NCT03576963

Guadecitabine and Nivolumab in Treating Refractory Metastatic Colorectal Cancer

A Phase Ib/II Study of Guadecitabine (SGI-110) Plus Nivolumab in Refractory CIMP+ Metastatic Colorectal Cancer

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University of Southern California · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase Ib/II trial studies the side effects and best dose of guadecitabine when given together with nivolumab and to see how well they work in treating participants with colorectal cancer that does not respond to treatment and has spread to other places in the body. Drugs used in chemotherapy, such as guadecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Giving guadecitabine and nivolumab may work better in treating participants with colorectal cancer.

Detailed description

PRIMARY OBJECTIVES: I. To determine the safety, tolerability, maximum tolerated dose (MTD)/recommended phase 2 dose (R2PD) of guadecitabine in combination with nivolumab in patients with refractory CpG island methylator phenotype (CIMP+) metastatic colorectal cancer. (Phase Ib Dose Escalation) II. To assess the overall response rate (ORR) in refractory CIMP+ metastatic colorectal cancer patients treated with guadecitabine and nivolumab. (Phase II Expansion) SECONDARY OBJECTIVES: I. To determine the incidence of adverse events (AEs) and serious adverse events (SAEs) of guadecitabine combined with nivolumab. (Phase Ib Dose Escalation) II. To assess progression-free (PFS) and overall survival (OS) in refractory CIMP+ metastatic colorectal cancer patients treated with guadecitabine and nivolumab. (Phase II Dose Expansion) EXPLORATORY OBJECTIVES: I. Characterize pre and post-treatment morphometric, proteomic and genomic profiles of circulating tumor cells using the high-definition single cell analysis (HD-SCA) platform. II. Determine associations between circulating cell-free tumor deoxyribonucleic acid (DNA), messenger ribonucleic acid (mRNA) expression, inflammatory T-cell and DNA methylation signatures, with response rate (RR), PFS, OS. III. Determine associations between tumor PD1/PDL1 expression with RR, PFS, OS. OUTLINE: This is a phase Ib, dose-escalation study of guadecitabine followed by a phase II study. Participants receive guadecitabine subcutaneously (SC) on days 1-5 and nivolumab intravenously (IV) over 2 hours on days 8 and 22. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity. After completion of study treatment, participants are followed up at 30 days and then every 2 months for 1 year.

Conditions

• Colorectal Adenocarcinoma
• CpG Island Methylator Phenotype
• Metastatic Microsatellite Stable Colorectal Carcinoma
• Refractory Colorectal Carcinoma
• Stage IV Colorectal Cancer AJCC v8
• Stage IVA Colorectal Cancer AJCC v8
• Stage IVB Colorectal Cancer AJCC v8
• Stage IVC Colorectal Cancer AJCC v8

Interventions

Type	Name	Description
DRUG	Guadecitabine	Given SC
BIOLOGICAL	Nivolumab	Given IV

Timeline

• Start date: 2020-01-30
• Primary completion: 2022-01-30
• Completion: 2023-01-30
• First posted: 2018-07-05
• Last updated: 2021-04-05

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study