RecruitingPhase 1Phase 2NCT03608631

iExosomes in Treating Participants With Metastatic Pancreas Cancer With KrasG12D Mutation

Phase I Study of Mesenchymal Stromal Cells-Derived Exosomes With KrasG12D siRNA for Metastatic Pancreas Cancer Patients Harboring KrasG12D Mutation

Sponsor

M.D. Anderson Cancer Center

Enrollment

28 participants

Start Date

Jan 27, 2021

Study Type

INTERVENTIONAL

Conditions

Stage IV Pancreatic Cancer AJCC v8 Pancreatic Ductal Adenocarcinoma Metastatic Pancreatic Adenocarcinoma KRAS NP_004976.2:p.G12D

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria15

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 Criteria3

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