ctDNA-Directed Chemotherapy after Hepatectomy for the Treatment of Colorectal Liver Metastases

PRIMARY OBJECTIVE:

I. To assess 1-year recurrence-free survival rate following liver resection of colorectal liver metastases (CLM) with curative intent among circulating tumor-derived deoxyribonucleic acid (ctDNA)-negative patients who receive risk-stratified postoperative chemotherapy.

SECONDARY OBJECTIVES:

I. To assess recurrence-free survival following liver resection of CLM with curative intent among ctDNA-positive patients.

II. To assess overall survival following liver resection among ctDNA-negative and ctDNA-positive patients.

III. To evaluate the proportion of ctDNA-negative at 1-year post-resection.

IV. To compare survival of ctDNA-negative patients undergoing ctDNA-guided postoperative chemotherapy to historical controls.

V. To evaluate proportion of patients in each arm who change chemotherapy in response to ctDNA measurement.

VI. To delineate the pattern of disease recurrence.

VII. To assess ctDNA sensitivity and specificity for predicting disease recurrence.

VIII. To evaluate MD Anderson Symptom Inventory - Gastrointestinal (MDASI-GI) during the course of postoperative therapy.

IX. To evaluate and correlate patient molecular subtypes and characterization of tumor biologic factors that are associated with ctDNA detection.

X. To evaluate surgery-related adverse events occurring up to 90 days after surgery, and chemo-related adverse events occurring up to 30 days after the last dose of chemotherapy.

OUTLINE:

Patients undergo collection of blood and tumor specimens during standard hepatectomy. After genetic analysis of blood and tumor specimens, patients negative for ctDNA are assigned to Arm I, and patients positive for ctDNA are assigned to Arm II.

ARM I: Patients receive capecitabine orally (PO) or fluorouracil intravenously (IV) for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients may instead receive no chemotherapy/surveillance per treating physician.

ARM II: Patients receive FOLFOX regimen consisting of fluorouracil, leucovorin calcium, and oxaliplatin, or FOLFIRI regimen consisting of fluorouracil, leucovorin calcium, and irinotecan for up to 12 months in the absence of disease progression or unacceptable toxicity.

All patients continue to undergo collection of blood specimens for ctDNA analysis during post-hepatectomy treatment. Individual treating physicians may decide to escalate, de-escalate, or stop chemotherapy for either treatment arm depending on changes in ctDNA.