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

Study Overview
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Brief Summary
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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

Official Title
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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
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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

Intervention / Treatment
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* Drug: Minnelide™Capsules


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regimen A (monotherapy)<br>Minnelide™ Capsules will be given as a single agent orally once daily x 21 days followed by a 7-day off schedule. One cycle will equal 28 days. MinnelideTM Capsules should be given with the patient in a fasting state. | Drug: Minnelide™Capsules<br>* Minnelide™ is a water soluble disodium salt variant of triptolide an heat shock protein (HSP) inhibitor.<br>|
| Experimental: Regimen B (combination)<br>MinnelideTM Capsules will be given orally once daily x 21 days in combination with protein-bound paclitaxel given intravenously on days 1, 8 and 15 in patients with pancreas and breast cancer. One cycle will equal 28 days. MinnelideTM Capsules should be given with the patient in a fasting state. | Drug: Minnelide™Capsules<br>* Minnelide™ is a water soluble disodium salt variant of triptolide an heat shock protein (HSP) inhibitor.<br>|
| Experimental: Regimen C (monotherapy in Gastric Cancer)<br>Minnelide™ Capsules will be given as a single agent orally once daily x 21 days followed by a 7-day rest period. One cycle will equal 28 days. Minnelide™ Capsules should be given with the patient in a fasting state. | Drug: Minnelide™Capsules<br>* Minnelide™ is a water soluble disodium salt variant of triptolide an heat shock protein (HSP) inhibitor.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Related Adverse Events | as assessed by CTCAE V4 .03 | 24 months | 
| Anti-tumor activity | RECIST 1.1 | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic