Minnelide™ Capsules Alone and in Combination With Paclitaxel in Advanced Gastric Cancer

Minneamrita Therapeutics

Status and phase

Enrolling

Phase 1

Conditions

Gastric Cancer

Treatments

Drug: Minnelide

Study type

Interventional

Funder types

Industry

Identifiers

NCT05566834

Minnelide GC 101

Details and patient eligibility

About

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.

Full 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.

Enrollment

36 estimated patients

Sex

All

Ages

19+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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:
  - 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 ³ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
- Acceptable hematologic status:
  - Granulocyte
    - Monotherapy: ³ 1,500 cells/mm3
    - Combination therapy with paclitaxel: ³ 2,000cells/mm3 Platelet count ³ 100,000 (plt/mm3)
  - Hemoglobin ³ 9 g/dL
- Urinalysis:
  
  o No clinically significant abnormalities
- Acceptable coagulation status:
  - PT ≤ 1.5 times institutional ULN
  - 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.

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: 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.
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.
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