iExosomes in Treating Participants With Metastatic Pancreas Cancer With KrasG12D Mutation
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|ClinicalTrials.gov Identifier: NCT03608631|
Recruitment Status : Recruiting
First Posted : August 1, 2018
Last Update Posted : April 26, 2022
|Condition or disease||Intervention/treatment||Phase|
|KRAS NP_004976.2:p.G12D Metastatic Pancreatic Adenocarcinoma Pancreatic Ductal Adenocarcinoma Stage IV Pancreatic Cancer AJCC v8||Drug: Mesenchymal Stromal Cells-derived Exosomes with KRAS G12D siRNA||Phase 1|
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.
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||28 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of Mesenchymal Stromal Cells-Derived Exosomes With KrasG12D siRNA for Metastatic Pancreas Cancer Patients Harboring KrasG12D Mutation|
|Actual Study Start Date :||January 27, 2021|
|Estimated Primary Completion Date :||March 31, 2023|
|Estimated Study Completion Date :||March 31, 2023|
Experimental: Treatment (iExosomes)
Participants receive mesenchymal stromal cells-derived exosomes with KrasG12D siRNA 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.
Drug: Mesenchymal Stromal Cells-derived Exosomes with KRAS G12D siRNA
Other Name: MSC-derived Exosomes with KrasG12D siRNA (SY); KrasG12D siRNA-loaded Mesenchymal Stromal Cells-derived Exosomes (SY)
- Maximum Tolerated Dose Determined by Dose Limiting Toxicity [ Time Frame: First 4 weeks of treatment ]Dose limiting toxicity graded according to the NCI CTCAE, Version 4.0
- Minimal residual disease rate in high-risk patients [ Time Frame: Up to 1 year ]Will be modeled using logistic regression.
- Overall survival (OS) [ Time Frame: Up to 1 year ]Estimated using the Kaplan-Meier product limit estimator.
- Progression-free survival (PFS) [ Time Frame: Up to 1 year ]Estimated using Kaplan-Meier product limit estimator.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03608631
|Contact: Brandon Smaglo, MD||(713) firstname.lastname@example.org|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Brandon Smaglo, MD 713-792-2828 email@example.com|
|Principal Investigator: Brandon Smaglo|
|Principal Investigator:||Brandon Smaglo, MD||M.D. Anderson Cancer Center|