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

April 18, 2024 updated by: M.D. Anderson Cancer Center

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • M D Anderson Cancer Center
        • Contact:
        • Principal Investigator:
          • Timothy Newhook

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ctDNA (Low Risk)
Will receive less intense chemotherapy, such as capecitabine or 5-fluorouracil.
Drug: Leucovorin
Given by PO
Other Names:
  • Citrovorum
  • Wellcovorin®
Drug: Capecitabine
Given by IV
Other Names:
  • Xeloda
Experimental: ctDNA (High Risk)
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
Given by PO
Other Names:
  • Citrovorum
  • Wellcovorin®
Drug: Capecitabine
Given by IV
Other Names:
  • Xeloda
Drug: 5-FLUOROURACIL
Given by IV
Drug: Oxaliplatin
Given by PO
Other Names:
  • Eloxatin
Drug: Irinotecan
Given by IV
Drug: Bevacizumab
Given by IV
Other Names:
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
  • Avastin™

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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
Time Frame: through study completion, an average of 1 year
through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Investigators

  • Principal Investigator: Timothy Newhook, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 26, 2022

Primary Completion (Estimated)

February 28, 2026

Study Completion (Estimated)

February 28, 2026

Study Registration Dates

First Submitted

September 21, 2021

First Submitted That Met QC Criteria

September 29, 2021

First Posted (Actual)

September 30, 2021

Study Record Updates

Last Update Posted (Actual)

April 19, 2024

Last Update Submitted That Met QC Criteria

April 18, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021-0584

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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