Minnelide Along With Abraxane Plus Gemcitabine in Patients With Metastatic Adenocarcinoma of the Pancreas

A Phase 1b, Open-Label, Safety, Pharmacokinetic, and Pharmacodynamic Study of an Anti-super-enhancer Minnelide Given Along With Abraxane Plus Gemcitabine in Patients With Metastatic Adenocarcinoma of the Pancreas

A Phase 1b, Open-Label, Safety, Pharmacokinetic, and Pharmacodynamic Study of an Anti-super-enhancer Minnelide Once a Day on Days 1 to 5, Days 8 to 12 and Days 15 to 19 Along with Abraxane Plus Gemcitabine in Patients with Metastatic Adenocarcinoma of the Pancreas

Study Overview

• Status: Recruiting
• Conditions: Metastatic Adenocarcinoma of the Pancreas
• Intervention / Treatment: Combination product: Minnelide

Detailed Description

Stressing the patient's pancreatic cancer by giving the anti-super-enhancer Minnelide to increase endoplasmic reticulum (ER) stress and improve the progression-free survival (PFS) when patients are treated with standard of care (SOC) nanoparticle albumin-bound (nab)-paclitaxel (Abraxane) plus gemcitabine.

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 1

Contacts and Locations

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

Study Locations

• Korea, Republic of
  • Soeul, Korea, Republic of, 135-710
    • Recruiting
    • Samsung Medical Center
    • Contact: Miae Jo, RN; Phone Number: +82-2-3410-6130; Email: miae41.jo@samsung.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• • Signed, written IRB-approved informed consent.

  • Patients diagnosed with histologically confirmed metastatic adenocarcinoma of the pancreas combined with adenocarcinoma and adenosquamous are allowed, but pure adenosquamous patients are excluded.
  • Disease progression while on FOLFIRINOX as first treatment.
  • Had no prior treatment with nab-paclitaxel (Abraxane) plus gemcitabine or single agent nab-paclitaxel or gemcitabine or in any other combinations.
  • Patient who has received prior or going to receive any killed vaccine including influenza, pneumococcal or COVID-19 during the study are allowed but any live vaccine like Herpes Zoster is not allowed. One or more metastatic tumours measurable on computed tomography (CT) scan per Response Evaluation Criteria in Solid Tumours (RECIST) V1.1 criteria excluding the primary pancreatic lesion.
  • Karnofsky performance ≥ 70%.
  • Life expectancy of at least 3 months, as determined by the Investigator.
  • Age ≥ 19 years.
  • A negative pregnancy test (if female).

  • Acceptable liver function as per below:

    • Bilirubin ≤ 1.5 × upper limit of normal (ULN)
    • Aspartate aminotransferase (AST), serum glutamic oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT), serum glutamic pyruvic transaminase (SGPT), and alkaline phosphatase (ALP) ≤ 2.5 × ULN (if liver metastases are present, then ≤ 5 × ULN is allowed).
    • Albumin ≥ 3.0 g/dL.

  • Acceptable renal function as per below:

    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 haematologic status:

    • Baseline absolute neutrophil counts ≥ 2000 cells/mm3.
    • Platelet count ≥ 100000 cells/mm3.
    • Haemoglobin ≥ 9 g/dL.
  • Urinalysis: No clinically significant abnormalities.

  • Acceptable coagulation status in the absence of therapeutic intent to anticoagulate:

    • Prothrombin time (PT) ≤ 1.5 × institutional ULN.
    • Partial thromboplastin time (PTT) ≤ 1.5 × institutional ULN.
    • International normalised ratio (INR) ≤ 1.5 × institutional ULN. Note: Abnormal lab values will be retested once within 2 weeks.

  • For men and women of childbearing potential, the use of effective contraceptive methods during the study. From last dose effective contraception is to be maintained as follows:

    • Men: 100 days from last dose of MinnelideTM.
    • Women of childbearing potential: 6 months from last dose of MinnelideTM.
  • For females, agree to the use of two physician-approved contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomised partner) while on study IP, and for 3 months following the last dose of IP.
  • Has negative serum pregnancy test (β-hCG) result at Screening.
  • For males, must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following IP discontinuation, even if he has undergone a successful vasectomy.

Exclusion Criteria:

• • New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischaemia on ECG.

  • Baseline QTc exceeding 470 msec (using the Bazett's formula) and/or patients receiving class 1A or class III antiarrhythmic agents. Note: If a single value of QTcB> 470 msec is observed which is not clinically significant as per the Investigator, triplicate ECGs should be performed and if the average QTcB ≤ 470 msec, then the patient can be included in the study.
  • Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
  • Pregnant or nursing women. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her PI immediately.
  • Treatment with radiation therapy (local therapy, non target lesion within 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 except for chronic hepatitis B or C patients with undetectable viral load.
  • Serious non-malignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.
  • Any other malignancy within 5 years prior to study drug administration, with the exception of adequately treated in-situ carcinoma of the cervix, uteri, or non-melanomatous skin cancer (all treatment of which should have been completed 6 months prior to enrollment).
  • Patient with a history or current evidence of brain metastasis or leptomeningeal disease.
  • Currently receiving any other investigational agent.
  • On a prohibited medication (clarithromycin, loperamide, ondansetron, poly (ADP) - ribose polymerase inhibitors, programmed cell death protein 1 inhibitors, and tyrosine kinase inhibitors or immunotherapeutics).

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 Study of Minnelide in Patients with Metastatic Adenocarcinoma of the Pancreas; This is an open-label, Phase 1b study of MinnelideTM given once a day on Days 1 to 5, Days 8 to12 and Days 15 to 19 in combination with SOC (nab-paclitaxel [Abraxane] plus gemcitabine). The study will be conducted in patients with disease progression while on FOLFIRINOX as first treatment and who have had no prior treatment with nab-paclitaxel (Abraxane) plus gemcitabine or single agent nab paclitaxel or gemcitabine or in any other combinations. The total number of treatment cycles administered will be dependent on drug tolerability by patient.

Combination product: Minnelide; Stressing the patient's pancreatic cancer by giving the anti super-enhancer Minnelide to increase endoplasmic reticulum (ER) stress and improve the progression-free survival (PFS) when patients are treated with standard of care (SOC) nanoparticle albumin-bound (nab)-paclitaxel (Abraxane) plus gemcitabine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the safety of Minnelide capsules when given in combination with SOC	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 in combination of gemcitabine and nab-paclitaxel compared to the incidence with gemcitabine and nab-paclitaxel.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pharmacokinetics of Minnelide and to determine the pharmacodynamics of GRP78	To determine the pharmacokinetics of Minnelide when given in combination with gemcitabine and nab-paclitaxel Plasma concentration data will be used to determine the following PK parameters: AUC Area under the concentration curve; Cmax Maximum plasma concentration; Tmax Time to maximum plasma concentration; t1/2 Terminal phase half life; CL/F Total body clearance; Vd/F Apparent volume of distribution; To determine the effects of Minnelide on the pharmacodynamics of GRP78	24 months

Collaborators and Investigators

• Sponsor: Minneamrita Therapeutics LLC
• Investigators: Principal Investigator: Joon Oh Park, MD, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: September 22, 2022
• First Submitted That Met QC Criteria: September 26, 2022
• First Posted (Actual): September 28, 2022

Study Record Updates

• Last Update Posted (Estimate): December 9, 2022
• Last Update Submitted That Met QC Criteria: December 8, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Pancreatic Cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; 14-O-phosphonooxymethyltriptolide disodium salt
• Other Study ID Numbers: Minnelide_ACP_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