Clinical trial NCT05673148: Testing the Addition of Total Ablative Therapy to Usual Systemic Therapy Treatment for Limited Metastatic Colorectal Cancer, the ERASur Study
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Metastatic Colorectal Adenocarcinoma
Stage IV Colorectal Cancer AJCC V8
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2023-01-06
Enrollment: 364
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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: 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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From the date of randomization to the date of death due to all causes, assessed up to 5 years
Secondary outcomes:
measure: Event Free Survival (EFS)
timeFrame: From randomization to the date of first documented progression, recurrence, or death due to all causes, whichever occurs first, assessed up to 5 years
measure: • Incidence of Adverse Events (AEs), assessed using National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) version 5.0 (v5.0)
timeFrame: Up to 5 years
measure: Time to local recurrence (TLR)
timeFrame: 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
Other outcomes:
Locations:
city: Kingman
country: United States
facility: Kingman Regional Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Hospital in Arizona
state: Arizona
city: Beverly Hills
country: United States
facility: Tower Cancer Research Foundation
state: California
city: Irvine
country: United States
facility: UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Orange
country: United States
facility: UC Irvine Health/Chao Family Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: Lewes
country: United States
facility: Beebe Medical Center
state: Delaware
city: Millville
country: United States
facility: Beebe South Coastal Health Campus
state: Delaware
city: Newark
country: United States
facility: Helen F Graham Cancer Center
state: Delaware
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants PA
state: Delaware
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Rehoboth Beach
country: United States
facility: Beebe Health Campus
state: Delaware
city: Washington
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida Health Science Center - Gainesville
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Atlanta
country: United States
facility: Grady Health System
state: Georgia
city: Atlanta
country: United States
facility: Emory Proton Therapy Center
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Atlanta
country: United States
facility: Emory Saint Joseph's Hospital
state: Georgia
city: Boise
country: United States
facility: Saint Luke's Cancer Institute - Boise
state: Idaho
city: Fruitland
country: United States
facility: Saint Luke's Cancer Institute - Fruitland
state: Idaho
city: Meridian
country: United States
facility: Saint Luke's Cancer Institute - Meridian
state: Idaho
city: Nampa
country: United States
facility: Saint Luke's Cancer Institute - Nampa
state: Idaho
city: Twin Falls
country: United States
facility: Saint Luke's Cancer Institute - Twin Falls
state: Idaho
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Ankeny
country: United States
facility: Mission Cancer and Blood - Ankeny
state: Iowa
city: Clive
country: United States
facility: Mercy Cancer Center-West Lakes
state: Iowa
city: Clive
country: United States
facility: Mission Cancer and Blood - West Des Moines
state: Iowa
city: Creston
country: United States
facility: Greater Regional Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Mission Cancer and Blood - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Mission Cancer and Blood - Laurel
state: Iowa
city: West Des Moines
country: United States
facility: Mercy Medical Center-West Lakes
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky/Markey Cancer Center
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: Ann Arbor
country: United States
facility: Trinity Health Saint Joseph Mercy Hospital Ann Arbor
state: Michigan
city: Brighton
country: United States
facility: Trinity Health IHA Medical Group Hematology Oncology - Brighton
state: Michigan
city: Brighton
country: United States
facility: Trinity Health Medical Center - Brighton
state: Michigan
city: Canton
country: United States
facility: Trinity Health IHA Medical Group Hematology Oncology - Canton
state: Michigan
city: Canton
country: United States
facility: Trinity Health Medical Center - Canton
state: Michigan
city: Chelsea
country: United States
facility: Chelsea Hospital
state: Michigan
city: Chelsea
country: United States
facility: Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
state: Michigan
city: Dearborn
country: United States
facility: Corewell Health Dearborn Hospital
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Farmington Hills
country: United States
facility: Corewell Health Farmington Hills Hospital
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Lansing
country: United States
facility: University of Michigan Health - Sparrow Lansing
state: Michigan
city: Livonia
country: United States
facility: Trinity Health Saint Mary Mercy Livonia Hospital
state: Michigan
city: Novi
country: United States
facility: Henry Ford Health Providence Novi Hospital
state: Michigan
city: Royal Oak
country: United States
facility: Corewell Health William Beaumont University Hospital
state: Michigan
city: Southfield
country: United States
facility: Henry Ford Health Providence Southfield Hospital
state: Michigan
city: Troy
country: United States
facility: Corewell Health Beaumont Troy Hospital
state: Michigan
city: Ypsilanti
country: United States
facility: Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
state: Michigan
city: Bemidji
country: United States
facility: Sanford Joe Lueken Cancer Center
state: Minnesota
city: Columbus
country: United States
facility: Baptist Memorial Hospital and Cancer Center-Golden Triangle
state: Mississippi
city: Grenada
country: United States
facility: Baptist Cancer Center-Grenada
state: Mississippi
city: New Albany
country: United States
facility: Baptist Memorial Hospital and Cancer Center-Union County
state: Mississippi
city: Oxford
country: United States
facility: Baptist Memorial Hospital and Cancer Center-Oxford
state: Mississippi
city: Southhaven
country: United States
facility: Baptist Memorial Hospital and Cancer Center-Desoto
state: Mississippi
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Great Falls
country: United States
facility: Benefis Sletten Cancer Institute
state: Montana
city: Bellevue
country: United States
facility: Nebraska Medicine-Bellevue
state: Nebraska
city: Omaha
country: United States
facility: Nebraska Medicine-Village Pointe
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Reno
country: United States
facility: Renown Regional Medical Center
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
state: New Hampshire
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Brooklyn
country: United States
facility: New York-Presbyterian/Brooklyn Methodist Hospital
state: New York
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack
state: New York
city: Flushing
country: United States
facility: The New York Hospital Medical Center of Queens
state: New York
city: Forest Hills
country: United States
facility: Northwell Health Physicians Partners Radiation Medicine at Queens
state: New York
city: Greenlawn
country: United States
facility: Northwell Health Cancer Institute at Huntington
state: New York
city: Lake Success
country: United States
facility: Northwell Health/Center for Advanced Medicine
state: New York
city: Mount Kisco
country: United States
facility: Northern Westchester Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai West
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Manhattan Eye Ear and Throat Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: NYP/Weill Cornell Medical Center
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital
state: New York
city: Rego Park
country: United States
facility: Queens Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
city: Valhalla
country: United States
facility: Westchester Medical Center
state: New York
city: Webster
country: United States
facility: Wilmot Cancer Institute at Webster
state: New York
city: West Harrison
country: United States
facility: Memorial Sloan Kettering Westchester
state: New York
city: Bismarck
country: United States
facility: Sanford Bismarck Medical Center
state: North Dakota
city: Fargo
country: United States
facility: Sanford Broadway Medical Center
state: North Dakota
city: Fargo
country: United States
facility: Sanford Roger Maris Cancer Center
state: North Dakota
city: Centerville
country: United States
facility: Dayton Physicians LLC-Miami Valley South
state: Ohio
city: Centerville
country: United States
facility: Miami Valley Hospital South
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Premier Blood and Cancer Center
state: Ohio
city: Dayton
country: United States
facility: Dayton Physician LLC - Englewood
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital North
state: Ohio
city: Franklin
country: United States
facility: Atrium Medical Center-Middletown Regional Hospital
state: Ohio
city: Franklin
country: United States
facility: Dayton Physicians LLC-Atrium
state: Ohio
city: Greenville
country: United States
facility: Miami Valley Cancer Care and Infusion
state: Ohio
city: Troy
country: United States
facility: Upper Valley Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Chadds Ford
country: United States
facility: Christiana Care Health System-Concord Health Center
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Lewisburg
country: United States
facility: Geisinger Medical Oncology-Lewisburg
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: West Penn Hospital
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Geisinger Wyoming Valley/Henry Cancer Center
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Cancer Center Oncology Clinic
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford USD Medical Center - Sioux Falls
state: South Dakota
city: Memphis
country: United States
facility: Baptist Memorial Hospital and Cancer Center-Memphis
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University/Ingram Cancer Center
state: Tennessee
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Renton
country: United States
facility: Valley Medical Center
state: Washington
city: Antigo
country: United States
facility: Langlade Hospital and Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Rhinelander
country: United States
facility: Aspirus Cancer Care - James Beck Cancer Center
state: Wisconsin
city: Stevens Point
country: United States
facility: Aspirus Cancer Care - Stevens Point
state: Wisconsin
city: Wisconsin Rapids
country: United States
facility: Aspirus Cancer Care - Wisconsin Rapids
state: Wisconsin
Study officials:
References: