ctDNA-Directed Post-Hepatectomy Chemotherapy for Patients With Resectable Colorectal Liver Metastases
Primary Purpose
Liver Metastases
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Leucovorin
5-FLUOROURACIL
Oxaliplatin
Irinotecan
Capecitabine
Bevacizumab
Sponsored by
About this trial
This is an interventional treatment trial for Liver Metastases
Eligibility Criteria
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
Sites / Locations
- M D Anderson Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
ctDNA (Low Risk)
ctDNA (High Risk)
Arm Description
Will receive less intense chemotherapy, such as capecitabine or 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)
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Full Information
NCT ID
NCT05062317
First Posted
September 21, 2021
Last Updated
October 6, 2023
Sponsor
M.D. Anderson Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT05062317
Brief Title
ctDNA-Directed Post-Hepatectomy Chemotherapy for Patients With Resectable Colorectal Liver Metastases
Official Title
Risk-Stratified Adjuvant Therapy: ctDNA-Directed Post-Hepatectomy Chemotherapy for Patients With Resectable Colorectal Liver Metastases
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 26, 2022 (Actual)
Primary Completion Date
February 28, 2026 (Anticipated)
Study Completion Date
February 28, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Metastases
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ctDNA (Low Risk)
Arm Type
Experimental
Arm Description
Will receive less intense chemotherapy, such as capecitabine or 5-fluorouracil.
Arm Title
ctDNA (High Risk)
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Other Intervention Name(s)
Citrovorum, Wellcovorin®
Intervention Description
Given by PO
Intervention Type
Drug
Intervention Name(s)
5-FLUOROURACIL
Intervention Description
Given by IV
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
Eloxatin
Intervention Description
Given by PO
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Intervention Description
Given by IV
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
Given by IV
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin™, Anti-VEGF monoclonal antibody, rhuMAb-VEGF
Intervention Description
Given by IV
Primary Outcome Measure Information:
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Timothy Newhook
Phone
(713) 794-1001
Email
tnewhook@mdanderson.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Timothy Newhook
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Timothy Newhook
Phone
713-794-1001
Email
tnewhook@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Timothy Newhook
12. IPD Sharing Statement
Links:
URL
http://www.mdanderson.org
Description
M D Anderson Cancer Center website
Learn more about this trial
ctDNA-Directed Post-Hepatectomy Chemotherapy for Patients With Resectable Colorectal Liver Metastases
We'll reach out to this number within 24 hrs