Clinical Trials /

iExosomes in Treating Participants With Metastatic Pancreas Cancer With KrasG12D Mutation

NCT03608631

Description:

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.

Related Conditions:
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: iExosomes in Treating Participants With Metastatic Pancreas Cancer With KrasG12D Mutation
  • Official Title: Phase I Study of Mesenchymal Stromal Cells-Derived Exosomes With KrasG12D siRNA for Metastatic Pancreas Cancer Patients Harboring KrasG12D Mutation

Clinical Trial IDs

  • ORG STUDY ID: 2018-0126
  • SECONDARY ID: NCI-2018-01441
  • SECONDARY ID: 2018-0126
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03608631

Conditions

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

Interventions

DrugSynonymsArms
Mesenchymal Stromal Cells-derived Exosomes with KRAS G12D siRNAMSC-derived Exosomes with KrasG12D siRNA (SY); KrasG12D siRNA-loaded Mesenchymal Stromal Cells-derived Exosomes (SY)Treatment (iExosomes)

Purpose

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.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
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.
  • Mesenchymal Stromal Cells-derived Exosomes with KRAS G12D siRNA

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose Determined by Dose Limiting Toxicity
Time Frame:First 4 weeks of treatment
Safety Issue:
Description:Dose limiting toxicity graded according to the NCI CTCAE, Version 4.0

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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