This phase III trial compares the addition of total ablative therapy to the usual systemic therapy versus the usual systemic therapy alone in treating patients with advanced 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 (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. The ablative local therapy will consist of any combination of very focused, intensive radiotherapy called stereotactic ablative radiotherapy (SABR), surgical resection, 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. The addition of ablative local therapy to the usual approach of systemic therapy could be more effective than usual chemotherapy alone by increasing the life of patients with limited metastatic colorectal cancer.
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 any combination of SABR surgical resection or microwave ablation on study. 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. Additionally, patients may undergo endoscopic exam and optional blood sample collection throughout the trial. ARM 2: Patients receive SOC chemotherapy on study. Patients also undergo CT or MRI or PET/CT scans throughout the trial. . Additionally, patients may undergo endoscopic exam and optional blood sample collection throughout the trial. After completion of study treatment, patients are followed for 5 years from the date of registration.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
146
Undergo SABR
undergo surgical resection
undergo microwave ablation
Receive SOC chemotherapy
Undergo CT scan
Undergo MRI
Undergo PET scan
Kingman Regional Medical Center
Kingman, Arizona, United States
RECRUITINGMayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
RECRUITINGTower Cancer Research Foundation
Beverly Hills, California, United States
RECRUITINGUCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, United States
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
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.
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)
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).
Time frame: Up to 5 years
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.
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
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Cedars-Sinai Medical Center
Los Angeles, California, United States
RECRUITINGUC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States
RECRUITINGUniversity of California Davis Comprehensive Cancer Center
Sacramento, California, United States
ACTIVE_NOT_RECRUITINGBeebe Medical Center
Lewes, Delaware, United States
RECRUITINGBeebe South Coastal Health Campus
Millville, Delaware, United States
RECRUITINGHelen F Graham Cancer Center
Newark, Delaware, United States
RECRUITING...and 177 more locations