A Pragmatic Randomized Phase III Trial Evaluating Total Ablative Therapy for Patients With Limited Metastatic Colorectal Cancer: Evaluating Radiation, Ablation, and Surgery (ERASur)
Summary
This phase III trial compares total ablative therapy and usual systemic therapy to usual systemic therapy alone in treating patients with colorectal cancer that has spread to up to 4 body sites (limited metastatic). The usual approach for patients who are not participating in a study is treatment with intravenous (IV) (through a vein) and/or oral medications (systemic therapy) to help stop the cancer sites from getting larger and the spread of the cancer to additional body sites. Ablative means that the intention of the local treatment is to eliminate the cancer at that metastatic site. The ablative local therapy will consist of very focused, intensive radiotherapy called stereotactic ablative radiotherapy (SABR) with or without surgical resection and/or microwave ablation, which is a procedure where a needle is temporarily inserted in the tumor and heat is used to destroy the cancer cells. SABR, surgical resection, and microwave ablation have been tested for safety, but it is not scientifically proven that the addition of these treatments are beneficial for your stage of cancer. The addition of ablative local therapy to all known metastatic sites to the usual approach of systemic therapy could shrink or remove the tumor(s) or prevent the tumor(s) from returning.
Detailed description
PRIMARY OBJECTIVE: I. To evaluate and compare overall survival (OS) (measured from time of randomization) in patients with newly diagnosed oligometastatic colorectal cancer (oCRC) treated with total ablative therapy (TAT) in addition to standard of care (SOC) systemic therapy versus SOC systemic therapy. SECONDARY OBJECTIVES: I. To evaluate and compare event-free survival (EFS) (measured from time of randomization) between the two treatment arms. II. To assess the adverse events (AE) profile within each of the two treatment arms. III. To evaluate the time to local recurrence (TLR) (measured from completion of TAT) in patients with newly diagnosed oCRC treated with TAT + SOC systemic therapy. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients undergo TAT on study, consisting of SABR with or without surgical resection and/or microwave ablation. Patients also receive SOC chemotherapy on study. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) or positron emission tomography (PET)/CT scans throughout the trial. ARM 2: Patients receive SOC chemotherapy on study. Patients also undergo Patients also undergo CT or MRI or PET/CT scans throughout the trial.
Arms & interventions
- ProcedureStereotactic Ablative Radiotherapy
Undergo SABR
- ProcedureResection
undergo surgical resection
- ProcedureMicrowave Ablation
undergo microwave ablation
- DrugChemotherapy
Receive SOC chemotherapy
- ProcedureComputed Tomography
Undergo CT scan
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- ProcedurePositron Emission Tomography
Undergo PET scan
Outcome measures
Primary
Overall Survival (OS)
o Description: The hazard ratio (HR) for OS will be estimated using a stratified Cox proportional hazards model and the 95% confidence interval (CI) for the HR will be provided. The Kaplan-Meier methodology will be used to estimate the median OS for each treatment arm, and Kaplan-Meier curves will be produced. OS will also be compared between treatment arms using the log rank test
Time frame: From the date of randomization to the date of death due to all causes, assessed up to 5 years
Secondary
Event Free Survival (EFS)
Time frame: From randomization to the date of first documented progression, recurrence, or death due to all causes, whichever occurs first, assessed up to 5 years
• Incidence of Adverse Events (AEs), assessed using National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) version 5.0 (v5.0)
Time frame: Up to 5 years
Time to local recurrence (TLR)
Time frame: from the end of TAT to the date of first documented recurrence at any disease site treated with TAT, assessed up to 5 years after randomization
Eligibility criteria
Study locations (184)
Kingman Regional Medical Center
Kingman, Arizona, 86401
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054
Tower Cancer Research Foundation
Beverly Hills, California, 90211
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612
Cedars-Sinai Medical Center
Los Angeles, California, 90048
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Beebe Medical Center
Lewes, Delaware, 19958
Beebe South Coastal Health Campus
Millville, Delaware, 19967
Helen F Graham Cancer Center
Newark, Delaware, 19713
Medical Oncology Hematology Consultants PA
Newark, Delaware, 19713
Christiana Care Health System-Christiana Hospital
Newark, Delaware, 19718
Beebe Health Campus
Rehoboth Beach, Delaware, 19971
Christiana Care Health System-Wilmington Hospital
Wilmington, Delaware, 19801
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016
George Washington University Medical Center
Washington D.C., District of Columbia, 20037
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146
UM Sylvester Comprehensive Cancer Center at Coral Springs
Coral Springs, Florida, 33065
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442
UM Sylvester Comprehensive Cancer Center at Doral
Doral, Florida, 33166
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610
UM Sylvester Comprehensive Cancer Center at Hollywood
Hollywood, Florida, 33021
Jupiter Medical Center
Jupiter, Florida, 33458
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Miami Cancer Institute
Miami, Florida, 33176
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, 33176
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324
Grady Health System
Atlanta, Georgia, 30303
Emory Proton Therapy Center
Atlanta, Georgia, 30308
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, 83619
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, 83642
Saint Luke's Cancer Institute - Nampa
Nampa, Idaho, 83687
Saint Luke's Cancer Institute - Twin Falls
Twin Falls, Idaho, 83301
University of Illinois
Chicago, Illinois, 60612
Baptist Health Floyd
New Albany, Indiana, 47150
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023
University of Iowa Healthcare Cancer Services Quad Cities
Bettendorf, Iowa, 52722
Mercy Cancer Center-West Lakes
Clive, Iowa, 50325
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, 50325
Greater Regional Medical Center
Creston, Iowa, 50801
Iowa Methodist Medical Center
Des Moines, Iowa, 50309
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa, 50263
Mercy Medical Center-West Lakes
West Des Moines, Iowa, 50266
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Baptist Health Louisville
Louisville, Kentucky, 40207
University Medical Center New Orleans
New Orleans, Louisiana, 70112
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Boston Medical Center
Boston, Massachusetts, 02118
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, 48106
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114
Trinity Health Medical Center - Brighton
Brighton, Michigan, 48114
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, 48188
Trinity Health Medical Center - Canton
Canton, Michigan, 48188
Chelsea Hospital
Chelsea, Michigan, 48118
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, 48118
Henry Ford Macomb Hospital-Clinton Township
Clinton Township, Michigan, 48038
Corewell Health Dearborn Hospital
Dearborn, Michigan, 48124
Henry Ford Hospital
Detroit, Michigan, 48202
Corewell Health Farmington Hills Hospital
Farmington Hills, Michigan, 48336
Genesys Hurley Cancer Institute
Flint, Michigan, 48503
Hurley Medical Center
Flint, Michigan, 48503
Allegiance Health
Jackson, Michigan, 49201
University of Michigan Health - Sparrow Lansing
Lansing, Michigan, 48912
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, 48154
Henry Ford Health Providence Novi Hospital
Novi, Michigan, 48374
Corewell Health William Beaumont University Hospital
Royal Oak, Michigan, 48073
Henry Ford Health Providence Southfield Hospital
Southfield, Michigan, 48075
Corewell Health Beaumont Troy Hospital
Troy, Michigan, 48085
Henry Ford West Bloomfield Hospital
West Bloomfield, Michigan, 48322
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, 48197
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota, 56601
Regions Hospital
Saint Paul, Minnesota, 55101
Baptist Memorial Hospital and Cancer Center-Golden Triangle
Columbus, Mississippi, 39705
Baptist Cancer Center-Grenada
Grenada, Mississippi, 38901
Baptist Memorial Hospital and Cancer Center-Union County
New Albany, Mississippi, 38652
Baptist Memorial Hospital and Cancer Center-Oxford
Oxford, Mississippi, 38655
Baptist Memorial Hospital and Cancer Center-Desoto
Southhaven, Mississippi, 38671
MU Health - University Hospital/Ellis Fischel Cancer Center
Columbia, Missouri, 65212
Parkland Health Center - Farmington
Farmington, Missouri, 63640
Heartland Regional Medical Center
Saint Joseph, Missouri, 64506
Sainte Genevieve County Memorial Hospital
Sainte Genevieve, Missouri, 63670
Mercy Hospital Springfield
Springfield, Missouri, 65804
Mercy Hospital South
St Louis, Missouri, 63128
Missouri Baptist Medical Center
St Louis, Missouri, 63131
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
Missouri Baptist Sullivan Hospital
Sullivan, Missouri, 63080
BJC Outpatient Center at Sunset Hills
Sunset Hills, Missouri, 63127
Billings Clinic Cancer Center
Billings, Montana, 59101
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405
Nebraska Medicine-Bellevue
Bellevue, Nebraska, 68123
Nebraska Medicine-Village Pointe
Omaha, Nebraska, 68118
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Renown Regional Medical Center
Reno, Nevada, 89502
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920
Englewood Hospital and Medical Center
Englewood, New Jersey, 07631
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
New York-Presbyterian/Brooklyn Methodist Hospital
Brooklyn, New York, 11215
Memorial Sloan Kettering Commack
Commack, New York, 11725
The New York Hospital Medical Center of Queens
Flushing, New York, 11355
Northwell Health Physicians Partners Radiation Medicine at Queens
Forest Hills, New York, 11375
Northwell Health Cancer Institute at Huntington
Greenlawn, New York, 11740
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Northwell Health/Center for Advanced Medicine
Lake Success, New York, 11042
Northern Westchester Hospital
Mount Kisco, New York, 10549
Mount Sinai West
New York, New York, 10019
Mount Sinai Hospital
New York, New York, 10029
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Manhattan Eye Ear and Throat Hospital
New York, New York, 10065
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
NYP/Weill Cornell Medical Center
New York, New York, 10065
Lenox Hill Hospital
New York, New York, 10075
Queens Cancer Center
Rego Park, New York, 11374
University of Rochester
Rochester, New York, 14642
Phelps Memorial Hospital Center
Sleepy Hollow, New York, 10591
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553
Westchester Medical Center
Valhalla, New York, 10595
Wilmot Cancer Institute at Webster
Webster, New York, 14580
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Atrium Health Cabarrus/LCI-Concord
Concord, North Carolina, 28025
East Carolina University
Greenville, North Carolina, 27834
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122
Dayton Physicians LLC-Miami Valley South
Centerville, Ohio, 45459
Miami Valley Hospital South
Centerville, Ohio, 45459
MetroHealth Medical Center
Cleveland, Ohio, 44109
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Miami Valley Hospital
Dayton, Ohio, 45409
Premier Blood and Cancer Center
Dayton, Ohio, 45409
Dayton Physician LLC - Englewood
Dayton, Ohio, 45415
Miami Valley Hospital North
Dayton, Ohio, 45415
Atrium Medical Center-Middletown Regional Hospital
Franklin, Ohio, 45005-1066
Dayton Physicians LLC-Atrium
Franklin, Ohio, 45005
Miami Valley Cancer Care and Infusion
Greenville, Ohio, 45331
Upper Valley Medical Center
Troy, Ohio, 45373
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Oregon Health and Science University
Portland, Oregon, 97239
Christiana Care Health System-Concord Health Center
Chadds Ford, Pennsylvania, 19317
Geisinger Medical Center
Danville, Pennsylvania, 17822
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850
Lancaster General Ann B Barshinger Cancer Institute
Lancaster, Pennsylvania, 17601
Geisinger Medical Oncology-Lewisburg
Lewisburg, Pennsylvania, 17837
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
West Penn Hospital
Pittsburgh, Pennsylvania, 15224
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania, 18711
Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota, 57104
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134
Baptist Memorial Hospital and Cancer Center-Memphis
Memphis, Tennessee, 38120
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
Bon Secours Memorial Regional Medical Center
Mechanicsville, Virginia, 23116
Bon Secours Saint Francis Medical Center
Midlothian, Virginia, 23114
Bon Secours Saint Mary's Hospital
Richmond, Virginia, 23226
Bon Secours Cancer Institute at Reynolds Crossing
Richmond, Virginia, 23230
Valley Medical Center
Renton, Washington, 98055
Edwards Comprehensive Cancer Center
Huntington, West Virginia, 25701
Langlade Hospital and Cancer Center
Antigo, Wisconsin, 54409
Ascension Saint Elizabeth Hospital
Appleton, Wisconsin, 54915
Ascension Southeast Wisconsin Hospital - Elmbrook Campus
Brookfield, Wisconsin, 53045
Ascension Calumet Hospital
Chilton, Wisconsin, 53014
Ascension Southeast Wisconsin Hospital - Franklin
Franklin, Wisconsin, 53132
Ascension Columbia Saint Mary's Hospital Ozaukee
Mequon, Wisconsin, 53097
Ascension Southeast Wisconsin Hospital - Saint Joseph Campus
Milwaukee, Wisconsin, 53210
Ascension Columbia Saint Mary's Hospital - Milwaukee
Milwaukee, Wisconsin, 53211
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Ascension Mercy Hospital
Oshkosh, Wisconsin, 54904
Ascension All Saints Hospital
Racine, Wisconsin, 53405
Aspirus Cancer Care - James Beck Cancer Center
Rhinelander, Wisconsin, 54501
Aspirus Cancer Care - Stevens Point
Stevens Point, Wisconsin, 54481
Aspirus Regional Cancer Center
Wausau, Wisconsin, 54401
Ascension Medical Group Southeast Wisconsin - Mayfair Road
Wauwatosa, Wisconsin, 53226
Aspirus Cancer Care - Wisconsin Rapids
Wisconsin Rapids, Wisconsin, 54494
References
- Hitchcock KE, Miller ED, Shi Q, Dixon JG, Gholami S, White SB, Wu C, Goulet CC, George M, Jee KW, Wright CL, Yaeger R, Shergill A, Hong TS, George TJ, O'Reilly EM, Meyerhardt JA, Romesser PB. Alliance for clinical trials in Oncology (Alliance) trial A022101/NRG-GI009: a pragmatic randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer: evaluating radiation, ablation, and surgery (ERASur). BMC Cancer. 2024 Feb 13;24(1):201. doi: 10.1186/s12885-024-11899-2.(PubMed)
- Miller ED, Hitchcock KE, Romesser PB. Oligometastatic Colorectal Cancer: A Review of Definitions and Patient Selection for Local Therapies. J Gastrointest Cancer. 2023 Dec;54(4):1116-1127. doi: 10.1007/s12029-022-00900-5. Epub 2023 Jan 18.(PubMed)