Minnelide™ Capsules Alone and in Combination With Paclitaxel in Advanced Gastric Cancer
Study Details
Study Description
Brief Summary
A Phase 1, Open-label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of Minnelide™ Capsules given alone or in combination with paclitaxel in patients with Advanced Gastric Cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
Minnelide™ is a water soluble disodium salt variant of triptolide, a diterpenoid, an HSP70 inhibitor. Studies using orthotopic pancreatic cancer cell lines and human xenograft transplants demonstrate that Minnelide™ prevents tumor progression, increases survival, and causes tumor regression.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Open-label, dose-escalation, safety, Pharmacodynamic, pharmacokinetic study. One |
Drug: Minnelide
at the MTD dose level established for monotherapy or combination to confirm safety. With a sample of 12 patients, the probability is > 80% that a serious adverse event with at least a 16% incidence will be detected.
|
Outcome Measures
Primary Outcome Measures
- To determine any increase of treatment emergent adverse events when Minnelide capsules are given in combination with paclitaxel. [24 months]
To observe any increase in the number of patients that experience Grade 4 neutropenia lasting ≥ 5 days or Grade 3 or 4 neutropenia with fever and/or infection; Grade 4 thrombocytopenia (or Grade 3 with bleeding); Grade 3 or 4 treatment-related non-hematological toxicity (Grade 3 nausea, vomiting or diarrhea that last > 72 hours despite maximal treatment when Minnelide is given alone and in combination with paclitaxel compared to the incidence with gemcitabine and nab-paclitaxel.
Secondary Outcome Measures
- Pharmacokinetics of Minnelide when given with paclitaxel [24 months]
Area under the concentration curve (AUC) will be determine the exposure of Minnelide
- Plasma levels of Minnelide when given with paclitaxel [24 months]
Maximum plasma concentration (Cmax) will be measured to determine the effect of Minnelide when given with paclitaxel
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients with histologically confirmed advanced gastric cancer
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Tumor progression after receiving standard/approved chemotherapy or where there is no approved therapy
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One or more metastatic tumors measurable per RECIST v1.1 Criteria
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Karnofsky performance ≥ 70%
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Life expectancy of at least 3 months
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Age ³ 19 years
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Signed, written IRB-approved informed consent
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A negative pregnancy test (if female)
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Acceptable liver function:
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Bilirubin 1.5 times upper limit of normal
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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)
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Albumin ≥ 3.0 g/dL
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Acceptable renal function:
o Serum creatinine within normal limits, OR calculated creatinine clearance ³ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
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Acceptable hematologic status:
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Granulocyte
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Monotherapy: ³ 1,500 cells/mm3
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Combination therapy with paclitaxel: ³ 2,000cells/mm3 Platelet count ³ 100,000 (plt/mm3)
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Hemoglobin ³ 9 g/dL
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Urinalysis:
o No clinically significant abnormalities
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Acceptable coagulation status:
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PT ≤ 1.5 times institutional ULN
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PTT ≤ 1.5 times institutional ULN
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Women of child- bearing potential and men must agree to use adequate contraception For men and women of child-producing potential, the use of effective contraceptive methods during the study and until 90 days after the last dose of IP for men or until 6 months after the last dose of IP for women or 6 months after the last dose of IP with paclitaxel for both men and women.
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
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Baseline QTc exceeding 470 msec (using the Bazett's formula) and/or patients receiving class 1A or class III antiarrhythmic agents.
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Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
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Pregnant or nursing women. NOTE: For men and women of child-producing potential, the use of effective contraceptive methods during the study and until 90 days after the last dose of IP for men or until 6 months after the last dose of IP for women or 6 months after the last dose of IP with paclitaxel for both men and women. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
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Treatment with radiation therapy (local therapy, non-target lesion, 2 weeks), major surgery, chemotherapy, biological agents or investigational therapy within 3 weeks prior to study treatment.
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Unwillingness or inability to comply with procedures required in this protocol
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Known infection with HIV, hepatitis B, or hepatitis C
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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
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Patients who are currently receiving any other investigational agent
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Patients who are on a prohibited medication (section 4.3.2).
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Patients with biliary obstruction and/or biliary stent (Regimen B only)
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Patients with a history of severe hypersensitivity reactions to products containing Cremophor® EL (eg, cyclosporin for injection concentrate and teniposide for injection concentrate). • Patient with baseline ANC<1500/mm3
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Samsung Medical Center | Soeul | Korea, Republic of | 135-710 |
Sponsors and Collaborators
- Minneamrita Therapeutics LLC
Investigators
- Study Director: Mohana Velagapudi, Minneamrita Therapeutics LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Minnelide GC 101