoing Surgery and/or Ablation for Liver Metastases Due to Colorectal Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Completed	18 and over	NCI	NSABP-C-09 NCT00268463

Special Category: NCI Web site featured trial, CTSU trial

Objectives

Primary

1. Compare progression-free interval (PFI) in patients undergoing surgical resection and/or ablation for hepatic metastases from colorectal cancer treated with adjuvant therapy comprising oxaliplatin and capecitabine with vs without hepatic arterial infusion of floxuridine.

Secondary

1. Compare overall survival and liver PFI between the two treatment groups.
2. Assess toxicity in each of the treatment regimens.
3. Compare self-reported symptoms between two treatment groups.
4. Compare quality of life in each of the treatment regimens.

Tertiary

1. Examine the prognostic worth, in terms of PFI, of specific molecular markers in hepatic metastases.

Entry Criteria

Disease Characteristics:

• Histologically* or cytologically confirmed colorectal adenocarcinoma
  • No other cellular type (e.g., sarcoma, lymphoma, or carcinoid)

   [Note: *If the primary colorectal tumor and the hepatic lesions have been identified at the same time and it is not possible to biopsy the colorectal lesion, the patient will be eligible without histologic confirmation of the colorectal primary cancer as long as other radiographic studies or scans document the characteristics of a colorectal cancer]

• Synchronous or metachronous metastatic disease confined to the liver
  • No more than 6 hepatic metastatic lesions that can potentially be resected or ablated
  • For patients presenting with synchronous lesion(s) in the colon and/or rectum, the primary tumors must, in the opinion of the investigator, appear to be completely resectable
• Must be able to undergo surgery and/or ablation within 28 days following randomization
• No evidence of extrahepatic metastases
• No prior colorectal metastases
• No recurrent colorectal cancer concurrent with hepatic metastases

Prior/Concurrent Therapy:

• Prior adjuvant fluorouracil alone or in combination with levamisole, leucovorin calcium, irinotecan hydrochloride, or oxaliplatin allowed if these regimens were completed > 6 months ago
• No prior resection/ablation, hepatic arterial infusion therapy, or any systemic chemotherapy for metastatic disease
  • Prior excisional biopsy allowed
• No prior radiotherapy to the liver
• No concurrent bevacizumab in patients who have had pump/catheter placement receiving hepatic arterial infusion of floxuridine
  • Patients who meet specific situations outlined in the protocol and who have not had pump placement may receive bevacizumab at the physician's discretion
• No concurrent halogenated antiviral agents such as sorivudine or brivudine in patients receiving fluorouracil, floxuridine, or capecitabine
• No concurrent filgrastim (G-CSF), pegfilgrastim, or sargramostim (GM-CSF) as primary prophylaxis for neutropenia
  • Following neutropenic events, these drugs may be used at the physician's discretion during subsequent cycles
• No other concurrent cancer therapy
• No other concurrent investigational agents

Patient Characteristics:

• Life expectancy ≥ 5 years, excluding their colorectal cancer
• ECOG (Zubrod) performance status 0-1
• No other malignancy within the past 5 years except carcinoma in situ of the cervix, melanoma in situ, basal cell or squamous cell skin cancer, or carcinoma of the colon or rectum
• Absolute granulocyte count ≥ 1,200/mm³
• Platelet count ≥ 100,000/mm³
• PT/INR ≤ 1.5 unless patient is on therapeutic doses of anticoagulant medication
• Total bilirubin ≤ upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2.5 ULN
• AST ≤ 2.5 times ULN
• Calculated creatinine clearance > 50 mL/min
• Not pregnant or lactating
• Negative pregnancy test
• Patients with child bearing potential must agree to use adequate contraception
• Able to swallow oral medication
• No preexisting chronic hepatic disease (e.g., chronic active hepatitis or cirrhosis)
• No grade 3 or 4 anorexia or nausea
• No vomiting ≥ grade 2
• No clinically significant peripheral neuropathy defined as ≥ grade 2 neurosensory or neuromotor toxicity
• No psychiatric or addictive disorders or other condition that, in the opinion of the investigator, would preclude study participation

Expected Enrollment

A total of 400 patients will be accrued for this study.

Outcomes

Progression-free interval (PFI)

Liver PFI
Survival
Scales specific to social/family, emotional, and functional well-being, perceived convenience of care, and self-reported symptoms
Quality of life as measured by the Functional Assessment of Cancer Therapy Trial Outcome Index at baseline, at 4-6 weeks following surgery (before initiation of chemotherapy), and periodically during study

Outline

This is a randomized study. Patients are stratified according to intended surgical technique (surgical resection alone vs cryoablation or radiofrequency ablation [RFA] alone vs combination of resection and ablation) and prior adjuvant chemotherapy regimen (chemotherapy with vs without oxaliplatin vs no chemotherapy). Patients are randomized to 1 of 2 treatment arms.

All patients undergo surgical resection and/or hepatic cryoablation or RFA to remove a maximum of 6 colorectal hepatic metastases. Patients randomized to arm II also undergo intra-arterial catheter and if applicable, pump placement.

• Arm I (oxaliplatin and capecitabine): Within 4-6 weeks after surgery and/or ablation, 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 8 courses in the absence of disease progression or unacceptable toxicity.
• Arm II (oxaliplatin, capecitabine, and hepatic arterial infusion of floxuridine): Within 4-6 weeks after surgery and/or ablation, patients receive a continuous hepatic arterial infusion of floxuridine on days 1-14, oxaliplatin IV over 2 hours on day 22, and oral capecitabine twice daily on days 22-35. Treatment repeats every 42 days for 4 courses in the absence of unacceptable toxicity. Beginning with course 5, patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Treatment with oxaliplatin and capecitabine repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, 4-6 weeks after surgery or ablation, approximately 18 weeks after beginning of chemotherapy, and 4-6 weeks after beginning the last cycle of chemotherapy.

After completion of study treatment, patients are followed periodically.

Trial Contact Information

Trial Lead Organizations

National Surgical Adjuvant Breast and Bowel Project

Lawrence Wagman, MD, Protocol chair		Ph: 626-359-8111 Email: becomingapatient@coh.org

Related Information

Featured trial article

Registry Information
Official Title		A Phase III Clinical Trial Comparing Oxaliplatin, Capecitabine and Hepatic Arterial Infusion of Floxuridine to Oxaliplatin and Capecitabine in Patients with Resected or Ablated Liver Metastases from Colorectal Cancer
Trial Start Date		2006-01-13
Trial Completion Date		2008-06-12
Registered in ClinicalTrials.gov		NCT00268463
Date Submitted to PDQ		2005-10-12
Information Last Verified		2008-10-27

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