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Testing the Addition of Total Ablative Therapy to Usual Systemic Therapy Treatment for Limited Metastatic Colorectal Cancer, The ERASur Study

NCT05673148 · Alliance for Clinical Trials in Oncology
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Official title
A Pragmatic Randomized Phase III Trial Evaluating Total Ablative Therapy for Patients With Limited Metastatic Colorectal Cancer: Evaluating Radiation, Ablation, and Surgery (ERASur)
About this study
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.
Eligibility criteria
Inclusion Criteria: * PRE-REGISTRATION (STEP 0): Histologically-confirmed metastatic colorectal adenocarcinoma * PRE-REGISTRATION (STEP 0): No known microsatellite instable (MSI) tumor * PRE-REGISTRATION (STEP 0): No known BRAF V600E mutation * PRE-REGISTRATION (STEP 0): Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. No known peritoneal and/or omental metastases. If radiologic studies suggest the presence of peritoneal disease, a diagnostic laparoscopy is recommended to verify the absence of peritoneal implants * PRE-REGISTRATION (STEP 0): Primary tumor is already resected OR primary tumor is surgically amenable to resection, as determined by consultation and documentation with surgeon or documentation of discussion in the institutional multi-disciplinary tumor board where a surgeon confirms resectability. Patients with unresectable primary tumors are not eligible * PRE-REGISTRATION (STEP 0): Four (4) or fewer apparent sites of metastatic disease based on review by local medical team of baseline radiographic imaging obtained prior to initiation of systemic therapy. * Sites of metastatic disease must be radiographically evident, but pathologic confirmation is not required. * Liver-only metastatic disease is NOT permitted. For patients with liver metastases, there must be at least one other site of metastasis in addition to the liver to be eligible for this study. * Metastatic lesions must be amenable to any combination of surgical resection, microwave ablation, and/or stereotactic ablative body radiation therapy (SABR). SABR is required for at least one lesion. Therefore, the patient must be seen by a radiation oncologist in consultation to verify eligibility. * Single sites include: * Each hemiliver (right and left), each lobe of the lungs, each adrenal gland, lymph nodes amenable to a single resection or treatment in a single SABR field, bone metastases amenable to treatment in a single SABR field * PRE-REGISTRATION (STEP 0): Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 * PRE-REGISTRATION (STEP 0): A maximum of 16 weeks (4 months) of systemic therapy may be administered prior to pre-registration * REGISTRATION (STEP 1): Patients must have no overt evidence of disease progression during systemic therapy prior to registration * REGISTRATION (STEP 1): Not eligible for hepatic artery infusion pump (HAIP) therapy or benefit of HAIP therapy is undefined * REGISTRATION (STEP 1): Patients must have measurable disease per RECIST v1.1 * REGISTRATION (STEP 1): Patients must be receiving (or have received) first-line systemic therapy for metastatic disease for a minimum of 16 weeks (4 months) and a maximum of 24 weeks (6 months) * REGISTRATION (STEP 1): Prior definitive therapy, including adjuvant chemotherapy, must have been completed at least 12 months prior to diagnosis of metastatic disease * REGISTRATION (STEP 1): Not pregnant and not nursing, because this study involves an agent or treatment that has known genotoxic, mutagenic, and teratogenic effects. \* Therefore, for women of childbearing potential only, a negative pregnancy test done =\< 14 days prior to registration is required * REGISTRATION (STEP 1): Age \>= 18 years * REGISTRATION (STEP 1): Eastern Cooperative Oncology Group (ECOG) performance status: 0-2 * REGISTRATION (STEP 1): Absolute neutrophil count (ANC) \>= 1,500/mm\^3 * REGISTRATION (STEP 1): Platelet count \>= 50,000/mm\^3 * REGISTRATION (STEP 1): Creatinine =\< 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance \>= 30 mL/min \* Calculated using the Cockcroft-Gault equation * REGISTRATION (STEP 1): Total bilirubin =\< 1.5 x ULN * REGISTRATION (STEP 1): Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\]) / alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x ULN \* In the event of metastatic liver disease, =\< 5 x ULN * REGISTRATION (STEP 1): Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Note: HIV testing is not required for eligibility * REGISTRATION (STEP 1): No other planned concurrent investigational agents while on study Exclusion Criteria: * N/A
Study design
Enrollment target: 364 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2023-10-09
Estimated completion: 2032-08-12
Last updated: 2026-04-07
Interventions
Procedure: Stereotactic Ablative RadiotherapyProcedure: ResectionProcedure: Microwave AblationDrug: ChemotherapyProcedure: Computed TomographyProcedure: Magnetic Resonance ImagingProcedure: Positron Emission Tomography
Primary outcomes
  • Overall Survival (OS) (From the date of randomization to the date of death due to all causes, assessed up to 5 years)
Sponsor
Alliance for Clinical Trials in Oncology · other
With: National Cancer Institute (NCI)
Contacts & investigators
ContactEric D. Miller, MD, PhD · contact · eric.miller@osumc.edu · 614-685-4922
All locations (183)
Kingman Regional Medical CenterRecruiting
Kingman, Arizona, United States
Mayo Clinic Hospital in ArizonaRecruiting
Phoenix, Arizona, United States
Tower Cancer Research FoundationRecruiting
Beverly Hills, California, United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory CareRecruiting
Irvine, California, United States
Cedars Sinai Medical CenterRecruiting
Los Angeles, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer CenterRecruiting
Orange, California, United States
University of California Davis Comprehensive Cancer CenterActive Not Recruiting
Sacramento, California, United States
Beebe Medical CenterRecruiting
Lewes, Delaware, United States
Beebe South Coastal Health CampusRecruiting
Millville, Delaware, United States
Helen F Graham Cancer CenterRecruiting
Newark, Delaware, United States
Medical Oncology Hematology Consultants PARecruiting
Newark, Delaware, United States
Christiana Care Health System-Christiana HospitalRecruiting
Newark, Delaware, United States
Beebe Health CampusRecruiting
Rehoboth Beach, Delaware, United States
Christiana Care Health System-Wilmington HospitalRecruiting
Wilmington, Delaware, United States
Sibley Memorial HospitalActive Not Recruiting
Washington D.C., District of Columbia, United States
George Washington University Medical CenterRecruiting
Washington D.C., District of Columbia, United States
UM Sylvester Comprehensive Cancer Center at Coral GablesRecruiting
Coral Gables, Florida, United States
UM Sylvester Comprehensive Cancer Center at Coral SpringsRecruiting
Coral Springs, Florida, United States
UM Sylvester Comprehensive Cancer Center at Deerfield BeachRecruiting
Deerfield Beach, Florida, United States
UM Sylvester Comprehensive Cancer Center at DoralRecruiting
Doral, Florida, United States
UF Health Cancer Institute - GainesvilleRecruiting
Gainesville, Florida, United States
UM Sylvester Comprehensive Cancer Center at HollywoodRecruiting
Hollywood, Florida, United States
Jupiter Medical CenterActive Not Recruiting
Jupiter, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer CenterRecruiting
Miami, Florida, United States
Miami Cancer InstituteActive Not Recruiting
Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at KendallRecruiting
Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at PlantationRecruiting
Plantation, Florida, United States
Grady Health SystemRecruiting
Atlanta, Georgia, United States
Emory Proton Therapy CenterRecruiting
Atlanta, Georgia, United States
Emory University Hospital MidtownRecruiting
Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer InstituteRecruiting
Atlanta, Georgia, United States
Emory Saint Joseph's HospitalRecruiting
Atlanta, Georgia, United States
Saint Luke's Cancer Institute - BoiseRecruiting
Boise, Idaho, United States
Saint Luke's Cancer Institute - FruitlandRecruiting
Fruitland, Idaho, United States
Saint Luke's Cancer Institute - MeridianRecruiting
Meridian, Idaho, United States
Saint Luke's Cancer Institute - NampaRecruiting
Nampa, Idaho, United States
Saint Luke's Cancer Institute - Twin FallsRecruiting
Twin Falls, Idaho, United States
University of IllinoisRecruiting
Chicago, Illinois, United States
UI Health Care Mission Cancer and Blood - Ankeny ClinicRecruiting
Ankeny, Iowa, United States
University of Iowa Healthcare Cancer Services Quad CitiesRecruiting
Bettendorf, Iowa, United States
Mercy Cancer Center-West LakesRecruiting
Clive, Iowa, United States
UI Health Care Mission Cancer and Blood - West Des Moines ClinicRecruiting
Clive, Iowa, United States
Greater Regional Medical CenterRecruiting
Creston, Iowa, United States
Iowa Methodist Medical CenterRecruiting
Des Moines, Iowa, United States
UI Health Care Mission Cancer and Blood - Des Moines ClinicRecruiting
Des Moines, Iowa, United States
Mercy Medical Center - Des MoinesRecruiting
Des Moines, Iowa, United States
UI Health Care Mission Cancer and Blood - Laurel ClinicRecruiting
Des Moines, Iowa, United States
University of Iowa/Holden Comprehensive Cancer CenterRecruiting
Iowa City, Iowa, United States
UI Health Care Mission Cancer and Blood - Waukee ClinicRecruiting
Waukee, Iowa, United States
Mercy Medical Center-West LakesRecruiting
West Des Moines, Iowa, United States
University of Kentucky/Markey Cancer CenterActive Not Recruiting
Lexington, Kentucky, United States
Baptist Health LouisvilleRecruiting
Louisville, Kentucky, United States
University Medical Center New OrleansRecruiting
New Orleans, Louisiana, United States
Johns Hopkins University/Sidney Kimmel Cancer CenterActive Not Recruiting
Baltimore, Maryland, United States
Boston Medical CenterRecruiting
Boston, Massachusetts, United States
Trinity Health Saint Joseph Mercy Hospital Ann ArborRecruiting
Ann Arbor, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - BrightonRecruiting
Brighton, Michigan, United States
Trinity Health Medical Center - BrightonRecruiting
Brighton, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - CantonRecruiting
Canton, Michigan, United States
Trinity Health Medical Center - CantonRecruiting
Canton, Michigan, United States
Chelsea HospitalRecruiting
Chelsea, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea HospitalRecruiting
Chelsea, Michigan, United States
Henry Ford Macomb Hospital-Clinton TownshipActive Not Recruiting
Clinton Township, Michigan, United States
Corewell Health Dearborn HospitalRecruiting
Dearborn, Michigan, United States
Henry Ford HospitalRecruiting
Detroit, Michigan, United States
Corewell Health Farmington Hills HospitalRecruiting
Farmington Hills, Michigan, United States
Genesys Hurley Cancer InstituteRecruiting
Flint, Michigan, United States
Hurley Medical CenterRecruiting
Flint, Michigan, United States
Allegiance HealthActive Not Recruiting
Jackson, Michigan, United States
University of Michigan Health - Sparrow LansingRecruiting
Lansing, Michigan, United States
Trinity Health Saint Mary Mercy Livonia HospitalRecruiting
Livonia, Michigan, United States
Henry Ford Health Providence Novi HospitalRecruiting
Novi, Michigan, United States
Corewell Health William Beaumont University HospitalRecruiting
Royal Oak, Michigan, United States
Henry Ford Health Providence Southfield HospitalRecruiting
Southfield, Michigan, United States
Corewell Health Beaumont Troy HospitalRecruiting
Troy, Michigan, United States
Henry Ford West Bloomfield HospitalActive Not Recruiting
West Bloomfield, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor CampusRecruiting
Ypsilanti, Michigan, United States
Sanford Joe Lueken Cancer CenterRecruiting
Bemidji, Minnesota, United States
Regions HospitalRecruiting
Saint Paul, Minnesota, United States
Baptist Memorial Hospital and Cancer Center-Golden TriangleRecruiting
Columbus, Mississippi, United States
Baptist Cancer Center-GrenadaRecruiting
Grenada, Mississippi, United States
Baptist Memorial Hospital and Cancer Center-Union CountyRecruiting
New Albany, Mississippi, United States
Baptist Memorial Hospital and Cancer Center-OxfordRecruiting
Oxford, Mississippi, United States
Baptist Memorial Hospital and Cancer Center-DesotoRecruiting
Southhaven, Mississippi, United States
MU Health - University Hospital/Ellis Fischel Cancer CenterRecruiting
Columbia, Missouri, United States
Parkland Health Center - FarmingtonRecruiting
Farmington, Missouri, United States
Heartland Regional Medical CenterRecruiting
Saint Joseph, Missouri, United States
Sainte Genevieve County Memorial HospitalRecruiting
Sainte Genevieve, Missouri, United States
Mercy Hospital SpringfieldRecruiting
Springfield, Missouri, United States
Mercy Hospital SouthRecruiting
St Louis, Missouri, United States
Missouri Baptist Medical CenterRecruiting
St Louis, Missouri, United States
Mercy Hospital Saint LouisRecruiting
St Louis, Missouri, United States
Missouri Baptist Sullivan HospitalRecruiting
Sullivan, Missouri, United States
BJC Outpatient Center at Sunset HillsRecruiting
Sunset Hills, Missouri, United States
Billings Clinic Cancer CenterRecruiting
Billings, Montana, United States
Benefis Sletten Cancer InstituteRecruiting
Great Falls, Montana, United States
Nebraska Medicine-BellevueRecruiting
Bellevue, Nebraska, United States
Nebraska Medicine-Village PointeRecruiting
Omaha, Nebraska, United States
University of Nebraska Medical CenterRecruiting
Omaha, Nebraska, United States
Renown Regional Medical CenterRecruiting
Reno, Nevada, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer CenterRecruiting
Lebanon, New Hampshire, United States
Memorial Sloan Kettering Basking RidgeRecruiting
Basking Ridge, New Jersey, United States
Memorial Sloan Kettering MonmouthRecruiting
Middletown, New Jersey, United States
Memorial Sloan Kettering BergenRecruiting
Montvale, New Jersey, United States
University of New Mexico Cancer CenterRecruiting
Albuquerque, New Mexico, United States
New York-Presbyterian/Brooklyn Methodist HospitalRecruiting
Brooklyn, New York, United States
Memorial Sloan Kettering CommackRecruiting
Commack, New York, United States
The New York Hospital Medical Center of QueensRecruiting
Flushing, New York, United States
Northwell Health Physicians Partners Radiation Medicine at QueensRecruiting
Forest Hills, New York, United States
Northwell Health Cancer Institute at HuntingtonRecruiting
Greenlawn, New York, United States
Memorial Sloan Kettering WestchesterRecruiting
Harrison, New York, United States
Northwell Health/Center for Advanced MedicineRecruiting
Lake Success, New York, United States
Northern Westchester HospitalRecruiting
Mount Kisco, New York, United States
Mount Sinai WestRecruiting
New York, New York, United States
Mount Sinai HospitalRecruiting
New York, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer CenterActive Not Recruiting
New York, New York, United States
Manhattan Eye Ear and Throat HospitalRecruiting
New York, New York, United States
Memorial Sloan Kettering Cancer CenterRecruiting
New York, New York, United States
NYP/Weill Cornell Medical CenterRecruiting
New York, New York, United States
Lenox Hill HospitalRecruiting
New York, New York, United States
Queens Cancer CenterRecruiting
Rego Park, New York, United States
University of RochesterActive Not Recruiting
Rochester, New York, United States
Phelps Memorial Hospital CenterRecruiting
Sleepy Hollow, New York, United States
Memorial Sloan Kettering NassauRecruiting
Uniondale, New York, United States
Westchester Medical CenterRecruiting
Valhalla, New York, United States
Wilmot Cancer Institute at WebsterActive Not Recruiting
Webster, New York, United States
Carolinas Medical Center/Levine Cancer InstituteRecruiting
Charlotte, North Carolina, United States
Atrium Health Cabarrus/LCI-ConcordRecruiting
Concord, North Carolina, United States
East Carolina UniversityRecruiting
Greenville, North Carolina, United States
Sanford Bismarck Medical CenterRecruiting
Bismarck, North Dakota, United States
Sanford Broadway Medical CenterRecruiting
Fargo, North Dakota, United States
Sanford Roger Maris Cancer CenterRecruiting
Fargo, North Dakota, United States
Dayton Physicians LLC-Miami Valley SouthActive Not Recruiting
Centerville, Ohio, United States
Miami Valley Hospital SouthRecruiting
Centerville, Ohio, United States
MetroHealth Medical CenterActive Not Recruiting
Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer CenterRecruiting
Columbus, Ohio, United States
Miami Valley HospitalRecruiting
Dayton, Ohio, United States
Premier Blood and Cancer CenterRecruiting
Dayton, Ohio, United States
Dayton Physician LLC - EnglewoodActive Not Recruiting
Dayton, Ohio, United States
Miami Valley Hospital NorthRecruiting
Dayton, Ohio, United States
Atrium Medical Center-Middletown Regional HospitalRecruiting
Franklin, Ohio, United States
Dayton Physicians LLC-AtriumActive Not Recruiting
Franklin, Ohio, United States
Miami Valley Cancer Care and InfusionRecruiting
Greenville, Ohio, United States
Upper Valley Medical CenterRecruiting
Troy, Ohio, United States
University of Oklahoma Health Sciences CenterActive Not Recruiting
Oklahoma City, Oklahoma, United States
Oregon Health and Science UniversityRecruiting
Portland, Oregon, United States
Christiana Care Health System-Concord Health CenterRecruiting
Chadds Ford, Pennsylvania, United States
Geisinger Medical CenterRecruiting
Danville, Pennsylvania, United States
Penn State Milton S Hershey Medical CenterRecruiting
Hershey, Pennsylvania, United States
Lancaster General Ann B Barshinger Cancer InstituteActive Not Recruiting
Lancaster, Pennsylvania, United States
Geisinger Medical Oncology-LewisburgRecruiting
Lewisburg, Pennsylvania, United States
Allegheny General HospitalRecruiting
Pittsburgh, Pennsylvania, United States
West Penn HospitalRecruiting
Pittsburgh, Pennsylvania, United States
Geisinger Wyoming Valley/Henry Cancer CenterRecruiting
Wilkes-Barre, Pennsylvania, United States
Sanford Cancer Center Oncology ClinicRecruiting
Sioux Falls, South Dakota, United States
Sanford USD Medical Center - Sioux FallsRecruiting
Sioux Falls, South Dakota, United States
Baptist Memorial Hospital and Cancer Center-MemphisRecruiting
Memphis, Tennessee, United States
Vanderbilt University/Ingram Cancer CenterRecruiting
Nashville, Tennessee, United States
University of Texas Health Science Center at San AntonioWithdrawn
San Antonio, Texas, United States
Huntsman Cancer Institute/University of UtahRecruiting
Salt Lake City, Utah, United States
Bon Secours Memorial Regional Medical CenterRecruiting
Mechanicsville, Virginia, United States
Bon Secours Saint Francis Medical CenterRecruiting
Midlothian, Virginia, United States
Bon Secours Saint Mary's HospitalRecruiting
Richmond, Virginia, United States
Bon Secours Cancer Institute at Reynolds CrossingRecruiting
Richmond, Virginia, United States
Valley Medical CenterRecruiting
Renton, Washington, United States
Edwards Comprehensive Cancer CenterRecruiting
Huntington, West Virginia, United States
Langlade Hospital and Cancer CenterRecruiting
Antigo, Wisconsin, United States
Ascension Saint Elizabeth HospitalRecruiting
Appleton, Wisconsin, United States
Ascension Southeast Wisconsin Hospital - Elmbrook CampusRecruiting
Brookfield, Wisconsin, United States
Ascension Calumet HospitalRecruiting
Chilton, Wisconsin, United States
Ascension Southeast Wisconsin Hospital - FranklinRecruiting
Franklin, Wisconsin, United States
Ascension Columbia Saint Mary's Hospital OzaukeeRecruiting
Mequon, Wisconsin, United States
Ascension Southeast Wisconsin Hospital - Saint Joseph CampusRecruiting
Milwaukee, Wisconsin, United States
Ascension Columbia Saint Mary's Hospital - MilwaukeeRecruiting
Milwaukee, Wisconsin, United States
Medical College of WisconsinRecruiting
Milwaukee, Wisconsin, United States
Ascension Mercy HospitalRecruiting
Oshkosh, Wisconsin, United States
Ascension All Saints HospitalRecruiting
Racine, Wisconsin, United States
Aspirus Cancer Care - James Beck Cancer CenterRecruiting
Rhinelander, Wisconsin, United States
Aspirus Cancer Care - Stevens PointRecruiting
Stevens Point, Wisconsin, United States
Aspirus Regional Cancer CenterRecruiting
Wausau, Wisconsin, United States
Ascension Medical Group Southeast Wisconsin - Mayfair RoadRecruiting
Wauwatosa, Wisconsin, United States
Aspirus Cancer Care - Wisconsin RapidsRecruiting
Wisconsin Rapids, Wisconsin, United States
Arthur J E Child Comprehensive Cancer CentreRecruiting
Calgary, Alberta, Canada