Combination Chemotherapy Before or After Surgery in Treating Patients With Colorectal Cancer With Liver Metastases That Could Be Removed By Surgery

A Phase III Study Evaluating the Role of Perioperative Chemotherapy in Patients With Potentially Resectable Hepatic Colorectal Metastases

RATIONALE: Drugs used in chemotherapy work in different ways to kill tumor cells or stop them from growing. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving combination chemotherapy after surgery may kill any remaining tumor cells. It is not yet known whether giving combination chemotherapy before and after surgery is more effective than giving combination chemotherapy after surgery.

PURPOSE: This randomized phase III trial is studying giving combination chemotherapy before and after surgery to see how well it works compared to giving combination chemotherapy after surgery in treating patients with colorectal cancer with liver metastases that could be removed by surgery.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer; Metastatic Cancer
• Intervention / Treatment: Procedure: Postoperative chemotherapy; Procedure: Perioperative chemotherapy

Detailed Description

OBJECTIVES:

Primary

• To evaluate the difference in recurrence-free survival (RFS) of patients with potentially resectable hepatic colorectal metastases receiving perioperative (preoperative plus postoperative) adjuvant chemotherapy vs only postoperative adjuvant chemotherapy following liver resection for colorectal metastases.

Secondary

• To compare the proportion of patients between study arms who are R0 or R1 resected, alive, and free of recurrence at 6 months.
• To compare RFS between study arms in the cohort of patients event-free at 6 months.
• To compare overall survival between study arms.
• To evaluate the difference in R0 and combined R0 + R1 resection rates in patients receiving neoadjuvant therapy and those undergoing initial surgical resection.
• To compare the postoperative morbidity profile between study arms.
• To evaluate the safety and toxicity profile of postoperative and perioperative administration of chemotherapy and bevacizumab.

Tertiary

• To evaluate the relationship of baseline circulating tumor cells (CTC) to RFS.
• To evaluate the relationship of baseline CTC to R0 resection.
• To evaluate the relationship of pre-resection CTC in the preoperative therapy group only with RFS and R0 resection.

OUTLINE: This is a multicenter study. Patients are stratified by number of liver metastases (1-3 vs 4+), chemotherapy regimen* (mFOLFOX6 vs FOLFIRI), and synchronous** primary colorectal cancer (yes vs no). Patients are randomized to 1 of 2 treatment arms.

NOTE: *Patients who have not received previous oxaliplatin receive mFOLFOX6 chemotherapy comprising oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46 hours on day 1. Patients who have received previous oxaliplatin receive FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46 hours on day 1.

NOTE: **Synchronous is defined as the detection (by imaging) of suspicious liver metastases within 90 days before or after the date of histologic diagnosis of the primary colon or rectal cancer.

• Arm 1 (postoperative): Patients undergo hepatic resection. Beginning 31-56 days after surgery, patients receive mFOLFOX6 or FOLFIRI chemotherapy IV on day 1 over 3 hours. Patients receive an additional dose of fluorouracil over 46 hours using a portable pump. Treatment repeats every 2 weeks for 12 courses.
• Arm 2 (perioperative): Patients receive mFOLFOX6 or FOLFIRI chemotherapy IV over 3 hours on day 1. Patients receive an additional dose of fluorouracil over 46 hours using a portable pump. Treatment repeats for every 2 weeks for 6 courses. Patients then undergo hepatic resection. Beginning 31-56 days after surgery, patients receive an additional 6 courses of mFOLFOX6 or FOLFIRI chemotherapy.

Blood and tumor tissue samples may be collected periodically for correlative studies.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Antioch, California, United States, 94531
      • Kaiser Permanente - Deer Valley
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center
    • Fremont, California, United States, 94538
      • Kaiser Permanente - Fremont
    • Hayward, California, United States, 94545
      • Kaiser Permanente Medical Center - Hayward
    • Oakland, California, United States, 94611
      • Kaiser Permanente Medical Center - Oakland
    • Orange, California, United States, 92868
      • St. Joseph Hospital Regional Cancer Center - Orange
    • Redwood City, California, United States, 94063
      • Kaiser Permanente Medical Center - Redwood City
    • Richmond, California, United States, 94801
      • Kaiser Permanente Medical Center - Richmond
    • Roseville, California, United States, 95661
      • Kaiser Permanente Medical Center - Roseville
    • Sacramento, California, United States, 95823
      • South Sacramento Kaiser-Permanente Medical Center
    • Sacramento, California, United States, 95825
      • Kaiser Permanente Medical Center - Sacramento
    • San Diego, California, United States, 92120
      • Kaiser Permanente Medical Office -Vandever Medical Office
    • San Francisco, California, United States, 94115
      • Kaiser Permanente Medical Center - San Francisco Geary Campus
    • San Jose, California, United States, 95119
      • Kaiser Permanente Medical Center - Santa Teresa
    • San Rafael, California, United States, 94903
      • Kaiser Foundation Hospital - San Rafael
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente Medical Center - Santa Clara Kiely Campus
    • Santa Rosa, California, United States, 95403
      • Kaiser Permanente Medical Center - Santa Rosa
    • South San Francisco, California, United States, 94080
      • Kaiser Permanente Medical Center - South San Francisco
    • Stockton, California, United States, 95210
      • Kaiser Permanente Medical Facility - Stockton
    • Vacaville, California, United States, 95688
      • Kaiser Permanente Medical Center - Vacaville
    • Vallejo, California, United States, 94589
      • Kaiser Permanente Medical Center - Vallejo
    • Walnut Creek, California, United States, 94596
      • Kaiser Permanente Medical Center - Walnut Creek
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center at UC Health Sciences Center
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
    • Manchester, Connecticut, United States, 06040
      • Manchester Memorial Hospital
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Tunnell Cancer Center at Beebe Medical Center
    • 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
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist Cancer Institute - Jacksonville
    • Lakeland, Florida, United States, 33805
      • Lakeland Regional Cancer Center at Lakeland Regional Medical Center
    • Orlando, Florida, United States, 32803-1273
      • Florida Hospital Cancer Institute at Florida Hospital Orlando
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Veterans Affairs Medical Center - Atlanta (Decatur)
  • Hawaii
    • Honolulu, Hawaii, United States, 96819
      • Kaiser Permanente - Moanalua Medical Center and Clinic
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
  • Illinois
    • Bloomington, Illinois, United States, 61701
      • St. Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Graham Hospital
    • Carthage, Illinois, United States, 62321
      • Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital Cancer Care Institute
    • Eureka, Illinois, United States, 61530
      • Eureka Community Hospital
    • Galesburg, Illinois, United States, 61401
      • Galesburg Clinic, PC
    • Havana, Illinois, United States, 62644
      • Mason District Hospital
    • Hinsdale, Illinois, United States, 60521
      • Hinsdale Hematology Oncology Associates
    • Macomb, Illinois, United States, 61455
      • Mcdonough District Hospital
    • Normal, Illinois, United States, 61761
      • Bromenn Regional Medical Center
    • Normal, Illinois, United States, 61761
      • Community Cancer Center
    • Oak Lawn, Illinois, United States, 60453-2699
      • Advocate Christ Medical Center
    • Ottawa, Illinois, United States, 61350
      • Community Hospital of Ottawa
    • Pekin, Illinois, United States, 61554
      • Cancer Treatment Center at Pekin Hospital
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61614
      • Proctor Hospital
    • Peoria, Illinois, United States, 61637
      • OSF St. Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • CCOP - Illinois Oncology Research Association
    • Peoria, Illinois, United States, 61615
      • Oncology Hematology Associates of Central Illinois, PC - Peoria
    • Peru, Illinois, United States, 61354
      • Illinois Valley Community Hospital
    • Princeton, Illinois, United States, 61356
      • Perry Memorial Hospital
    • Springfield, Illinois, United States, 62781-0001
      • Regional Cancer Center at Memorial Medical Center
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • St. Francis Hospital and Health Centers - Beech Grove Campus
    • Elkhart, Indiana, United States, 46514-2098
      • Elkhart Clinic, LLC
    • Kokomo, Indiana, United States, 46904
      • Howard Community Hospital
    • Richmond, Indiana, United States, 47374
      • Reid Hospital & Health Care Services
    • South Bend, Indiana, United States, 46601
      • CCOP - Northern Indiana CR Consortium
    • South Bend, Indiana, United States, 46601
      • Michiana Hematology-Oncology, PC - South Bend
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic, PC
    • Clive, Iowa, United States, 50325
      • Medical Oncology and Hematology Associates - West Des Moines
    • Clive, Iowa, United States, 50325
      • Mercy Cancer Center - West Lakes
    • Des Moines, Iowa, United States, 50309
      • CCOP - Iowa Oncology Research Association
    • Des Moines, Iowa, United States, 50309
      • John Stoddard Cancer Center at Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates at John Stoddard Cancer Center
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates at Mercy Cancer Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Cancer Center at Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50316
      • John Stoddard Cancer Center at Iowa Lutheran Hospital
    • Iowa City, Iowa, United States, 52242-1002
      • Holden Comprehensive Cancer Center at University of Iowa
    • Ottumwa, Iowa, United States, 52501
      • McCreery Cancer Center at Ottumwa Regional
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology-Oncology Associates, LLP
    • Sioux City, Iowa, United States, 51102
      • Mercy Medical Center - Sioux City
    • Sioux City, Iowa, United States, 51104
      • St. Luke's Regional Medical Center
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas, PA - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas, PA - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - El Dorado
    • Fort Scott, Kansas, United States, 66701
      • Cancer Center of Kansas - Fort Scott
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas, PA - Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Liberal, Kansas, United States, 67901
      • Cancer Center of Kansas, PA - Liberal
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas, PA - Newton
    • Overland Park, Kansas, United States, 66209
      • Menorah Medical Center
    • Overland Park, Kansas, United States, 66213
      • Saint Luke's Hospital - South
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas, PA - Parsons
    • Prairie Village, Kansas, United States, 66208
      • CCOP - Kansas City
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas, PA - Pratt
    • Salina, Kansas, United States, 67401
      • Cancer Center of Kansas, PA - Salina
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas, PA - Wellington
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas, PA - Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas, PA - Wichita
    • Wichita, Kansas, United States, 67214
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67214
      • Via Christi Cancer Center at Via Christi Regional Medical Center
    • Wichita, Kansas, United States, 67208
      • Associates in Womens Health, PA - North Review
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas, PA - Winfield
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0093
      • Lucille P. Markey Cancer Center at University of Kentucky
    • Lexington, Kentucky, United States, 40503-9985
      • Central Baptist Hospital
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Ochsner Health Center - Bluebonnet
    • Covington, Louisiana, United States, 70433
      • Ochsner Health Center - Covington
    • New Orleans, Louisiana, United States, 70121
      • CCOP - Ochsner
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney kimmel comprehensive cancer center at johns hopkins
    • Baltimore, Maryland, United States, 21237
      • Harry and Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center
    • Elkton MD, Maryland, United States, 21921
      • Union Hospital of Cecil County
    • Salisbury, Maryland, United States, 21801
      • Peninsula Regional Medical Center
  • Massachusetts
    • Pittsfield, Massachusetts, United States, 01201
      • Berkshire Hematology Oncology, PC
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center at Bixby Medical Center
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Cancer Center
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Michigan Cancer Research Consortium
    • Dearborn, Michigan, United States, 48123-2500
      • Oakwood Cancer Center at Oakwood Hospital and Medical Center
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Van Elslander Cancer Center at St. John Hospital and Medical Center
    • Jackson, Michigan, United States, 49201
      • Foote Memorial Hospital
    • 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
    • Lansing, Michigan, United States, 48912-1811
      • Sparrow Regional Cancer Center
    • Lansing, Michigan, United States, 48910
      • Breslin Cancer Center at Ingham Regional Medical Center
    • Livonia, Michigan, United States, 48154
      • St. Mary Mercy Hospital
    • Monroe, Michigan, United States, 48162
      • Mercy Memorial Hospital - Monroe
    • Pontiac, Michigan, United States, 48341-2985
      • St. Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Mercy Regional Cancer Center at Mercy Hospital
    • Saginaw, Michigan, United States, 48601
      • Seton Cancer Institute at Saint Mary's - Saginaw
    • Saint Joseph, Michigan, United States, 49085
      • Lakeside Cancer Specialists, PLLC
    • Southfield, Michigan, United States, 48075
      • Providence Cancer Institute at Providence Hospital - Southfield Campus
    • Warren, Michigan, United States, 48093
      • St. John Macomb Hospital
  • Minnesota
    • Brainerd, Minnesota, United States, 56401
      • St. Joseph's Medical Center
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy and Unity Cancer Center at Mercy Hospital
    • Duluth, Minnesota, United States, 55805
      • CCOP - Duluth
    • Duluth, Minnesota, United States, 55805
      • St. Luke's Hospital Cancer Care Center
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fergus Falls, Minnesota, United States, 56537
      • Fergus Falls Medical Group, PA
    • Fridley, Minnesota, United States, 55432
      • Mercy and Unity Cancer Center at Unity Hospital
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology, PA - Maplewood
    • Maplewood, Minnesota, United States, 55109
      • HealthEast Cancer Care at St. John's Hospital
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center - Minneapolis
    • Robbinsdale, Minnesota, United States, 55422-2900
      • Humphrey Cancer Center at North Memorial Outpatient Center
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Cancer Center
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Shakopee, Minnesota, United States, 55379
      • St. Francis Cancer Center at St. Francis Medical Center
    • St. Paul, Minnesota, United States, 55101
      • Regions Hospital Cancer Care Center
    • Stillwater, Minnesota, United States, 55082
      • Lakeview Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Willmar, Minnesota, United States, 56201
      • Willmar Cancer Center at Rice Memorial Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology, PA - Woodbury
  • Missouri
    • Jefferson City, Missouri, United States, 65109
      • Goldschmidt Cancer Center
    • Kansas City, Missouri, United States, 64116
      • North Kansas City Hospital
    • Kansas City, Missouri, United States, 64132
      • Research Medical Center
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Cancer Institute at Saint Luke's Hospital
    • Kansas City, Missouri, United States, 64114
      • St. Joseph Medical Center
    • Kansas City, Missouri, United States, 64116
      • Parvin Radiation Oncology
    • Kansas City, Missouri, United States, 64118
      • Heartland Hematology Oncology Associates, Incorporated
    • Lee's Summit, Missouri, United States, 64086
      • Saint Luke's East - Lee's Summit
    • Liberty, Missouri, United States, 64068
      • Liberty Hospital
    • Saint Joseph, Missouri, United States, 64506
      • Heartland Regional Medical Center
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Cancer Center
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University Cancer Center
    • Saint Louis, Missouri, United States, 63141
      • Comprehensive Cancer Care, PC
    • Springfield, Missouri, United States, 65802
      • CCOP - Cancer Research for the Ozarks
    • Springfield, Missouri, United States, 65807
      • Hulston Cancer Center at Cox Medical Center South
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Billings, Montana, United States, 59101
      • St. Vincent Healthcare Cancer Care Services
    • Billings, Montana, United States, 59107-7000
      • Billings Clinic - Downtown
    • Billings, Montana, United States, 59102
      • Hematology-Oncology Centers of the Northern Rockies - Billings
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Cancer Center
    • Butte, Montana, United States, 59701
      • St. James Healthcare Cancer Care
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic - Main Facility
    • Great Falls, Montana, United States, 59405
      • Sletten Cancer Institute at Benefis Healthcare
    • Helena, Montana, United States, 59601
      • St. Peter's Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology, PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology at KRMC
    • Missoula, Montana, United States, 59807
      • Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Cancer Resource Center - Lincoln
    • Omaha, Nebraska, United States, 68106
      • CCOP - Missouri Valley Cancer Consortium
    • Omaha, Nebraska, United States, 68122
      • Immanuel Medical Center
    • Omaha, Nebraska, United States, 68124
      • Alegant Health Cancer Center at Bergan Mercy Medical Center
    • Omaha, Nebraska, United States, 68131-2197
      • Creighton University Medical Center
  • New Jersey
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
    • Voorhees, New Jersey, United States, 08043
      • Cancer Institute of New Jersey at Cooper - Voorhees
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-5636
      • University of New Mexico Cancer Center
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • Glens Falls, New York, United States, 12801
      • Charles R. Wood Cancer Center at Glens Falls Hospital
    • New York, New York, United States, 10016
      • NYU Cancer Institute at New York University Medical Center
    • Staten Island, New York, United States, 10305
      • Nalitt Cancer Institute at Staten Island University Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28233-3549
      • Presbyterian Cancer Center at Presbyterian Hospital
    • Greenville, North Carolina, United States, 27834
      • Leo W. Jenkins Cancer Center at ECU Medical School
    • Kinston, North Carolina, United States, 28501
      • Kinston Medical Specialists
    • Statesville, North Carolina, United States, 28677
      • Iredell Memorial Hospital
    • Winston-Salem, North Carolina, United States, 27157-1096
      • Wake Forest University Comprehensive Cancer Center
    • Winston-Salem, North Carolina, United States, 27103
      • Forsyth Regional Cancer Center at Forsyth Medical Center
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • CCOP - MeritCare Hospital
  • Ohio
    • Bellefontaine, Ohio, United States, 43311
      • Mary Rutan Hospital
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Cleveland, Ohio, United States, 44106-5065
      • Case Comprehensive Cancer Center
    • Columbus, Ohio, United States, 43214-3998
      • Riverside Methodist Hospital Cancer Care
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health - West Hospital
    • Columbus, Ohio, United States, 43215
      • CCOP - Columbus
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center Cancer Care
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital at Ohio Health
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital
    • Dayton, Ohio, United States, 45409
      • David L. Rike Cancer Center at Miami Valley Hospital
    • Dayton, Ohio, United States, 45420
      • CCOP - Dayton
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Elyria, Ohio, United States, 44035
      • Community Cancer Center
    • Elyria, Ohio, United States, 44035
      • Hematology Oncology Center
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Medical Associates
    • Franklin, Ohio, United States, 45005-1066
      • Middletown Regional Hospital
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Kettering, Ohio, United States, 45429
      • Charles F. Kettering Memorial Hospital
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Lima, Ohio, United States, 45804
      • Lima Memorial Hospital
    • Marietta, Ohio, United States, 45750
      • Strecker Cancer Center at Marietta Memorial Hospital
    • Mount Vernon, Ohio, United States, 43050
      • Knox Community Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial Cancer Care Program at Licking Memorial Hospital
    • Norwalk, Ohio, United States, 44857
      • Fisher-Titus Medical Center
    • Oregon, Ohio, United States, 43616
      • St. Charles Mercy Hospital
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care, Incorporated
    • Springfield, Ohio, United States, 45505
      • Community Hospital of Springfield and Clark County
    • Sylvania, Ohio, United States, 43560
      • Flower Hospital Cancer Center
    • Tiffin, Ohio, United States, 44883
      • Mercy Hospital of Tiffin
    • Toledo, Ohio, United States, 43608
      • St. Vincent Mercy Medical Center
    • Toledo, Ohio, United States, 43606
      • Toledo Hospital
    • Toledo, Ohio, United States, 43614
      • Medical University of Ohio Cancer Center
    • Toledo, Ohio, United States, 43617
      • CCOP - Toledo Community Hospital
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic, Incorporated - Main Clinic
    • Toledo, Ohio, United States, 43623
      • St. Anne Mercy Hospital
    • Troy, Ohio, United States, 45373-1300
      • UVMC Cancer Care Center at Upper Valley Medical Center
    • Wauseon, Ohio, United States, 43567
      • Fulton County Health Center
    • Westerville, Ohio, United States, 43081
      • Mount Carmel St. Ann's Cancer Center
    • Xenia, Ohio, United States, 45385
      • Ruth G. McMillan Cancer Center at Greene Memorial Hospital
    • Zanesville, Ohio, United States, 43701
      • Genesis - Good Samaritan Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Cancer Institute
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center at St. Francis Hospital
  • Pennsylvania
    • Butler, Pennsylvania, United States, 16001
      • Butler Memorial Hospital
    • Media, Pennsylvania, United States, 19063
      • Riddle Memorial Hospital Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107-5541
      • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Cancer Centers
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Cancer Center at Allegheny General Hospital
    • Reading, Pennsylvania, United States, 19612-6052
      • McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
    • Upland, Pennsylvania, United States, 19013
      • Associates in Hematology-Oncology, PC at Crozer Regional Cancer Center
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Greenville, South Carolina, United States, 29601
      • Bon Secours St. Francis Health System
    • Greenwood, South Carolina, United States, 29646
      • Self Regional Cancer Center at Self Regional Medical Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Medical X-Ray Center, PC
    • Sioux Falls, South Dakota, United States, 57117-5039
      • Sanford Cancer Center at Sanford USD Medical Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37916
      • Thompson Cancer Survival Center
  • Texas
    • Dallas, Texas, United States, 75235
      • Parkland Memorial Hospital
    • Dallas, Texas, United States, 75390
      • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
    • Lubbock, Texas, United States, 79410-1894
      • Joe Arrington Cancer Research and Treatment Center
  • Utah
    • Cedar City, Utah, United States, 84720
      • Sandra L. Maxwell Cancer Center
    • Logan, Utah, United States, 84321
      • Logan Regional Hospital
    • Ogden, Utah, United States, 84403
      • Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center - Provo
    • Saint George, Utah, United States, 84770
      • Dixie Regional Medical Center - East Campus
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical Center
    • Fredericksburg, Virginia, United States, 22401
      • Fredericksburg Oncology, Incorporated
  • Washington
    • Bellevue, Washington, United States, 98004
      • Overlake Cancer Center at Overlake Hospital Medical Center
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98112
      • Group Health Central Hospital
    • Seattle, Washington, United States, 98122-4307
      • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
  • West Virginia
    • Parkersburg, West Virginia, United States, 26102
      • Community Comprehensive Cancer Center at Camden-Clark Memorial Hospital
  • Wisconsin
    • Chippewa Falls, Wisconsin, United States, 54729
      • Marshfield Clinic - Chippewa Center
    • Eau Claire, Wisconsin, United States, 54701
      • Marshfield Clinic Cancer Care at Regional Cancer Center
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic - Marshfield Center
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Cancer Center
    • Minocqua, Wisconsin, United States, 54548
      • Marshfield Clinic - Lakeland Center
    • Rhinelander, Wisconsin, United States, 54501
      • Ministry Medical Group at Saint Mary's Hospital
    • Rice Lake, Wisconsin, United States, 54868
      • Marshfield Clinic - Indianhead Center
    • Stevens Point, Wisconsin, United States, 54481
      • Marshfield Clinic at Saint Michael's Hospital
    • Weston, Wisconsin, United States, 54476
      • Marshfield Clinic - Weston Center
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Marshfield Clinic - Wisconsin Rapids Center
  • Wyoming
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center at Sheridan Memorial Hospital

Participation Criteria

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 confirmed colorectal adenocarcinoma

  • Hepatic metastasis (no histologic confirmation required) and no evidence of extrahepatic metastatic disease within the past 4 weeks by one of the following imaging studies*:

    • PET/CT scan with contrast
    • PET scan AND CT scan with contrast
    • PET scan AND MRI with contrast
    • PET/CT scan without contrast AND MRI with contrast NOTE: *If findings noted in imaging study reports are equivocal, the determination of whether or not the findings represent extrahepatic disease will be at the investigator's discretion.

  • No history of or concurrent evidence of extrahepatic metastases

    • Patients with regional nodes that are suspicious on imaging and are associated with the primary colorectal tumor are eligible provided the nodes will be resected with the primary tumor after randomization
  • No radiographic evidence of metastases to portal lymph nodes (node > 1 cm in diameter) unless the node(s) are proven by biopsy to be negative
• No anal, small bowel, or appendiceal carcinoma
• No sarcoma, lymphoma, or carcinoid colorectal malignant diseases

• Within 4 weeks before randomization, the liver metastases must be determined by a hepatic surgeon to be resectable based on meeting both of the following criteria:

  • A complete resection can be performed in a single operation
  • There are ≥ 2 uninvolved contiguous segments of the liver

• Meets one of the following criteria:

  • Primary tumor and regional nodes resected with clear surgical margins and no evidence of extrahepatic disease
  • Unresected primary tumor with plans to resect the primary tumor before randomization
  • Unresected primary tumor with plans to resect the primary tumor and the liver metastases in a single surgical procedure performed after randomization
• No unresected primary tumor in the colon or rectum with significant symptoms related to obstruction or that will require radiotherapy

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Life expectancy ≥ 5 years (excluding the diagnosis of metastatic CRC)
• absolute neutrophil count (ANC) ≥ 1,200/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL
• Total bilirubin ≤ upper limit of normal (ULN)
• aspartate aminotransferase (AST) ≤ 5.0 times ULN
• Alkaline phosphatase ≤ 5.0 times ULN
• Serum creatinine ≤ ULN OR calculated creatinine clearance ≥ 30 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 180 days after completion of study treatment
• Considered a potential candidate for a major hepatic surgical procedure
• No grade 3 or 4 anorexia, grade 3 nausea, or vomiting ≥ grade 2 (per CTCAE v4.0) related to metastatic disease
• No paresthesias, peripheral sensory neuropathy, or peripheral motor neuropathy ≥ grade 2 per Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0 (patients with grade 2 neuropathy who will receive FOLFIRI are eligible)
• No uncontrolled high BP defined as systolic BP ≥ 160 mm Hg OR diastolic BP ≥ 100 mm Hg, with or without antihypertensive medication (patients with initial BP elevations are eligible provided initiation or adjustment of BP medication lowers pressure to meet this criteria)
• Documented history of congestive heart failure requiring chronic medical therapy
• No active inflammatory bowel disease
• No active infection or chronic infection requiring chronic suppressive antibiotics
• No known bleeding diathesis or coagulopathy
• No symptomatic interstitial pneumonitis OR definitive evidence of interstitial pneumonitis described on CT scan, MRI, or chest x-ray in asymptomatic patients

• No other malignancies unless the patient is considered to be disease-free and has completed therapy for the malignancy ≥ 1 year ago

  • Patients with carcinoma in situ of the cervix, CRC in situ, melanoma in situ, or basal cell or squamous cell carcinoma of the skin diagnosed and treated at any time before study treatment are eligible
• No known Gilbert syndrome
• Not known to be homozygous for the UGT1A1 allele (for patients who will receive FOLFIRI chemotherapy)
• No prior serious hypersensitivity reaction to any of the agents administered as part of study treatment (determination of "serious" is at the investigator's discretion)
• No other serious concurrent medical condition that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to participate in the study, or cause a delay in the initiation of therapy (surgery or chemotherapy) longer than 4 weeks following randomization
• No psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements
• No pre-existing chronic hepatic disease (e.g., chronic active hepatitis, cirrhosis) that, in the opinion of the investigator and hepatic surgeon, would limit the patient's ability to undergo hepatic metastasectomy

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No previous hepatic-directed therapy, including hepatic resection and/or ablation, hepatic arterial infusion therapy, or hepatic radiotherapy

  • Patients who have only had an incision or excisional biopsy are eligible
• No previous chemotherapy or any other systemic therapy for metastatic colorectal cancer (CRC)
• No prior or concurrent portal vein embolization or other hepatic preconditioning techniques
• At least 30 days since prior investigational products
• No intent to use ablation to treat any hepatic lesion
• No concurrent therapeutic doses of coumadin or equivalent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Postoperative chemotherapy; Patients undergo hepatic resection. Beginning 31-56 days after surgery, patients receive mFOLFOX6 or FOLFIRI chemotherapy IV on day 1 over 3 hours. Patients receive an additional dose of fluorouracil over 46 hours using a portable pump. Treatment repeats every 2 weeks for 12 cycles.	Procedure: Postoperative chemotherapy; Patients undergo hepatic resection. Beginning 31-56 days after surgery, patients receive mFOLFOX6 or FOLFIRI chemotherapy IV on day 1 over 3 hours. Patients receive an additional dose of fluorouracil over 46 hours using a portable pump. Treatment repeats every 2 weeks for 12 cycles.
Experimental: Arm 2: Perioperative chemotherapy; Patients receive mFOLFOX6 or FOLFIRI chemotherapy IV over 3 hours on day 1. Patients receive an additional dose of fluorouracil over 46 hours using a portable pump. Treatment repeats for every 2 weeks for 6 cycles. Patients then undergo hepatic resection. Beginning 31-56 days after surgery, patients receive an additional 6 cycles of mFOLFOX6 or FOLFIRI chemotherapy.	Procedure: Perioperative chemotherapy; Patients receive mFOLFOX6 or FOLFIRI chemotherapy IV over 3 hours on day 1. Patients receive an additional dose of fluorouracil over 46 hours using a portable pump. Treatment repeats for every 2 weeks for 6 cycles. Patients then undergo hepatic resection. Beginning 31-56 days after surgery, patients receive an additional 6 cycles of mFOLFOX6 or FOLFIRI chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free Survival (RFS)	Time to recurrence or death	From study entry until the date of recurrence or death or for a maximum of 5 years.

Secondary Outcome Measures

Outcome Measure	Time Frame
RFS of Patients Event-free	From study entry until the date of recurrence or for a maximum of 6 months.
Overall Survival	From study entry until the time of death or for a maximum of 5 years.
The Difference in R0 and Combined R0 + R1 Resection Rates Between the Two Arms.	Assessed at the time of surgery
Frequencies of Selected Postoperative Surgical Complications and Other Adverse Events Within 30 Days of Surgery	Assessed within 30 days from the time of surgery
Frequencies of Adverse Events as Assessed by the NCI CTCAE v4.0	From study entry through 3 months after the last treatment dose.

Collaborators and Investigators

• Sponsor: NSABP Foundation Inc
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: August 25, 2010
• First Submitted That Met QC Criteria: August 25, 2010
• First Posted (Estimate): August 26, 2010

Study Record Updates

• Last Update Posted (Estimate): May 10, 2013
• Last Update Submitted That Met QC Criteria: May 8, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; stage IV rectal cancer; stage IV colon cancer; adenocarcinoma of the colon; liver metastases
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: NSABP C-11; NSABP-C-11