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

Stage IV Colorectal Cancer AJCC v8 Clinical Trial

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

Status Recruiting

Clinical Trial 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).

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To characterize the change in the populations of tumor infiltrating lymphocytes (TILs) induced by neoadjuvant pembrolizumab plus vactosertib in patients with metastatic colorectal cancer (mCRC).

SECONDARY OBJECTIVES:

I. To establish the safety/toxicity profile of pembrolizumab-based treatment in the perioperative setting for patients with colorectal cancer (CRC) with resectable hepatic metastases.

II. To explore the efficacy of pembrolizumab plus vactosertib in patients with CRC with resectable hepatic metastases.

EXPLORATORY OBJECTIVES:

I. To determine the impact of pembrolizumab-based treatment on PD-L1 expression in tumor cells and tumor-infiltrating immune cells (TIICs), in patients with mCRC.

II. To determine the change in T cell repertoire within the tumor and blood induced by neoadjuvant pembrolizumab-based treatment in patients with mCRC.

III. To explore molecular profiles to identify potentially predictive biomarkers for patients with metastatic CRC treated with immunotherapy (including but not limited to microsatellite instability (MSI) testing).

IV. To correlate change in TIICs, PDL-1 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:

Patients 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 and twice daily (BID) 5 days a week for cycle 2 and greater followed by a 2-day resting period for 2 weeks in the absence of disease progression or unacceptable toxicity. Patients 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 patients 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, patients who do not undergo optional adjuvant treatment are followed up at 14 days and then every 90 days for up to 1 year. Patients who undergo optional adjuvant treatment are followed up at 30 days and then every 90 days for up to 2 years. ;

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Malignant Neoplasm in the Liver
• Neoplasm Metastasis
• Neoplasms
• Stage IV Colorectal Cancer AJCC v8
• Stage IVA Colorectal Cancer AJCC v8
• Stage IVB Colorectal Cancer AJCC v8
• Stage IVC Colorectal Cancer AJCC v8

• NCT number: NCT03844750
• Study type: Interventional
• Source: University of California, San Francisco
• Contact: UCSF HDFCCC Cancer Immunotherapy Program (CIP)
• Phone: (877) 827-3222
• Email: HDFCCC.CIP@ucsf.edu
• Status: Recruiting
• Phase: Phase 2
• Start date: July 22, 2019
• Completion date: June 30, 2024