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

May 10, 2013 updated by: NSABP Foundation Inc

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

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, capecitabine, and floxuridine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Hepatic arterial infusion uses a catheter to carry tumor-killing substances, such as chemotherapy, directly into the liver. Giving chemotherapy in different ways may kill more tumor cells. It is not yet known whether giving oxaliplatin and capecitabine together with an hepatic arterial infusion with floxuridine is more effective than giving oxaliplatin and capecitabine alone in treating patients who are undergoing surgery and/or ablation for liver metastases due to colorectal cancer.

PURPOSE: This randomized phase III trial is studying oxaliplatin, capecitabine, and an hepatic arterial infusion with floxuridine to see how well they work compared to oxaliplatin and capecitabine in treating patients who are undergoing surgery and/or ablation for liver metastases due to colorectal cancer.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • 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

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

Tertiary

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

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 1 (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 2 (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.

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

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Concord, California, United States, 94524-4110
        • Cancer Care Center at John Muir Health - Concord Campus
      • Duarte, California, United States, 91010-3000
        • City of Hope Comprehensive Cancer Center
      • Loma Linda, California, United States, 92357
        • Veterans Affairs Medical Center - Loma Linda (Pettis)
      • Walnut Creek, California, United States, 94596
        • Kaiser Permanente Medical Center - Walnut Creek
      • Walnut Creek, California, United States, 94598
        • John Muir/Mt. Diablo Comprehensive Cancer Center
    • Delaware
      • Newark, Delaware, United States, 19713
        • CCOP - Christiana Care Health Services
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Washington Cancer Institute at Washington Hospital Center
    • Georgia
      • Savannah, Georgia, United States, 31403-3089
        • Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
    • Kansas
      • Wichita, Kansas, United States, 67214
        • Via Christi Cancer Center at Via Christi Regional Medical Center
    • Kentucky
      • Lexington, Kentucky, United States, 40503-9985
        • Central Baptist Hospital
      • Louisville, Kentucky, United States, 40202
        • Louisville Oncology at Norton Cancer Center
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • CCOP - Ochsner
    • Maryland
      • Baltimore, Maryland, United States, 21237
        • Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48106-0995
        • Saint Joseph Mercy Cancer Center
      • Kalamazoo, Michigan, United States, 49007
        • Bronson Methodist Hospital
      • Kalamazoo, Michigan, United States, 49001
        • Borgess Medical Center
      • Kalamazoo, Michigan, United States, 49007-3731
        • West Michigan Cancer Center
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Cancer Center
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157-1096
        • Wake Forest University Comprehensive Cancer Center
    • North Dakota
      • Grand Forks, North Dakota, United States, 58201
        • Altru Cancer Center at Altru Hospital
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74136
        • Natalie Warren Bryant Cancer Center at St. Francis Hospital
    • Oregon
      • Portland, Oregon, United States, 97225
        • CCOP - Columbia River Oncology Program
      • Portland, Oregon, United States, 97225
        • Providence St. Vincent Medical Center
      • Portland, Oregon, United States, 97210
        • Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center
    • Pennsylvania
      • Bethlehem, Pennsylvania, United States, 18015
        • St. Luke's Cancer Network at St. Luke's Hospital
      • Danville, Pennsylvania, United States, 17822-0001
        • Geisinger Medical Center
    • Texas
      • Lubbock, Texas, United States, 79415-3364
        • UMC Southwest Cancer and Research Center
    • Vermont
      • Burlington, Vermont, United States, 05401
        • Fletcher Allen Health Care - University Health Center Campus
    • Virginia
      • Hampton, Virginia, United States, 23666
        • Virginia Oncology Associates - Hampton
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • Mary Babb Randolph Cancer Center at West Virginia University Hospitals
    • Wisconsin
      • Madison, Wisconsin, United States, 53792-6164
        • University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

PATIENT CHARACTERISTICS:

  • Life expectancy ≥ 5 years, excluding their colorectal cancer
  • Eastern Cooperative Oncology Group (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/mm^3
  • Platelet count ≥ 100,000/mm^3
  • PT/international normalized ratio (INR) ≤ 1.5 unless patient is on therapeutic doses of anticoagulant medication
  • Total bilirubin ≤ upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 2.5 ULN
  • aspartate aminotransferase (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

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm 1: Capecitabine + Oxaliplatin
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 cycles in the absence of disease progression or unacceptable toxicity.
Drug: capecitabine

Oral capecitabine 850 mg/m2 twice daily on days 1-14 every 21 days for 8 cycles: Arm 1

Oral capecitabine 850 mg/m2 twice daily on days 22-35 every 42 days for 4 cycles and then on days 1-14 every 21 days for 4 cycles: Arm 2

Other Names:
  • Xeloda
Drug: oxaliplatin

Oxaliplatin 130 mg/m2 IV over 2 hours on day 1 every 21 days for 8 cycles: Arm 1

Oxaliplatin 130 mg/m2 IV over 2 hours on day 22 every 42 days for 4 cycles and then on day 1 every 21 days for 4 cycles: Arm 2

Other Names:
  • Eloxatin
Experimental: Arm 2: Floxuridine + Oxaliplatin + Capecitabine
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 cycles in the absence of unacceptable toxicity. Beginning with cycle 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 cycles.
Drug: capecitabine

Oral capecitabine 850 mg/m2 twice daily on days 1-14 every 21 days for 8 cycles: Arm 1

Oral capecitabine 850 mg/m2 twice daily on days 22-35 every 42 days for 4 cycles and then on days 1-14 every 21 days for 4 cycles: Arm 2

Other Names:
  • Xeloda
Drug: oxaliplatin

Oxaliplatin 130 mg/m2 IV over 2 hours on day 1 every 21 days for 8 cycles: Arm 1

Oxaliplatin 130 mg/m2 IV over 2 hours on day 22 every 42 days for 4 cycles and then on day 1 every 21 days for 4 cycles: Arm 2

Other Names:
  • Eloxatin
Drug: floxuridine
Continuous hepatic arterial infusion of floxuridine 0.2 mg/kg on days 1-14 every 42 days for 4 cycles
Other Names:
  • FUDR

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Interval (PFI)
Time Frame: Time from randomization through year 5
Time to first recurrence of colon cancer at any site
Time from randomization through year 5

Secondary Outcome Measures

Outcome Measure
Time Frame
Liver PFI as Measured by Time to Hepatic Progression.
Time Frame: Time from randomization through year 5
Time from randomization through year 5
Survival as Measured by Time to Death From Any Cause.
Time Frame: Time from randomization through year 5
Time from randomization through year 5
Scales Specific to Social/Family, Emotional, and Functional Well-being, Perceived Convenience of Care, and Self-reported Symptoms
Time Frame: Prior to randomization, 4-6 weeks after surgery, 18 weeks after starting chemotherapy and after completion of chemotherapy
Prior to randomization, 4-6 weeks after surgery, 18 weeks after starting chemotherapy and after completion of chemotherapy
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
Time Frame: Prior to randomization, 4-6 weeks after surgery, 18 weeks after the start of chemotherapy and after completion of chemotherapy
Prior to randomization, 4-6 weeks after surgery, 18 weeks after the start of chemotherapy and after completion of chemotherapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NSABP Foundation Inc

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2006

Primary Completion (Actual)

June 1, 2008

Study Completion (Actual)

June 1, 2008

Study Registration Dates

First Submitted

December 20, 2005

First Submitted That Met QC Criteria

December 20, 2005

First Posted (Estimate)

December 22, 2005

Study Record Updates

Last Update Posted (Estimate)

May 15, 2013

Last Update Submitted That Met QC Criteria

May 10, 2013

Last Verified

May 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NSABP C-09
  • U10CA012027 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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