NCT03608631

iExosomes in Treating Participants With Metastatic Pancreas Cancer With KrasG12D Mutation

Phase I Study of Mesenchymal Stromal Cells-Derived Exosomes With KrasG12D siRNA for Metastatic Pancreas Cancer Patients Harboring KrasG12D Mutation

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 28 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the best dose and side effects of mesenchymal stromal cells-derived exosomes with KrasG12D siRNA (iExosomes) in treating participants with pancreatic cancer with KrasG12D mutation that has spread to other places in the body. iExosomes may work better at treating pancreatic cancer.

Detailed description

PRIMARY OBJECTIVES: I. To identify the maximum tolerated dose (MTD) of mesenchymal stem cell (MSC)-derived exosomes loaded with small interference RNA (siRNA) against KrasG12D (iExosomes) in metastatic pancreatic ductal adenocarcinoma (PDAC) patients with KrasG12D mutation. II. To identify the dose-limiting toxicities (DLT) of mesenchymal stem cell (MSC)-derived exosomes loaded with siRNA against KrasG12D (iExosomes) in metastatic PDAC patients with KrasG12D mutation. SECONDARY OBJECTIVES: I. Evaluate the pharmacokinetic profile of iExosomes. II. Assess the overall response rate of iExosomes in the chosen patient population. III. Assess the disease control rate (partial response + stable disease) with therapy. IV. Determine median progression-free survival (PFS) with this treatment. V. Determine the median overall survival (OS) with this treatment. EXPLORATORY OBJECTIVES: I. Evaluate optional tissue collection and serum-derived exosomes and circulating-free deoxyribonucleic acid (DNA) (cfDNA) for detection of DNA and ribonucleic acid (RNA) showing KrasG12D sequence; evaluate DNA and RNA showing KrasG12D sequence in optional tissue collection. II. Evaluate the siRNA content in blood and optional tissue collection. OUTLINE: This is a dose-escalation study. Participants receive mesenchymal stromal cells-derived exosomes with KrasG12D siRNA intravenously (IV) over 15-20 minutes on days 1, 4, and 10. Treatment repeats every 14 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Participants who respond may continue 3 additional courses. After completion of study treatment, participants are followed up at 30 days, then every 3 months for up to 1 year.

Conditions

• KRAS NP_004976.2:p.G12D
• Metastatic Pancreatic Adenocarcinoma
• Pancreatic Ductal Adenocarcinoma
• Stage IV Pancreatic Cancer AJCC v8

Interventions

Type	Name	Description
DRUG	Mesenchymal Stromal Cells-derived Exosomes with KRAS G12D siRNA	Given IV

Timeline

• Start date: 2021-01-27
• Primary completion: 2027-04-30
• Completion: 2027-04-30
• First posted: 2018-08-01
• Last updated: 2025-11-26

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study