Trials / Terminated

TerminatedNCT03844750

Preoperative Immunotherapy (Pembrolizumab) for Patients With Colorectal Cancer and Resectable Hepatic Metastases

A Phase II Study of Preoperative Immunotherapy in Patients With Colorectal Cancer and Resectable Hepatic Metastases

Status: Terminated
Phase: Phase 2
Study type: Interventional
Enrollment: 6 (actual)

Sponsor: Chloe Atreya, MD, PhD · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase II trials studies how well pembrolizumab and vactosertib work after standard of care chemotherapy in patients with colorectal cancer that has spread to the liver that can be removed by surgery (resectable hepatic metastases). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Vactosertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and vactosertib after standard of care chemotherapy, but before liver metastases surgery, may help shrink the cancer prior to surgery. This study also investigates pembrolizumab and vactosertib after liver metastases surgery, decrease the risk of the cancer recurring (coming back).

Detailed description

PRIMARY OBJECTIVE: I. To characterize the change in the populations of tumor infiltrating lymphocytes (TILs) induced by neoadjuvant pembrolizumab plus vactosertib in participants with metastatic colorectal cancer (mCRC). SECONDARY OBJECTIVES: I. To establish the safety/toxicity profile of pembrolizumab-based treatment in the perioperative setting for participants with colorectal cancer (CRC) with resectable hepatic metastases. II. To explore the efficacy of pembrolizumab plus vactosertib in participants with CRC with resectable hepatic metastases. EXPLORATORY OBJECTIVES: I. To determine the impact of pembrolizumab-based treatment on programmed death-ligand 1 (PD-L1) expression in tumor cells and tumor-infiltrating immune cells (TIICs), in participants with mCRC. II. To determine the change in T cell repertoire within the tumor and blood induced by neoadjuvant pembrolizumab-based treatment in participants with mCRC. III. To explore molecular profiles to identify potentially predictive biomarkers for participants with metastatic CRC treated with immunotherapy (including but not limited to microsatellite instability (MSI) testing). IV. To correlate change in TIICs, PD-L1 expression, and T cell repertoires as well as molecular profiles with response/resistance and toxicity. V. To identify immune response messenger ribonucleic acid (mRNA) expression analysis to derive signatures associated with tumor response. VI. To identify genomic mutations and gene copy aberrations associated with response and resistance to therapy. VII. To correlate changes in microbiome composition and diversity with diet and lifestyle factors. OUTLINE: Participants receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and vactosertib orally (PO) once a day (QD) for the first cycle 5 days a week for 2 weeks. Participants then undergo standard of care surgical removal of liver metastases approximately 2 weeks (minimum 1 week) after last dose of vactosertib. OPTIONAL ADJUVANT TREATMENT: After surgery, eligible participants may also receive pembrolizumab and vactosertib every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants who do not undergo optional adjuvant treatment are followed up at 14 days and then every 90 days for up to 1 year. Participants who undergo optional adjuvant treatment are followed up at 30 days and then every 90 days for up to 2 years.

Conditions

Interventions

Type	Name	Description
PROCEDURE	Hepatectomy	Undergo liver resection.
BIOLOGICAL	Pembrolizumab	Given IV
DRUG	Vactosertib	Given orally

Timeline

Start date: 2019-07-22
Primary completion: 2025-09-30
Completion: 2025-09-30
First posted: 2019-02-18
Last updated: 2025-12-31
Results posted: 2025-12-31

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT03844750. Inclusion in this directory is not an endorsement.