Phase III Randomized Study of Adjuvant Therapy Comprising Oxaliplatin and Capecitabine With Versus Without Hepatic Arterial Infusion of Floxuridine in Patients Undergoing Surgical Resection and/or Ablation for Hepatic Metastases From Colorectal Cancer
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
Phase III - Treatment Trial
Active Trial - 18 and over
NCI
NSABP-C-09
NCT00268463
Special Category: CTSU trial
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 Objective
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 Objective
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 histiologic 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 receiving hepatic arterial infusion of floxuridine.
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.
Expected Enrollment
400 total
A total of 400 patients will be accrued for this study.
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 pump and catheter placement.
Arm I (oxaliplatin and capecitabine): Within 8 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 8 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.
After completion of study treatment, patients are followed periodically for 5 years.
Trial Contact Information and Trial Lead Organizations
National Surgical Adjuvant Breast and Bowel Project
Lawrence Wagman, MD, Protocol chair Ph: 626-359-8111
Email: becomingapatient@coh.org
Trial Sites
U.S.A.
• California
o Concord
Cancer Care Center at John Muir Health - Concord Campus
Cancer Clinical Trials Ph: 925-674-2580
o Duarte
City of Hope Comprehensive Cancer Center
Clinical Trials Office - New Patient Services Ph: 800-826-4673
Email: becomingapatient@coh.org
o Loma Linda
Veterans Affairs Medical Center - Loma Linda (Pettis)
Mark Reeves, MD, PhD Ph: 909-825-7084
o Walnut Creek
John Muir/Mt. Diablo Comprehensive Cancer Center
Cancer Clinical Trials Ph: 925-941-4246
Kaiser Permanente Medical Center - Walnut Creek
Louis Fehrenbacher, MD Ph: 707-651-2577
• Connecticut
o Bridgeport
Bridgeport Hospital
Clinical Trials Office - Bridgeport Hospital Ph: 203-384-3193
• Delaware
o Newark
CCOP - Christiana Care Health Services
Clinical Trial Office - CCOP - Christiana Care Health Services Ph: 302-733-6227
• District of Columbia
o Washington
Washington Cancer Institute at Washington Hospital Center
Clinical Trials Office - Washington Cancer Institute Ph: 202-877-8839
• Georgia
o Savannah
Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center . Clinical Trials Office - Curtis & Elizabeth Anderson Cancer Institute Ph: 912-350-8568
• Kansas
o Wichita
Via Christi Cancer Center at Via Christi Regional Medical Center
Shaker Dakhil, MD, FACP Ph: 316-262-4467
• Kentucky
o Lexington
Central Baptist Hospital
Clinical Trials Office - Central Baptist Hospital Ph: 859-260-6425
o Louisville
Louisville Oncology at Norton Cancer Center
Clinical Trials Office - Louisville Oncology Ph: 502-629-2500
• Louisiana
o New Orleans
CCOP - Ochsner
Carl Kardinal, MD Ph: 504-842-3910
o Maryland
Baltimore
Harry and Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center
John Zapas, MD Ph: 443-777-7911
o Towson
Cancer Institute at St. Joseph Medical Center
Mark Fraiman Ph: 410-337-1000
• Michigan
o Ann Arbor
Saint Joseph Mercy Cancer Center
Philip Stella, MD Ph: 734-712-5658
888-474-4673
o Kalamazoo
Bronson Methodist Hospital
Raymond Lord, MD Ph: 269-373-7488
West Michigan Cancer Center
Clinical Trials Office - West Michigan Cancer Center Ph: 269-373-7458
Borgess Medical Center
Raymond Lord, MD Ph: 269-373-7488
o Lansing
Breslin Cancer Center at Ingham Regional Medical Center
Clinical Trials Office - Breslin Cancer Center Ph: 517-367-5070
• North Carolina
o Winston-Salem
Wake Forest University Comprehensive Cancer Center
Clinical Trials Office - Wake Forest University Comprehensive Cancer Center Ph: 336-713-6771
• North Dakota
o Grand Forks
Altru Cancer Center at Altru Hospital
Clinical Trails Office - Altru Cancer Center Ph: 701-780-6520
• Oklahoma
o Tulsa
Natalie Warren Bryant Cancer Center at St. Francis Hospital
James Lockhart, MD Ph: 918-481-4800
• Oregon
o Portland
CCOP - Columbia River Oncology Program
Keith Lanier, MD Ph: 503-216-6260
Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center
Clinical Trials Office - Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center Ph: 503-413-1742
Providence St. Vincent Medical Center
Clinical Trials Office - Providence St. Vincent Medical Center Ph: 503-215-6412
• Pennsylvania
o Bethlehem
St. Luke's Hospital Cancer Center
Alan Morrison, MD Ph: 610-954-3580
o Danville
Geisinger Medical Center
Clinical Trials Office - Geisinger Medical Center Ph: 570-271-5251
• Texas
o Lubbock
UMC Southwest Cancer and Research Center
Clinical Trials Office - UMC Southwest Cancer and Research Center Ph: 806-775-8590
• Wisconsin
o Madison
University of Wisconsin Comprehensive Cancer Center
Clinical Trials Office - University of Wisconsin Comprehensive Cancer Center Ph: 608-262-5223