AzTrials
AzTrials

KRAS NP_004976.2:p.G12DPhase 1/2NCT03608631

iExosomes in Treating Participants With Metastatic Pancreas Cancer With KrasG12D Mutation

A Phase 1/2 study testing Mesenchymal Stromal Cells-derived Exosomes with KRAS G12D siRNA in people with KRAS NP_004976.2:p.G12D and Metastatic Pancreatic Adenocarcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Mesenchymal Stromal Cells-derived Exosomes with KRAS G12D siRNA
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
1 siteUnited States
Study dates
27 Jan 2021to 30 Apr 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 15Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Brandon Smaglo, MD contact

(713) 745-8763

bgsmaglo@mdanderson.org

United States1 site, 1 recruiting

  • M D Anderson Cancer Center

    Houston, Texas, 77030

    Brandon Smaglo, MD, 713-792-2828, spant@mdanderson.org

    Brandon Smaglo

    Recruiting

Other trials in United States

About this study

Official title: Phase I Study of Mesenchymal Stromal Cells-Derived Exosomes With KrasG12D siRNA for Metastatic Pancreas Cancer Patients Harboring 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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
Mesenchymal Stromal Cells-derived Exosomes with KRAS G12D siRNA
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Mesenchymal Stromal Cells-derived Exosomes with KRAS G12D siRNADrug

    Also called MSC-derived Exosomes with KrasG12D siRNA (SY); KrasG12D siRNA-loaded Mesenchymal Stromal Cells-derived Exosomes (SY)

    Given IV

Study groups in NCT03608631
Study groupRoleWhat they receive
Treatment (iExosomes)ExperimentalParticipants 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.
Receives: Drug: Mesenchymal Stromal Cells-derived Exosomes with KRAS G12D siRNA

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose Determined by Dose Limiting Toxicity

    Dose limiting toxicity graded according to the NCI CTCAE, Version 4.0

    Measured: First 4 weeks of treatment

  2. Minimal residual disease rate in high-risk patients

    Will be modeled using logistic regression.

    Measured: Up to 1 year

  3. Overall survival (OS)

    Estimated using the Kaplan-Meier product limit estimator.

    Measured: Up to 1 year

  4. Progression-free survival (PFS)

    Estimated using Kaplan-Meier product limit estimator.

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Aug 2018
  2. Study start27 Jan 2021
  3. Primary completion30 Apr 2027 (estimated)
  4. Study completion30 Apr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03608631
Sponsor's protocol ID
2018-0126
Other IDs
NCI-2018-01441, 2018-0126
Status last verified
Sep 2026
First submitted
16 Jul 2018
Last updated
4 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 37781539

  • 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.

    PubMed 33855751

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Mesenchymal Stromal Cells-derived Exosomes with KRAS G12D siRNA in people with KRAS NP_004976.2:p.G12D and Metastatic Pancreatic Adenocarcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Brandon Smaglo, MD ((713) 745-8763, bgsmaglo@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose Determined by Dose Limiting Toxicity (time frame: First 4 weeks of treatment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03608631, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2026.

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