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

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

A Phase I, Multicenter, Open-label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of Minnelide™Capsules given daily for 21 days followed by 7 days off schedule in patients with Advanced Solid Tumors

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)