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NCT05673148PHASE3Recruiting

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

Alliance for Clinical Trials in Oncology

Start Date

10/9/2023

Completion Date

8/12/2032

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

PROCEDURE

Stereotactic Ablative Radiotherapy

PROCEDURE

Resection

PROCEDURE

Microwave Ablation

DRUG

Chemotherapy

PROCEDURE

Computed Tomography

PROCEDURE

Magnetic Resonance Imaging

PROCEDURE

Positron Emission Tomography

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Conditions

Metastatic Colorectal AdenocarcinomaStage IV Colorectal Cancer AJCC v8

Locations

Kingman Regional Medical Center

Kingman, Arizona 86401

United States

Mayo Clinic Hospital in Arizona

Phoenix, Arizona 85054

United States

Tower Cancer Research Foundation

Beverly Hills, California 90211

United States

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California 92612

United States

Cedars-Sinai Medical Center

Los Angeles, California 90048

United States

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California 92868

United States

University of California Davis Comprehensive Cancer Center

Sacramento, California 95817

United States

Beebe Medical Center

Lewes, Delaware 19958

United States

Beebe South Coastal Health Campus

Millville, Delaware 19967

United States

Helen F Graham Cancer Center

Newark, Delaware 19713

United States

Medical Oncology Hematology Consultants PA

Newark, Delaware 19713

United States

Christiana Care Health System-Christiana Hospital

Newark, Delaware 19718

United States

Beebe Health Campus

Rehoboth Beach, Delaware 19971

United States

Christiana Care Health System-Wilmington Hospital

Wilmington, Delaware 19801

United States

Sibley Memorial Hospital

Washington D.C., District of Columbia 20016

United States

George Washington University Medical Center

Washington D.C., District of Columbia 20037

United States

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida 33146

United States

UM Sylvester Comprehensive Cancer Center at Coral Springs

Coral Springs, Florida 33065

United States

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida 33442

United States

UM Sylvester Comprehensive Cancer Center at Doral

Doral, Florida 33166

United States

UF Health Cancer Institute - Gainesville

Gainesville, Florida 32610

United States

UM Sylvester Comprehensive Cancer Center at Hollywood

Hollywood, Florida 33021

United States

Jupiter Medical Center

Jupiter, Florida 33458

United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida 33136

United States

Miami Cancer Institute

Miami, Florida 33176

United States

UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida 33176

United States

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida 33324

United States

Grady Health System

Atlanta, Georgia 30303

United States

Emory Proton Therapy Center

Atlanta, Georgia 30308

United States

Emory University Hospital Midtown

Atlanta, Georgia 30308

United States

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia 30322

United States

Emory Saint Joseph's Hospital

Atlanta, Georgia 30342

United States

Saint Luke's Cancer Institute - Boise

Boise, Idaho 83712

United States

Saint Luke's Cancer Institute - Fruitland

Fruitland, Idaho 83619

United States

Saint Luke's Cancer Institute - Meridian

Meridian, Idaho 83642

United States

Saint Luke's Cancer Institute - Nampa

Nampa, Idaho 83687

United States

Saint Luke's Cancer Institute - Twin Falls

Twin Falls, Idaho 83301

United States

University of Illinois

Chicago, Illinois 60612

United States

Baptist Health Floyd

New Albany, Indiana 47150

United States

UI Health Care Mission Cancer and Blood - Ankeny Clinic

Ankeny, Iowa 50023

United States

University of Iowa Healthcare Cancer Services Quad Cities

Bettendorf, Iowa 52722

United States

Mercy Cancer Center-West Lakes

Clive, Iowa 50325

United States

UI Health Care Mission Cancer and Blood - West Des Moines Clinic

Clive, Iowa 50325

United States

Greater Regional Medical Center

Creston, Iowa 50801

United States

Iowa Methodist Medical Center

Des Moines, Iowa 50309

United States

UI Health Care Mission Cancer and Blood - Des Moines Clinic

Des Moines, Iowa 50309

United States

Mercy Medical Center - Des Moines

Des Moines, Iowa 50314

United States

UI Health Care Mission Cancer and Blood - Laurel Clinic

Des Moines, Iowa 50314

United States

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa 52242

United States

UI Health Care Mission Cancer and Blood - Waukee Clinic

Waukee, Iowa 50263

United States

Mercy Medical Center-West Lakes

West Des Moines, Iowa 50266

United States

University of Kentucky/Markey Cancer Center

Lexington, Kentucky 40536

United States

Baptist Health Louisville

Louisville, Kentucky 40207

United States

University Medical Center New Orleans

New Orleans, Louisiana 70112

United States

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland 21287

United States

Boston Medical Center

Boston, Massachusetts 02118

United States

Trinity Health Saint Joseph Mercy Hospital Ann Arbor

Ann Arbor, Michigan 48106

United States

Trinity Health IHA Medical Group Hematology Oncology - Brighton

Brighton, Michigan 48114

United States

Trinity Health Medical Center - Brighton

Brighton, Michigan 48114

United States

Trinity Health IHA Medical Group Hematology Oncology - Canton

Canton, Michigan 48188

United States

Trinity Health Medical Center - Canton

Canton, Michigan 48188

United States

Chelsea Hospital

Chelsea, Michigan 48118

United States

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

Chelsea, Michigan 48118

United States

Henry Ford Macomb Hospital-Clinton Township

Clinton Township, Michigan 48038

United States

Corewell Health Dearborn Hospital

Dearborn, Michigan 48124

United States

Henry Ford Hospital

Detroit, Michigan 48202

United States

Corewell Health Farmington Hills Hospital

Farmington Hills, Michigan 48336

United States

Genesys Hurley Cancer Institute

Flint, Michigan 48503

United States

Hurley Medical Center

Flint, Michigan 48503

United States

Allegiance Health

Jackson, Michigan 49201

United States

University of Michigan Health - Sparrow Lansing

Lansing, Michigan 48912

United States

Trinity Health Saint Mary Mercy Livonia Hospital

Livonia, Michigan 48154

United States

Henry Ford Health Providence Novi Hospital

Novi, Michigan 48374

United States

Corewell Health William Beaumont University Hospital

Royal Oak, Michigan 48073

United States

Henry Ford Health Providence Southfield Hospital

Southfield, Michigan 48075

United States

Corewell Health Beaumont Troy Hospital

Troy, Michigan 48085

United States

Henry Ford West Bloomfield Hospital

West Bloomfield, Michigan 48322

United States

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

Ypsilanti, Michigan 48197

United States

Sanford Joe Lueken Cancer Center

Bemidji, Minnesota 56601

United States

Regions Hospital

Saint Paul, Minnesota 55101

United States

Baptist Memorial Hospital and Cancer Center-Golden Triangle

Columbus, Mississippi 39705

United States

Baptist Cancer Center-Grenada

Grenada, Mississippi 38901

United States

Baptist Memorial Hospital and Cancer Center-Union County

New Albany, Mississippi 38652

United States

Baptist Memorial Hospital and Cancer Center-Oxford

Oxford, Mississippi 38655

United States

Baptist Memorial Hospital and Cancer Center-Desoto

Southhaven, Mississippi 38671

United States

MU Health - University Hospital/Ellis Fischel Cancer Center

Columbia, Missouri 65212

United States

Parkland Health Center - Farmington

Farmington, Missouri 63640

United States

Heartland Regional Medical Center

Saint Joseph, Missouri 64506

United States

Sainte Genevieve County Memorial Hospital

Sainte Genevieve, Missouri 63670

United States

Mercy Hospital Springfield

Springfield, Missouri 65804

United States

Mercy Hospital South

St Louis, Missouri 63128

United States

Missouri Baptist Medical Center

St Louis, Missouri 63131

United States

Mercy Hospital Saint Louis

St Louis, Missouri 63141

United States

Missouri Baptist Sullivan Hospital

Sullivan, Missouri 63080

United States

BJC Outpatient Center at Sunset Hills

Sunset Hills, Missouri 63127

United States

Billings Clinic Cancer Center

Billings, Montana 59101

United States

Benefis Sletten Cancer Institute

Great Falls, Montana 59405

United States

Nebraska Medicine-Bellevue

Bellevue, Nebraska 68123

United States

Nebraska Medicine-Village Pointe

Omaha, Nebraska 68118

United States

University of Nebraska Medical Center

Omaha, Nebraska 68198

United States

Renown Regional Medical Center

Reno, Nevada 89502

United States

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire 03756

United States

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey 07920

United States

Englewood Hospital and Medical Center

Englewood, New Jersey 07631

United States

Memorial Sloan Kettering Monmouth

Middletown, New Jersey 07748

United States

Memorial Sloan Kettering Bergen

Montvale, New Jersey 07645

United States

University of New Mexico Cancer Center

Albuquerque, New Mexico 87106

United States

New York-Presbyterian/Brooklyn Methodist Hospital

Brooklyn, New York 11215

United States

Memorial Sloan Kettering Commack

Commack, New York 11725

United States

The New York Hospital Medical Center of Queens

Flushing, New York 11355

United States

Northwell Health Physicians Partners Radiation Medicine at Queens

Forest Hills, New York 11375

United States

Northwell Health Cancer Institute at Huntington

Greenlawn, New York 11740

United States

Memorial Sloan Kettering Westchester

Harrison, New York 10604

United States

Northwell Health/Center for Advanced Medicine

Lake Success, New York 11042

United States

Northern Westchester Hospital

Mount Kisco, New York 10549

United States

Mount Sinai West

New York, New York 10019

United States

Mount Sinai Hospital

New York, New York 10029

United States

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York 10032

United States

Manhattan Eye Ear and Throat Hospital

New York, New York 10065

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

NYP/Weill Cornell Medical Center

New York, New York 10065

United States

Lenox Hill Hospital

New York, New York 10075

United States

Queens Cancer Center

Rego Park, New York 11374

United States

University of Rochester

Rochester, New York 14642

United States

Phelps Memorial Hospital Center

Sleepy Hollow, New York 10591

United States

Memorial Sloan Kettering Nassau

Uniondale, New York 11553

United States

Westchester Medical Center

Valhalla, New York 10595

United States

Wilmot Cancer Institute at Webster

Webster, New York 14580

United States

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina 28203

United States

Atrium Health Cabarrus/LCI-Concord

Concord, North Carolina 28025

United States

East Carolina University

Greenville, North Carolina 27834

United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina 27157

United States

Sanford Bismarck Medical Center

Bismarck, North Dakota 58501

United States

Sanford Broadway Medical Center

Fargo, North Dakota 58122

United States

Sanford Roger Maris Cancer Center

Fargo, North Dakota 58122

United States

Dayton Physicians LLC-Miami Valley South

Centerville, Ohio 45459

United States

Miami Valley Hospital South

Centerville, Ohio 45459

United States

MetroHealth Medical Center

Cleveland, Ohio 44109

United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio 43210

United States

Miami Valley Hospital

Dayton, Ohio 45409

United States

Premier Blood and Cancer Center

Dayton, Ohio 45409

United States

Dayton Physician LLC - Englewood

Dayton, Ohio 45415

United States

Miami Valley Hospital North

Dayton, Ohio 45415

United States

Atrium Medical Center-Middletown Regional Hospital

Franklin, Ohio 45005-1066

United States

Dayton Physicians LLC-Atrium

Franklin, Ohio 45005

United States

Miami Valley Cancer Care and Infusion

Greenville, Ohio 45331

United States

Upper Valley Medical Center

Troy, Ohio 45373

United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma 73104

United States

Oregon Health and Science University

Portland, Oregon 97239

United States

Christiana Care Health System-Concord Health Center

Chadds Ford, Pennsylvania 19317

United States

Geisinger Medical Center

Danville, Pennsylvania 17822

United States

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania 17033-0850

United States

Lancaster General Ann B Barshinger Cancer Institute

Lancaster, Pennsylvania 17601

United States

Geisinger Medical Oncology-Lewisburg

Lewisburg, Pennsylvania 17837

United States

Allegheny General Hospital

Pittsburgh, Pennsylvania 15212

United States

West Penn Hospital

Pittsburgh, Pennsylvania 15224

United States

Geisinger Wyoming Valley/Henry Cancer Center

Wilkes-Barre, Pennsylvania 18711

United States

Sanford Cancer Center Oncology Clinic

Sioux Falls, South Dakota 57104

United States

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota 57117-5134

United States

Baptist Memorial Hospital and Cancer Center-Memphis

Memphis, Tennessee 38120

United States

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee 37232

United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas 78229

United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah 84112

United States

Bon Secours Memorial Regional Medical Center

Mechanicsville, Virginia 23116

United States

Bon Secours Saint Francis Medical Center

Midlothian, Virginia 23114

United States

Bon Secours Saint Mary's Hospital

Richmond, Virginia 23226

United States

Bon Secours Cancer Institute at Reynolds Crossing

Richmond, Virginia 23230

United States

Valley Medical Center

Renton, Washington 98055

United States

Edwards Comprehensive Cancer Center

Huntington, West Virginia 25701

United States

Aspirus Cancer Care-Antigo-Volm Cancer Center

Antigo, Wisconsin 54409

United States

Ascension Northeast Wisconsin-Saint Elizabeth Cancer Center-Appleton

Appleton, Wisconsin 54915

United States

Ascension Southeast Wisconsin Hospital-Elmbrook Campus-Brookfield

Brookfield, Wisconsin 53045

United States

Ascension Calumet Hospital-Chilton

Chilton, Wisconsin 53014

United States

Ascension Southeast Wisconsin Hospital - Franklin

Franklin, Wisconsin 53132

United States

Ascension Columbia Saint Mary's Hospital-Ozaukee Campus-Mequon

Mequon, Wisconsin 53097

United States

Ascension Southeast Wisconsin Hospital-Saint Joseph-Milwaukee

Milwaukee, Wisconsin 53210

United States

Ascension Columbia Saint Mary's Hospital-Milwaukee Campus

Milwaukee, Wisconsin 53211

United States

Medical College of Wisconsin

Milwaukee, Wisconsin 53226

United States

Ascension Northeast Wisconsin-Mercy Hospital-Oshkosh

Oshkosh, Wisconsin 54904

United States

Ascension All Saints Hospital-Spring Street-Racine

Racine, Wisconsin 53405

United States

Aspirus Cancer Care-Rhinelander-James Beck Cancer Center

Rhinelander, Wisconsin 54501

United States

Aspirus Cancer Care - Stevens Point

Stevens Point, Wisconsin 54481

United States

Aspirus Cancer Care-Wausau

Wausau, Wisconsin 54401

United States

Ascension Southeast Wisconsin Hospital-Mayfair Road-Wauwatosa

Wauwatosa, Wisconsin 53226

United States

Aspirus Cancer Care - Wisconsin Rapids

Wisconsin Rapids, Wisconsin 54494

United States

Arthur J E Child Comprehensive Cancer Centre

Calgary, Alberta T2N 5G2

Canada