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

Conditions: Advanced Cancer; Gastric Cancer; Breast Cancer; Pancreatic Cancer; Prostate Cancer Metastatic; Colo-rectal Cancer; Solid Tumor; Solid Carcinoma; Solid Carcinoma of Stomach; Cancer of Stomach

Summary: 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 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)

Keywords: metastatic