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NCT05900648 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 2022-0726NCI-2023-04464
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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

Conditions

Colorectal Cancer; Colon Cancer; Rectum Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  through study completion; an average of 1 year

Study Arms (1)

Regorafenib and XmAb20717

EXPERIMENTAL

Participants will receive regorafenib and XmAb20717 for up to 6 cycles (6 months). Participants will take regorafenib by mouth on Days 1-21 of each cycle. Participants will rest (not take regorafenib) on Days 21-28 of each cycle. Participants will also receive XmAb20717 by vein on Days 1 and 15 of each cycle. Each infusion should take about 60 minutes.

Drug: Regorafenib; Drug: XmAb20717

Interventions

Regorafenib DRUG

Given by PO

Also known as: BAY 73-4506

Regorafenib and XmAb20717

XmAb20717 DRUG

Given by (IV) vein

Regorafenib and XmAb20717

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological confirmation of CRC
• Post-R0 resection of stages II, III, or IV CRC and all planned adjuvant therapies have been completed
• No evidence of radiographic disease within 28 days (before or after) of a positive ctDNA assay
• 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)
• Adequate organ and marrow function as defined below:
• Absolute neutrophil count: ≥1,000/mcL
• Platelets: ≥100,000/mcL
• Total bilirubin ≤1.5 x the upper limit of normal (ULN). Total bilirubin (≤3 x ULN) is allowed if Gilbert's syndrome is documented.
• AST(SGOT)/ALT(SGPT): ≤3 × institutional ULN (≤5 x ULN for patients with liver involvement of their cancer).
• 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) ÷ \[72 x (serum creatinine in mg/dL)\] \[0.85 if female\]
• ECOG performance status (PS) of 0 or 1 (Appendix A)
• Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of regorafenib in these patients, children \<18 years of age are excluded from this study.
• Able to understand and is willing to sign a written informed consent document.
• Postmenopausal (no menses in greater than or equal to 12 consecutive months).
• History of hysterectomy or bilateral salpingo-oophorectomy.

You may not qualify if:

• 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
• Systemic therapy with immunosuppressive agents within 7 days or use of any investigational drug within 28 days before the start of trial treatment.
• Prior exposure to any immune checkpoint blockade agent or any other immunomodulatory agent used for antineoplastic therapy for mCRC.
• Previous malignant disease (other than the target malignancy to be investigated in this trial) within 3 years prior to study treatment initiation.
• Receipt of any organ transplantation, including allogeneic stem cell transplantation (exception: transplants that do not require immunosuppression, such as hair transplant).
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
• 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.
• 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.
• 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.
• Failure to recover from any other toxicity (other than immune-related toxicity) related to previous anticancer treatment to ≤ Grade 2.
• Receipt of a live-virus vaccine within 30 days prior to first dose of study drug (seasonal flu vaccines that do not contain live virus are permitted).
• Evidence of any serious bacterial viral (active HIV, HCV or HBV), parasitic, or systemic fungal infections within the 30 days prior to the first dose of study drug.
• Subject is pregnant or breast feeding or planning to become pregnant while enrolled in the study, up to the final EOT visit.
• History of (non-infectious) pneumonitis that required steroids, ongoing pneumonitis, or history of interstitial lung disease.
• Grade \> 3 proteinuria ( \> 3.5 g/24 hours)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Xencor, Inc.: collaborator
• Bayer: collaborator

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

regorafenib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Kanwal Raghav, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2023
• First Posted: June 12, 2023
• Study Start: May 17, 2023
• Primary Completion: February 9, 2024
• Study Completion: February 9, 2024
• Last Updated: April 29, 2024

Record last verified: 2024-04