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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: Minnelide

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 Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Mohana Velagapudi, MD; Phone Number: 3092693132; Email: mvelagapudi@minneamrita.com

Study Locations

• Korea, Republic of
  • Soeul, Korea, Republic of, 135-710
    • Recruiting
    • Samsung Medical Center
    • Contact: EUNKYUNG Park, RN; Phone Number: +82-2-2008-4390; Email: ekek.park@samsung.com
    • Principal Investigator: Jeeyun Lee, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine any increase of treatment emergent adverse events when Minnelide capsules are given in combination with paclitaxel.	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.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of Minnelide when given with paclitaxel	Area under the concentration curve (AUC) will be determine the exposure of Minnelide	24 months
Plasma levels of Minnelide when given with paclitaxel	Maximum plasma concentration (Cmax) will be measured to determine the effect of Minnelide when given with paclitaxel	24 months

Collaborators and Investigators

• Sponsor: Minneamrita Therapeutics LLC
• Investigators: Study Director: Mohana Velagapudi, Minneamrita Therapeutics LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2020
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: September 22, 2022
• First Submitted That Met QC Criteria: September 30, 2022
• First Posted (Actual): October 4, 2022

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Gastric Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; 14-O-phosphonooxymethyltriptolide disodium salt
• Other Study ID Numbers: Minnelide GC 101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No