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

NCT05557851 | Unknown Phase 1 DMC

• 1 other identifier: Minnelide_ACP_101
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Metastatic Adenocarcinoma of the Pancreas

Keywords

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• pharmacokinetics of Minnelide and to determine the pharmacodynamics of GRP78

  24 months

Study Arms (1)

Open Label Study of Minnelide in Patients with Metastatic Adenocarcinoma of the Pancreas

EXPERIMENTAL

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

Interventions

Minnelide COMBINATION_PRODUCT

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.

Open Label Study of Minnelide in Patients with Metastatic Adenocarcinoma of the Pancreas

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Minneamrita Therapeutics LLC: lead

Study Sites (1)

Samsung Medical Center

Soeul, 135-710, South Korea

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

14-O-phosphonooxymethyltriptolide disodium salt

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Joon Oh Park, MD

  Samsung Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mohana Velagapudi

CONTACT

3092693132; mvelagapudi@minneamrita.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Stressing the patient's pancreatic cancer by giving the anti super-enhancer MinnelideTM 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 Record Dates

• First Submitted: September 22, 2022
• First Posted: September 28, 2022
• Study Start: November 1, 2022
• Primary Completion: June 1, 2024
• Study Completion: December 1, 2024
• Last Updated: December 9, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)