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

Stage IV Colorectal Cancer AJCC v8 Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05673148
• Other study ID #: A022101
• Secondary ID: NCI-2022-09253
• Status: Recruiting
• Phase: Phase 3
• Start date: January 10, 2023
• Est. completion date: August 12, 2032

Study information

• Verified date: April 2024
• Source: Alliance for Clinical Trials in Oncology
• Contact: Eric D. Miller, MD, PhD
• Phone: 614-685-4922
• Email: eric.miller[@]osumc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 364
• Est. completion date: August 12, 2032
• Est. primary completion date: June 3, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Adenocarcinoma
• Stage IV Colorectal Cancer AJCC v8

Intervention

Procedure:
• Stereotactic Ablative Radiotherapy
Undergo SABR
• Resection
undergo surgical resection
• Microwave Ablation
undergo microwave ablation

Drug:
• Chemotherapy
Receive SOC chemotherapy

Procedure:
• Computed Tomography
Undergo CT scan
• Magnetic Resonance Imaging
Undergo MRI
• Positron Emission Tomography
Undergo PET scan

Locations

Country	Name	City	State
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Mission Cancer and Blood - Ankeny	Ankeny	Iowa
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Emory Proton Therapy Center	Atlanta	Georgia
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Grady Health System	Atlanta	Georgia
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	Nebraska Medicine-Bellevue	Bellevue	Nebraska
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Tower Cancer Research Foundation	Beverly Hills	California
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan
United States	New York-Presbyterian/Brooklyn Methodist Hospital	Brooklyn	New York
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Canton	Canton	Michigan
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Baptist Memorial Hospital and Cancer Center-Golden Triangle	Columbus	Mississippi
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	Greater Regional Medical Center	Creston	Iowa
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton Blood and Cancer Center	Dayton	Ohio
United States	Dayton Physician LLC-Miami Valley Hospital North	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Beaumont Hospital - Dearborn	Dearborn	Michigan
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	The New York Hospital Medical Center of Queens	Flushing	New York
United States	Northwell Health Physicians Partners Radiation Medicine at Queens	Forest Hills	New York
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Northwell Health Cancer Institute at Huntington	Greenlawn	New York
United States	Miami Valley Cancer Care and Infusion	Greenville	Ohio
United States	Baptist Cancer Center-Grenada	Grenada	Mississippi
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Kingman Regional Medical Center	Kingman	Arizona
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	University of Michigan Health - Sparrow Lansing	Lansing	Michigan
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Baptist Memorial Hospital and Cancer Center-Memphis	Memphis	Tennessee
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Northern Westchester Hospital	Mount Kisco	New York
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Baptist Memorial Hospital and Cancer Center-Union County	New Albany	Mississippi
United States	Lenox Hill Hospital	New York	New York
United States	Manhattan Eye Ear and Throat Hospital	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	Ascension Providence Hospitals - Novi	Novi	Michigan
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Medicine-Village Pointe	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Baptist Memorial Hospital and Cancer Center-Oxford	Oxford	Mississippi
United States	Mayo Clinic Hospital in Arizona	Phoenix	Arizona
United States	Queens Cancer Center	Rego Park	New York
United States	Renown Regional Medical Center	Reno	Nevada
United States	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin
United States	University of Rochester	Rochester	New York
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Ascension Providence Hospitals - Southfield	Southfield	Michigan
United States	Baptist Memorial Hospital and Cancer Center-Desoto	Southhaven	Mississippi
United States	Upper Valley Medical Center	Troy	Ohio
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Memorial Sloan Kettering Nassau	Uniondale	New York
United States	Westchester Medical Center	Valhalla	New York
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	Wilmot Cancer Institute at Webster	Webster	New York
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus	Ypsilanti	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	From the date of randomization to the date of death due to all causes, assessed up to 5 years
Secondary	Event Free Survival (EFS)	The hazard ratio (HR) for EFS 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 EFS for each treatment arm, and Kaplan-Meier curves will be produced. EFS will also be compared between treatment arms using the log rank test.	From randomization to the date of first documented progression, recurrence, or death due to all causes, whichever occurs first, assessed up to 5 years
Secondary	• Incidence of Adverse Events (AEs), assessed using National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) version 5.0 (v5.0)	Defined as the proportion of patients experienced at least one Grade 3, Grade 4, or Grade 5 of each type of AE. The maximum grade for each type of adverse events that are possibly, probably, or definitely related to study treatments will be recorded for each patient. The frequency tables will be reviewed to determine the patterns. The overall adverse event rates for grade 3 or higher adverse events will be compared between two treatment groups using Chi-square test (or Fisher's exact test if the data in the contingency table is sparse).	Up to 5 years
Secondary	Time to local recurrence (TLR)	TLR will be measured only for patients who receive treatment with TAT and is defined as the time from the end of TAT until the date of first documented recurrence at any disease site treated with TAT. The Kaplan-Meier methodology will be used to estimate the median TLR for patients treated with TAT , and a Kaplan-Meier curve will be produced.	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