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

Inclusion Criteria:

• PRE-REGISTRATION (STEP 0): Histologically-confirmed metastatic colorectaladenocarcinoma

• 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 iffollow-up brain imaging after central nervous system (CNS)-directed therapy shows noevidence of progression. No known peritoneal and/or omental metastases. Ifradiologic studies suggest the presence of peritoneal disease, a diagnosticlaparoscopy is recommended to verify the absence of peritoneal implants

• PRE-REGISTRATION (STEP 0): Primary tumor is already resected OR primary tumor issurgically amenable to resection, as determined by consultation and documentationwith surgeon or documentation of discussion in the institutional multi-disciplinarytumor board where a surgeon confirms resectability. Patients with unresectableprimary tumors are not eligible

• PRE-REGISTRATION (STEP 0): Four (4) or fewer apparent sites of metastatic diseasebased on review by local medical team of baseline radiographic imaging obtainedprior to initiation of systemic therapy.

• Sites of metastatic disease must be radiographically evident, but pathologicconfirmation is not required.

• Liver-only metastatic disease is NOT permitted. For patients with livermetastases, there must be at least one other site of metastasis in addition tothe 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 seenby a radiation oncologist in consultation to verify eligibility.

• Single sites include:

• Each hemiliver (right and left), each lobe of the lungs, each adrenalgland, lymph nodes amenable to a single resection or treatment in a singleSABR field, bone metastases amenable to treatment in a single SABR field

• PRE-REGISTRATION (STEP 0): Patients must have measurable disease per ResponseEvaluation Criteria in Solid Tumors (RECIST) version (v)1.1

• PRE-REGISTRATION (STEP 0): A maximum of 16 weeks (4 months) of systemic therapy maybe administered prior to pre-registration

• REGISTRATION (STEP 1): Patients must have no overt evidence of disease progressionduring systemic therapy prior to registration

• REGISTRATION (STEP 1): Not eligible for hepatic artery infusion pump (HAIP) therapyor 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-linesystemic therapy for metastatic disease for a minimum of 16 weeks (4 months) and amaximum 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 anagent or treatment that has known genotoxic, mutagenic, and teratogenic effects.

• Therefore, for women of childbearing potential only, a negative pregnancy testdone =< 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-oxaloacetictransaminase [SGOT]) / alanine aminotransferase (ALT)(serum glutamate pyruvatetransaminase [SGPT]) =< 3.0 x ULN

• In the event of metastatic liver disease, =< 5 x ULN

• REGISTRATION (STEP 1): Human immunodeficiency virus (HIV)-infected patients oneffective anti-retroviral therapy with undetectable viral load within 6 months areeligible for this trial. Note: HIV testing is not required for eligibility

• REGISTRATION (STEP 1): No other planned concurrent investigational agents while onstudy

Exclusion Criteria:

• N/A