NCT03608631

Brief 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
28

participants targeted

Target at P25-P50 for phase_1

Timeline
12mo left

Started Jan 2021

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress84%
Jan 2021Apr 2027

First Submitted

Initial submission to the registry

July 16, 2018

Completed
16 days until next milestone

First Posted

Study publicly available on registry

August 1, 2018

Completed
2.5 years until next milestone

Study Start

First participant enrolled

January 27, 2021

Completed
6.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 30, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 30, 2027

Last Updated

November 26, 2025

Status Verified

November 1, 2025

Enrollment Period

6.3 years

First QC Date

July 16, 2018

Last Update Submit

November 20, 2025

Conditions

KRAS NP_004976.2:p.G12DPancreatic Ductal AdenocarcinomaStage IV Pancreatic Cancer AJCC v8Metastatic Pancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (4)

  • 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

Study Arms (1)

Treatment (iExosomes)

EXPERIMENTAL

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

Interventions

Mesenchymal Stromal Cells-derived Exosomes with KRAS G12D siRNADRUG

Given IV

Also known as: MSC-derived Exosomes with KrasG12D siRNA (SY); KrasG12D siRNA-loaded Mesenchymal Stromal Cells-derived Exosomes (SY)
Treatment (iExosomes)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (2)

  • Sall IM, Flaviu TA. Plant and mammalian-derived extracellular vesicles: a new therapeutic approach for the future. Front Bioeng Biotechnol. 2023 Sep 13;11:1215650. doi: 10.3389/fbioe.2023.1215650. eCollection 2023.

    PMID: 37781539DERIVED

  • 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.

    PMID: 33855751DERIVED

Related Links

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsEndocrine Gland NeoplasmsDigestive System DiseasesPancreatic DiseasesEndocrine System Diseases

Study Officials

  • Brandon Smaglo, MD

    M.D. Anderson Cancer Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Brandon Smaglo, MD

CONTACT

(713) 745-8763bgsmaglo@mdanderson.org

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 16, 2018

First Posted

August 1, 2018

Study Start

January 27, 2021

Primary Completion (Estimated)

April 30, 2027

Study Completion (Estimated)

April 30, 2027

Last Updated

November 26, 2025

Record last verified: 2025-11

Locations

US(1)