Overview

A Phase 1, Open-label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of Minnelide™ Capsules given alone or in combination with paclitaxel in patients with Advanced Gastric Cancer.

Eligibility

Inclusion Criteria:

• Patients with histologically confirmed advanced gastric cancer
  • Tumor progression after receiving standard/approved chemotherapy or where there is no approved therapy
  • One or more metastatic tumors measurable per RECIST v1.1 Criteria
  • Karnofsky performance ≥ 70%
  • Life expectancy of at least 3 months
  • Age ³ 19 years
  • Signed, written IRB-approved informed consent
  • A negative pregnancy test (if female)
  • Acceptable liver function:
    • Bilirubin 1.5 times upper limit of normal
    • AST (SGOT), ALT (SGPT) and Alkaline phosphatase 2.5 times upper limit of normal (if liver metastases are present, then 5 x ULN is allowed)
    • Albumin ≥ 3.0 g/dL
  • Acceptable renal function:
    • Serum creatinine within normal limits, OR calculated creatinine clearance ³ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
  • Acceptable hematologic status:
    • Granulocyte
      • Monotherapy: ³ 1,500 cells/mm3
      • Combination therapy with paclitaxel: ³ 2,000cells/mm3 Platelet count ³ 100,000 (plt/mm3)
    • Hemoglobin ³ 9 g/dL
  • Urinalysis:
    • No clinically significant abnormalities
  • Acceptable coagulation status:
    • PT ≤ 1.5 times institutional ULN
    • PTT ≤ 1.5 times institutional ULN
  • Women of child- bearing potential and men must agree to use adequate

    contraception For men and women of child-producing potential, the use of effective contraceptive methods during the study and until 90 days after the last dose of IP for men or until 6 months after the last dose of IP for women or 6 months after the last dose of IP with paclitaxel for both men and women.

Exclusion Criteria:

        New York Heart Association Class III or IV, cardiac disease, myocardial infarction within
        the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG
          -  Baseline QTc exceeding 470 msec (using the Bazett's formula) and/or patients receiving
             class 1A or class III antiarrhythmic agents.
          -  Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
             therapy.
          -  Pregnant or nursing women. NOTE: For men and women of child-producing potential, the
             use of effective contraceptive methods during the study and until 90 days after the
             last dose of IP for men or until 6 months after the last dose of IP for women or 6
             months after the last dose of IP with paclitaxel for both men and women. Should a
             woman become pregnant or suspect she is pregnant while participating in this study,
             she should inform her treating physician immediately.
          -  Treatment with radiation therapy (local therapy, non-target lesion, 2 weeks), major
             surgery, chemotherapy, biological agents or investigational therapy within 3 weeks
             prior to study treatment.
          -  Unwillingness or inability to comply with procedures required in this protocol
          -  Known infection with HIV, hepatitis B, or hepatitis C
          -  Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other
             conditions) that could compromise protocol objectives in the opinion of the
             investigator and/or the sponsor
          -  Patients who are currently receiving any other investigational agent
          -  Patients who are on a prohibited medication (section 4.3.2).
          -  Patients with biliary obstruction and/or biliary stent (Regimen B only)
          -  Patients with a history of severe hypersensitivity reactions to products containing
             Cremophor® EL (eg, cyclosporin for injection concentrate and teniposide for injection
             concentrate). • Patient with baseline ANC<1500/mm3