IExosomes In Treating Participants With Metastatic Pancreas Cancer With KrasG12D Mutation

Study Overview

IExosomes in Treating Participants with Metastatic Pancreas Cancer with KrasG12D Mutation

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.

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.

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

2018-0126
NCI-2018-01441 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
2018-0126 (OTHER Identifier) (OTHER: M D Anderson Cancer Center)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2018-07-16	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2024-10-14
First Submitted that Met QC Criteria 2018-07-24	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2024-10-16
First Posted (ACTUAL) 2018-08-01	Results First Posted N/A	Last Verified 2024-10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
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. Participant	DRUG: Mesenchymal Stromal Cells-derived Exosomes with KRAS G12D siRNA Given IV

Participant Group/Arm

Intervention/Treatment

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. Participant

DRUG: Mesenchymal Stromal Cells-derived Exosomes with KRAS G12D siRNA

Given IV

Primary Outcome Measures	Measure Description	Time Frame
Maximum Tolerated Dose Determined by Dose Limiting Toxicity	Dose limiting toxicity graded according to the NCI CTCAE, Version 4.0	First 4 weeks of treatment
Minimal residual disease rate in high-risk patients	Will be modeled using logistic regression.	Up to 1 year
Overall survival (OS)	Estimated using the Kaplan-Meier product limit estimator.	Up to 1 year
Progression-free survival (PFS)	Estimated using Kaplan-Meier product limit estimator.	Up to 1 year

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Patients with histologically confirmed metastatic pancreatic ductal adenocarcinoma harboring KrasG12D mutation
Patients must have documented progression or stable disease on one or more lines of systemic therapy. If stable disease, patient must have completed at least 4 months of chemotherapy with cytotoxic therapy
KrasG12D mutation status will be informed from any previous routine molecular profiling (using commercial assays such as Foundation One, Caris, Oncomine or other) of tissue or blood. Additional KrasG12D mutation status may be confirmed using tissue biopsy or blood prior to enrolling into the trial
ECOG (Eastern Cooperative Oncology Group) performance status of 0-1
Absolute neutrophil count (ANC) more or equal to 1,500 cells/mm3
Platelets more or equal to 100,000/ul
Hemoglobin more than 9.0 g/dL
Total bilirubin between 1 and 1.5 mg/dL
AST (aspartate aminotransferase) and ALT (alanine transaminase) less than 2.5 x ULN (upper limit of normal)
Alkaline phosphatase less than 2.5 x ULN
Creatinine less than 1.5 gm/dL
In patients with known Gilbert's syndrome, direct bilirubin less or equal to 1.5 x ULN will be used as organ function criteria, instead of total bilirubin
Negative serum pregnancy test in women with childbearing potential (WOCBP) defined as not post-menopausal for 12 months or no previous surgical sterilization, within one week prior to initiation of treatment. WOCBP must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of study drug to minimize the risk of pregnancy. WOCBP must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of study drug to minimize the risk of pregnancy
A male subject of fathering potential must use an adequate method of contraception to avoid conception throughout the study and for up to 12 weeks after the last dose of study drug to minimize the risk of pregnancy. If the partner is pregnant or breastfeeding, the subject must use a condom
Patients must sign an informed consent and authorization indicating that they are aware of the investigational nature of this study and the known risks involved

Concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study such as unstable angina, myocardial infarction within 6 months, unstable symptomatic arrhythmia, uncontrolled diabetes, serious active or uncontrolled infection
Pregnancy (positive pregnancy test) or lactation
Known CNS (central nervous system) disease, except for treated brain metastasis. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (magnetic resonance imaging-MRI or computerized tomography-CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; gamma knife, linear accelerator [LINAC], or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to day 1 will be excluded

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Brandon Smaglo, MD, M.D. Anderson Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Tang M, Chen Y, Li B, Sugimoto H, Yang S, Yang C, LeBleu VS, McAndrews KM, Kalluri R. Therapeutic targeting of STAT3 with small interference RNAs and antisense oligonucleotides embedded exosomes in liver fibrosis. FASEB J. 2021 May;35(5):e21557. doi: 10.1096/fj.202002777RR.

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Clinical Trial Record