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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

Primary Purpose

Colorectal Cancer, Metastatic Cancer

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
capecitabine
floxuridine
oxaliplatin
Sponsored by
NSABP Foundation Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring liver metastases, stage IV colon cancer, stage IV rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cancer Care Center at John Muir Health - Concord Campus
  • City of Hope Comprehensive Cancer Center
  • Veterans Affairs Medical Center - Loma Linda (Pettis)
  • Kaiser Permanente Medical Center - Walnut Creek
  • John Muir/Mt. Diablo Comprehensive Cancer Center
  • CCOP - Christiana Care Health Services
  • Washington Cancer Institute at Washington Hospital Center
  • Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
  • Via Christi Cancer Center at Via Christi Regional Medical Center
  • Central Baptist Hospital
  • Louisville Oncology at Norton Cancer Center
  • CCOP - Ochsner
  • Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center
  • Saint Joseph Mercy Cancer Center
  • Borgess Medical Center
  • West Michigan Cancer Center
  • Bronson Methodist Hospital
  • Mayo Clinic Cancer Center
  • Wake Forest University Comprehensive Cancer Center
  • Altru Cancer Center at Altru Hospital
  • Natalie Warren Bryant Cancer Center at St. Francis Hospital
  • Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center
  • CCOP - Columbia River Oncology Program
  • Providence St. Vincent Medical Center
  • St. Luke's Cancer Network at St. Luke's Hospital
  • Geisinger Medical Center
  • UMC Southwest Cancer and Research Center
  • Fletcher Allen Health Care - University Health Center Campus
  • Virginia Oncology Associates - Hampton
  • Mary Babb Randolph Cancer Center at West Virginia University Hospitals
  • University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm 1: Capecitabine + Oxaliplatin

Arm 2: Floxuridine + Oxaliplatin + Capecitabine

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Progression-free Interval (PFI)
Time to first recurrence of colon cancer at any site

Secondary Outcome Measures

Liver PFI as Measured by Time to Hepatic Progression.
Survival as Measured by Time to Death From Any Cause.
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

Full Information

First Posted
December 20, 2005
Last Updated
May 10, 2013
Sponsor
NSABP Foundation Inc
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00268463
Brief 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
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2013
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated due to low accrual.
Study Start Date
January 2006 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
June 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NSABP Foundation Inc
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Metastatic Cancer
Keywords
liver metastases, stage IV colon cancer, stage IV rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: Capecitabine + Oxaliplatin
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Arm 2: Floxuridine + Oxaliplatin + Capecitabine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
floxuridine
Other Intervention Name(s)
FUDR
Intervention Description
Continuous hepatic arterial infusion of floxuridine 0.2 mg/kg on days 1-14 every 42 days for 4 cycles
Intervention Type
Drug
Intervention Name(s)
oxaliplatin
Other Intervention Name(s)
Eloxatin
Intervention Description
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
Primary Outcome Measure Information:
Title
Progression-free Interval (PFI)
Description
Time to first recurrence of colon cancer at any site
Time Frame
Time from randomization through year 5
Secondary Outcome Measure Information:
Title
Liver PFI as Measured by Time to Hepatic Progression.
Time Frame
Time from randomization through year 5
Title
Survival as Measured by Time to Death From Any Cause.
Time Frame
Time from randomization through year 5
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Norman Wolmark, MD
Organizational Affiliation
NSABP Foundation Inc
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cancer Care Center at John Muir Health - Concord Campus
City
Concord
State/Province
California
ZIP/Postal Code
94524-4110
Country
United States
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010-3000
Country
United States
Facility Name
Veterans Affairs Medical Center - Loma Linda (Pettis)
City
Loma Linda
State/Province
California
ZIP/Postal Code
92357
Country
United States
Facility Name
Kaiser Permanente Medical Center - Walnut Creek
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94596
Country
United States
Facility Name
John Muir/Mt. Diablo Comprehensive Cancer Center
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Facility Name
CCOP - Christiana Care Health Services
City
Newark
State/Province
Delaware
ZIP/Postal Code
19713
Country
United States
Facility Name
Washington Cancer Institute at Washington Hospital Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
City
Savannah
State/Province
Georgia
ZIP/Postal Code
31403-3089
Country
United States
Facility Name
Via Christi Cancer Center at Via Christi Regional Medical Center
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
Central Baptist Hospital
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40503-9985
Country
United States
Facility Name
Louisville Oncology at Norton Cancer Center
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
CCOP - Ochsner
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21237
Country
United States
Facility Name
Saint Joseph Mercy Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48106-0995
Country
United States
Facility Name
Borgess Medical Center
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49001
Country
United States
Facility Name
West Michigan Cancer Center
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49007-3731
Country
United States
Facility Name
Bronson Methodist Hospital
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49007
Country
United States
Facility Name
Mayo Clinic Cancer Center
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Wake Forest University Comprehensive Cancer Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157-1096
Country
United States
Facility Name
Altru Cancer Center at Altru Hospital
City
Grand Forks
State/Province
North Dakota
ZIP/Postal Code
58201
Country
United States
Facility Name
Natalie Warren Bryant Cancer Center at St. Francis Hospital
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74136
Country
United States
Facility Name
Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97210
Country
United States
Facility Name
CCOP - Columbia River Oncology Program
City
Portland
State/Province
Oregon
ZIP/Postal Code
97225
Country
United States
Facility Name
Providence St. Vincent Medical Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97225
Country
United States
Facility Name
St. Luke's Cancer Network at St. Luke's Hospital
City
Bethlehem
State/Province
Pennsylvania
ZIP/Postal Code
18015
Country
United States
Facility Name
Geisinger Medical Center
City
Danville
State/Province
Pennsylvania
ZIP/Postal Code
17822-0001
Country
United States
Facility Name
UMC Southwest Cancer and Research Center
City
Lubbock
State/Province
Texas
ZIP/Postal Code
79415-3364
Country
United States
Facility Name
Fletcher Allen Health Care - University Health Center Campus
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
Facility Name
Virginia Oncology Associates - Hampton
City
Hampton
State/Province
Virginia
ZIP/Postal Code
23666
Country
United States
Facility Name
Mary Babb Randolph Cancer Center at West Virginia University Hospitals
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Facility Name
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792-6164
Country
United States

12. IPD Sharing Statement

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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

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