NCT03290937

Utomilumab, Cetuximab, and Irinotecan Hydrochloride in Treating Patients With Metastatic Colorectal Cancer

Phase I Clinical Trial Evaluating the Safety and Response With PF-05082566, Cetuximab, and Irinotecan in Patients With Advanced Colorectal Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 16 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the best dose and side effects of irinotecan hydrochloride when given with utomilumab and cetuximab in treating patients with colorectal cancer that has spread to other places in the body (metastatic). Monoclonal antibodies, such as utomilumab and cetuximab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as irinotecan hydrochloride, 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. Giving utomilumab, cetuximab, and irinotecan hydrochloride may work better in treating patients with colorectal cancer.

Detailed description

PRIMARY OBJECTIVES: I. To evaluate maximal tolerated dose (MTD), and recommended phase 2 dose (RP2D) of the combination of utomilumab (PF-05082566), cetuximab and irinotecan hydrochloride (irinotecan) (PCI) in patients with metastatic colorectal cancer refractory to standard therapy. (Dose escalation) II. To determine the antitumor activity overall response rate (ORR) by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) of the study regimen specifically in patients with advanced colorectal cancer who are RAS-RAF wild type (WT) (Arm A) or RAS mutant (Arm B). (Dose expansion) SECONDARY OBJECTIVES: I. To evaluate overall safety profile. II. To evaluate the anti-tumor activity. III. To evaluate pharmacodynamics (PD) biomarkers expressed by peripheral blood mononuclear cells (PBMC) and tissue samples. IV. To characterize serum biomarkers linked to immunomodulation and cytokine release. V. To assess markers of T and natural killer (NK) cell phenotype (such as CD3, CD4, CD8, FoxP3, CD14, CD33, CCR7, CD45RO, CD16, CD56, CD69, CD25, or VCAM1), TNF alpha, IFN gamma, IL10, IL-8, IL-6, IL-4, IL-2, IL-1b, or IL-12p70, CD127, Ki67, eomesodermin, KLRG1, CD14, CD33, human leukocyte antigen- D related (HLA-DR), CD16, CD56, granzyme B, CD68, PD-1, CD11c, sCD137, and 4-1BB. OUTLINE: This is a dose escalation study of irinotecan hydrochloride. Patients receive irinotecan hydrochloride intravenously (IV) over 90 minutes and cetuximab IV over 1-2 hours on days 1 and 15, and utomilumab IV over 1 hour on day 2. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months.

Conditions

• Metastatic 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
BIOLOGICAL	Cetuximab	Given IV
DRUG	Irinotecan Hydrochloride	Given IV
OTHER	Pharmacodynamic Study	Correlative studies
BIOLOGICAL	Utomilumab	Given IV

Timeline

• Start date: 2017-12-27
• Primary completion: 2025-12-30
• Completion: 2025-12-30
• First posted: 2017-09-25
• Last updated: 2026-01-06

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study