Overview
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
Eligibility
- Inclusion
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- 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:
- 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:
- 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)