Minnelide™ Capsules Alone and in Combination With Paclitaxel in Advanced Gastric Cancer

Inclusion Criteria:

• Patients with histologically confirmed advanced gastric cancer
• Tumor progression after receiving standard/approved chemotherapy or where thereis 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 ofnormal (if liver metastases are present, then 5 x ULN is allowed)
• Albumin ≥ 3.0 g/dL
• Acceptable renal function: o Serum creatinine within normal limits, OR calculated creatinine clearance ³ 60mL/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: o 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 adequatecontraception For men and women of child-producing potential, the use ofeffective contraceptive methods during the study and until 90 days after the lastdose of IP for men or until 6 months after the last dose of IP for women or 6months 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 withinthe past 6 months, unstable arrhythmia, or evidence of ischemia on ECG

• Baseline QTc exceeding 470 msec (using the Bazett's formula) and/or patients receivingclass 1A or class III antiarrhythmic agents.
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemictherapy.
• Pregnant or nursing women. NOTE: For men and women of child-producing potential, theuse of effective contraceptive methods during the study and until 90 days after thelast dose of IP for men or until 6 months after the last dose of IP for women or 6months after the last dose of IP with paclitaxel for both men and women. Should awoman 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), majorsurgery, chemotherapy, biological agents or investigational therapy within 3 weeksprior 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 otherconditions) that could compromise protocol objectives in the opinion of theinvestigator 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 containingCremophor® EL (eg, cyclosporin for injection concentrate and teniposide for injectionconcentrate). • Patient with baseline ANC<1500/mm3