Clinical trial NCT05062317: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Liver Metastases
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
First posted: 2021-09-30
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: 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
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Timothy Newhook
role: PRINCIPAL_INVESTIGATOR
References: