ctDNA-Directed Post-Hepatectomy Chemotherapy for Patients With Resectable Colorectal Liver Metastases

Study Overview
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Brief Summary
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To determine if the detection of ctDNA after surgical resection of CLM can stratify patients into high and low-risk cohorts for early disease recurrence in order to inform post-operative adjuvant therapy.

Detailed Description
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Primary Objective: • To assess 1-year recurrence-free survival rate following liver resection of CLM with curative intent among ctDNA-negative patients who receive risk-stratified postoperative chemotherapy Secondary Objectives: To assess recurrence-free survival following liver resection of CLM with curative intent among ctDNA-positive patients To assess overall survival following liver resection among ctDNA-negative and ctDNA-positive patients To evaluate the proportion of ctDNA-negative at 1-year post-resection To compare survival of ctDNA-negative patients undergoing ctDNA-guided postoperative chemotherapy to historical controls To evaluate proportion of patients in each arm who change chemotherapy in response to ctDNA measurement To delineate the pattern of disease recurrence To assess ctDNA sensitivity and specificity for predicting disease recurrence To evaluate MDASI-GI during the course of postoperative therapy To evaluate and correlate patient molecular subtypes and characterization of tumor biologic factors that are associated with ctDNA detection 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 Outcome Measures: Primary: • Recurrence-free survival at 1-year post-hepatectomy among ctDNA-negative patients Secondary: Recurrence-free survival at 1-year post-hepatectomy among ctDNA-positive patients Overall survival (OS) among ctDNA-negative and ctDNA-positive patients ctDNA-negativity at 1-year post-resection Proportion of patients in each group with chemotherapy regimen change in response to ctDNA dynamics Pattern of disease recurrence (i.e., liver, systemic, salvageable vs. unsalvageable) ctDNA sensitivity/specificity for recurrent disease overall by timepoint MDASI-GI at clinic visits during course of postoperative therapy Tumor radiologic, histologic, and molecular profiling and correlative characterization based upon ctDNA detection Adverse events

Official Title
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Risk-Stratified Adjuvant Therapy: ctDNA-Directed Post-Hepatectomy Chemotherapy for Patients With Resectable Colorectal Liver Metastases

Conditions
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Liver Metastases

Intervention / Treatment
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* Drug: Leucovorin
* Drug: 5-FLUOROURACIL
* Drug: Oxaliplatin
* Drug: Irinotecan
* Drug: Capecitabine
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥18 years of age with CLM undergoing elective hepatectomy with curative intent (primary colorectal primary cancer previously removed OR being removed at time of hepatectomy) after preoperative chemotherapy (i.e., FOLFOX/FOLFIRI +/- bevacizumab or panitumumab/cetuximab) from 07/01/2021 - 12/31/2023 Must receive ≥ 4 cycles of preoperative chemotherapy Exclusion Criteria: Patients with primary colorectal tumor that will remain in situ Inability to undergo postoperative chemotherapy, or postoperative chemotherapy not planned a priori Unwilling/unable to undergo blood draws for ctDNA, patient or provider-determined Other active malignancies requiring treatment Women who are pregnant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ctDNA (Low Risk)<br>Will receive less intense chemotherapy, such as capecitabine or 5-fluorouracil. | Drug: Leucovorin<br>* Given by PO<br>* Other names: Wellcovorin®;Drug: Capecitabine<br>* Given by IV<br>* Other names: Xeloda;|
| Experimental: ctDNA (High Risk)<br>Will receive more intense chemotherapy. This may include resuming the chemotherapy you received before surgery (for example, FOLFOX [5-fluorouracil, leucovorin and oxaliplatin] or FOLFIRI [5-fluorouracil, leucovorin and irinotecan] with or without bevacizumab) | Drug: Leucovorin<br>* Given by PO<br>* Other names: Wellcovorin®;Drug: 5-FLUOROURACIL<br>* Given by IV<br>Drug: Oxaliplatin<br>* Given by PO<br>* Other names: Eloxatin;Drug: Irinotecan<br>* Given by IV<br>Drug: Capecitabine<br>* Given by IV<br>* Other names: Xeloda;Drug: Bevacizumab<br>* Given by IV<br>* Other names: rhuMAb-VEGF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To establish the 1-year recurrence-free survival rate following liver resection of CLM with curative intent among ctDNA-negative patients who receive risk-stratified postoperative chemotherapy |  | through study completion, an average of 1 year |