Regorafenib and XmAb20717 in Treatment of High-risk Patients With Colorectal Cancer With Radiographic Occult Molecular Residual Disease After End of Established Definitive Therapy (RX-CROME)

NCT05900648•M.D. Anderson Cancer Center

Summary

To measure the level of circulating tumor DNA (ctDNA) in the blood of colorectal cancer patients after 6 months of receiving therapy with regorafenib and XmAb20717 (also known as vudalimab). ctDNA is genetic material from tumor cells that can be found and measured in the blood

Detailed Description

Primary Objective: 1\. To determine the 6-month circulating tumor (ctDNA) clearance rate following 6 months of therapy with regorafenib and XmAb20717 (RX regimen) in patients with colorectal cancer (CRC) who present with radiographic occult molecular residual disease (MRD) after completing definitive standard-of-care (SOC) therapy. Secondary Objectives: 1. To determine the 3-month ctDNA clearance rate following RX treatment. 2. To determine disease-free survival (DFS) following 6 months of RX treatment. 3. To determine overall survival (OS) following 6 months of RX treatment. 4. To determine the safety and tolerability of RX. Exploratory Objectives: 1. To determine changes in profiles of circulating lymphocytes and ctDNA (including time to ctDNA negative status, duration of ctDNA negative status, overall ctDNA negative rate, lead time from ctDNA detection to radiographic detection) during and following treatment with RX. 2. To determine baseline characteristics in archival tumor and/or plasma that may predict clinical benefit or lack thereof (including but not limited to immune profiles of tumor-infiltrating lymphocytes, expression of immune markers in tumor cells and microenvironment, and tumor molecular profile).

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Histological confirmation of CRC
•2. Post-R0 resection of stages II, III, or IV CRC and all planned adjuvant therapies have been completed
•3. No evidence of radiographic disease within 28 days (before or after) of a positive ctDNA assay
•4. Evident MRD as defined by positive ctDNA assay. Patients may be identified for enrollment with any Clinical Laboratory Improvement Amendments (CLIA)-certified ctDNA assay for MRD. MRD status will be confirmed with the Signatera assay prior to initiation of therapy (unless the prior testing was also done with Signatera in which case this test would not require confirmation)
•5. Adequate organ and marrow function as defined below:
•1. Absolute neutrophil count: ≥1,000/mcL
•2. Platelets: ≥100,000/mcL
•3. Total bilirubin ≤1.5 x the upper limit of normal (ULN). Total bilirubin (≤3 x ULN) is allowed if Gilbert's syndrome is documented.
•4. AST(SGOT)/ALT(SGPT): ≤3 × institutional ULN (≤5 x ULN for patients with liver involvement of their cancer).
•5. Creatinine clearance ≥40 mL/min. Creatinine clearance (Clcr) can either be measured in a 24-hour urine collection or estimated by the Cockcroft-Gault equation as follows: Clcr (mL/min) = \[(140 - age) x (weight in kg) ÷ \[72 x (serum creatinine in mg/dL)\] \[0.85 if female\]
+8 more criteria

Exclusion Criteria

•1. Concurrent treatment with drug with which the interactions are considered clinically significant by investigator (as outlined in section 5.2). Major surgical procedure or significant traumatic injury within 21 days before start of study medication. Note: If participants received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
•2. Systemic therapy with immunosuppressive agents within 7 days or use of any investigational drug within 28 days before the start of trial treatment.
•3. Prior exposure to any immune checkpoint blockade agent or any other immunomodulatory agent used for antineoplastic therapy for mCRC.
•4. Previous malignant disease (other than the target malignancy to be investigated in this trial) within 3 years prior to study treatment initiation.
•5. Receipt of any organ transplantation, including allogeneic stem cell transplantation (exception: transplants that do not require immunosuppression, such as hair transplant).
•6. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
•7. Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI-CTCAE v4.03), any history of anaphylaxis, or recent (within 5 months) history of uncontrolled asthma.
•8. Clinically significant cardiovascular/ cerebrovascular disease as follows: cerebral vascular accident / stroke (\<6 months prior to enrollment), myocardial infarction (\<6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class \>II), or serious cardiac arrhythmia.
•9. Clinically relevant diseases (for example, inflammatory bowel disease) and / or uncontrolled medical conditions, which, in the opinion of the Investigator, might impair the subject's tolerance or ability to participate in the trial.
•10. Failure to recover from any other toxicity (other than immune-related toxicity) related to previous anticancer treatment to ≤ Grade 2.
+6 more criteria

Key Dates

Start Date

May 17, 2023

Primary Completion Date

February 9, 2024

Completion Date

February 9, 2024

Last Updated

April 29, 2024

Conditions

Colorectal CancerColon CancerRectum Cancer

Interventions

Regorafenib

DRUG

XmAb20717

DRUG

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: April 29, 2024Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Regorafenib and XmAb20717 in Treatment of High-risk Patients With Colorectal Cancer With Radiographic Occult Molecular Residual Disease After End of Established Definitive Therapy (RX-CROME)

Inclusion Criteria

Exclusion Criteria

Clinical Trial of an Anti-cancer Drug, CA-4948 (Emavusertib), in Combination With Chemotherapy Treatment (FOLFOX Plus Bevacizumab) in Metastatic Colorectal Cancer

Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial

Study of Dato-DXd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03)

Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors

Resilience and Equity in Aging, Cancer, and Health (REACH)

A Study of ART0380 for the Treatment of Advanced or Metastatic Solid Tumors