A Phase 1, Multi-Center, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Minnelide™ Capsules Given Alone or in Combination With Protein-Bound Paclitaxel in Patients With Advanced Solid Tumors

Inclusion Criteria

• Inclusion: - Patients with histologically confirmed advanced solid tumors (regimen A), breast or pancreas (regimen B), or gastric cancer (regimen C) - Tumor progression after receiving standard/approved chemotherapy or where there is no approved therapy - Prior treatment with protein-bound paclitaxel allowed if it has been six months since received or progressed on protein-bound paclitaxel and plan to continue to receive protein-bound paclitaxel with MinnelideTM Capsules - One or more metastatic tumors measurable per RECIST v1.1 Criteria - Karnofsky performance ≥ 70% - Life expectancy of at least 3 months - Age ≥ 18 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: o Serum creatinine within normal limits, OR calculated creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. - Acceptable hematologic status: - Granulocyte ≥ 1500 cells/mm3 - Platelet count ≥ 100,000 (plt/mm3) - Hemoglobin ≥ 9 g/dL - Urinalysis: o No clinically significant abnormalities - Acceptable coagulation status: - PT ≤ 1.5 times institutional ULN - PTT ≤ 1.5 times institutional ULN - For men and women of child-producing potential, the use of effective contraceptive methods during the study 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: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. 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, surgery, chemotherapy, or investigational therapy within one month prior to study entry (6 weeks for nitrosoureas or Mitomycin C). - 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 4.4.2). - Patients with biliary obstruction and/or biliary stent (Regimen B only)