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

Phase 2

Recruiting

• Conditions: Liver Metastases
• Interventions: Drug: Leucovorin; Drug: Capecitabine; Drug: 5-FLUOROURACIL; Drug: Oxaliplatin; Drug: Irinotecan; Drug: Bevacizumab

• Registration Number: NCT05062317
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

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

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

Study Timeline

• Study First Submitted: 2021-09-21
• Study First Submitted QC: 2021-09-29
• Study First Posted: 2021-09-30
• Study Start: 2022-04-26
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-12
• Last Update Posted: 2025-05-15
• Primary Completion: 2026-02-28
• Study Completion: 2026-02-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ctDNA (Low Risk)	Capecitabine	Will receive less intense chemotherapy, such as capecitabine or 5-fluorouracil.
ctDNA (Low Risk)	Leucovorin	Will receive less intense chemotherapy, such as capecitabine or 5-fluorouracil.
ctDNA (High Risk)	5-FLUOROURACIL	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)
ctDNA (High Risk)	Leucovorin	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)
ctDNA (High Risk)	Irinotecan	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)
ctDNA (High Risk)	Oxaliplatin	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)
ctDNA (High Risk)	Capecitabine	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)
ctDNA (High Risk)	Bevacizumab	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)

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States