iExosomes for metastatic pancreatic cancer with KRAS G12D mutation

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This early-phase dose-escalation trial gives intravenous mesenchymal stromal cell-derived exosomes loaded with siRNA against KRAS G12D (iExosomes) to patients with metastatic pancreatic ductal adenocarcinoma carrying the KRAS G12D mutation. Infusions are administered on days 1, 4, and 10 of a 14-day cycle for up to three cycles while doses are escalated to find the maximum tolerated dose and dose-limiting toxicities. Secondary endpoints include pharmacokinetics, overall response rate, disease control rate, progression-free survival, and overall survival, and exploratory analyses will measure cfDNA, serum exosomes, and tissue when available. Safety and early anti-tumor activity will guide whether this targeted delivery approach moves forward.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Where it's running

• M D Anderson Cancer Center
  Houston, Texas, United States Recruiting

Study contacts

• Principal investigator: Brandon Smaglo, MD — M.D. Anderson Cancer Center
• Study coordinator: Brandon Smaglo, MD
• Email: bgsmaglo@mdanderson.org
• Phone: (713) 745-8763

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.