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
- Conditions
- Neoplasms
- Registration Number
- KCT0006519
- Lead Sponsor
- Samsung Medical Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 18
• Patients with histologically confirmed advanced gastric cancer
• Tumor progression after receiving standard/approved chemotherapy or where there is no approved therapy
• One or more metastatic tumors measurable per RECIST v1.1 Criteria
• Karnofsky performance = 70%
• Life expectancy of at least 3 months
• Age ³ 19 years
• Signed, written IRB-approved informed consent
• A negative pregnancy test (if female)
• Acceptable liver function:
o Bilirubin £ 1.5 times upper limit of normal
o 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)
o Albumin = 3.0 g/dL
• 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.
• Acceptable hematologic status:
o Granulocyte
? Monotherapy: ³ 1,500 cells/mm3
? Combination therapy with paclitaxel: ³
2,000 cells/mm3
o Platelet count ³ 100,000 (plt/mm3)
o Hemoglobin ³ 9 g/dL
• Urinalysis:
o No clinically significant abnormalities
• Acceptable coagulation status:
o PT = 1.5 times institutional ULN
o PTT = 1.5 times institutional ULN
• 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.
• 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: 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 untill 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.
• Treatment with radiation therapy (local therapy, nontarget lesion, 2 weeks), major surgery, chemotherapy, biological agents or investigational therapy within 3
weeks prior to study treatment.
• 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 4.3.2).
• Patients with biliary obstruction and/or biliary stent
(Regimen B only)
• 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
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of Minnelide™ Capsules when given alone or in combination with paclitaxel. ;To establish the dose of Minnelide™ Capsules recommended for future phase II protocol when given alone or in combination with paclitaxel.
- Secondary Outcome Measures
Name Time Method Biomarkers as applicable for gastric cancer, any tumor marker appropriate to the given cancer or that is known to be elevated in a given patient will be evaluated according the Investigator’s discretion, prior to every Cycle.;Serum HSP70 levels; PET Scans ;Evaluation of CT scans using Choi criteria