A Phase II, International Open Label Trial of Minnelide™ in Patients With Refractory Pancreatic Cancer (MinPAC)

MinPAC: A Phase II, International Open Label Trial of Minnelide™ in Patients With Refractory Pancreatic Cancer.

MinPAC aims to see if the drug Minnelide can slow down tumour growth in patients with pancreatic cancer that is not responding to treatment. Minnelide is designed to rapidly release the anti-tumour molecule triptolide in the bloodstream and has been shown to slow cancer cell growth and induce cancer cell death. Minnelide is currently being investigated in other early phase trials and has shown promising response data.

There are strict eligibility criteria for this trial. Broadly speaking, patients with pancreatic cancer that has spread to other organs and has progressed on one or more chemotherapy regimens are eligible. Participants will receive Minnelide on days 1-21 of each 28 day cycle until their cancer stops responding to treatment. After that participants will be followed up 3 monthly for the collection of disease status and survival data.

MinPAC includes biological and imaging studies. Participants will be asked to donate tumour and blood samples and will be asked to undergo additional PET Scans. The study is being carried out in 4 sites in the UK and USA.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Minnelide

Detailed Description

MinPAC is an open label, international, multicentre phase II trial that aims to evaluate the effects of Minnelide treatment in patients with refractory pancreatic cancer. Eligible patients will receive Minnelide until disease progression unless there is evidence of unacceptable toxicity or the patient requests to be withdrawn from the study treatment. Once disease progression is documented, patients will enter a follow up phase during which data will be collected on further disease and survival status. If patients are unable to attend hospital visits during the follow up period then data will be collected either via telephone or via national registries with the patient's consent. The efficacy of Minnelide will be assessed on CT/MRI scan images and tumour and/or blood samples collected at baseline, during treatment and on completion of treatment.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Honorhealth Research Institute
  • California
    • La Jolla, California, United States, 92037
      • Moores UC San Diego Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Willing and able to provide written informed consent.
2. Ability to comply with the protocol.
3. Aged ≥ 18 years.
4. Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma that has progressed on one or more chemotherapy regimens.
5. Karnofsky performance status ≥ 70%.
6. At least one lesion that can be measured accurately at baseline as ≥10mm in the longest diameter (except lymph nodes which must have a short axis ≥15mm) with CT/MRI and which is suitable for repeated measurements per RECIST v1.1
7. Adequate haematological and end-organ function, as per the local institutions reference ranges, within 72 hrs prior to day 1 of cycle 1 of treatment defined by the following:
8. Life expectancy ≥ 12 weeks.
9. Negative pregnancy test within 14 days of day 1 cycle 1 for female patients of childbearing potential.
10. Tumour sites amenable to repeated biopsies.
11. Willingness to undergo paired tumour biopsies during the trial.
12. Agreement to use adequate contraception from 2 weeks before the start of treatment with Minnelide and until 90 days after completion of treatment.

Exclusion Criteria:

1. Patients with known or suspected brain metastasis
2. Significant cardiovascular disease such as New York Heart Associate Class III/IV, cardiac failure, myocardial infarction within 6 months prior to enrolment, unstable arrhythmia, or evidence of ischemia on ECG.
3. Baseline QTc exceeding 450msec (470msec for females) and / or patients receiving class 1A or class III anti-arrhythmic agents.
4. Known HIV, Hepatitis A, B or C infection.
5. Malignancies other than pancreatic cancer ≤5 years prior to Minnelide cycle 1 day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcomes (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer or ductal carcinoma in situ treated surgically with curative intent) or localised prostate cancer treated with curative intent and absence of PSA relapse or incidental prostate cancer (Gleason score ≤3 +4 and PSA <10ng/L undergoing active surveillance and treatment naïve).
6. Severe infections ≤ 4 weeks prior to enrolment in the study as well as active, uncontrolled bacterial, viral or fungal infections requiring systemic treatment.
7. Major surgical procedure ≤ 2 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
8. Treatment with chemotherapy or other investigational agents within 28 days (or at least 5 x the half-life of the drug) prior to day 1 cycle 1 of Minnelide™ (6 weeks for nitrosoureas or Mitomycin C).
9. Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational medicinal product (IMP) within ≤ 5 x the half-life of the IMP prior to day 1 cycle 1 of Minnelide.
10. Any other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of Minnelide, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent.
11. Female patients who are pregnant or nursing.

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: Minnelide; 0.67 mg/m2 Minnelide daily as a 30min iv infusion on days 1-21 of each 28 day cycle, followed by a 7 day rest period (D 22-28).	Drug: Minnelide; Minnelide will be administered at the dose of 0.67 mg/m2 as a 30 min infusion intravenously daily on days 1-21 of each cycle followed by a 7 day rest period (days 22-28).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control rate (DCR)	DCR (CR+PR+SD) by RECIST v1.1	Enrolment to 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Time from enrolment until disease progression or death from any cause, whichever occurs first (RECIST v1.1)	Disease progression or death, assessed up to 18 months
Incidence of adverse events	Adverse events by CTCAE v4.03	Through completion of the safety visit an average of 4 months
Overall survival (OS)	Time from enrolment until death	Death, assessed up to 18 months
Response rate (RR)	Percentage of individuals on study attaining a CR + PR (RECIST v1.1)	Enrlolment to 16 weeks
Change in tumour size and volume	Change in the sum of diameters of the target lesions	Baseline to 8 weeks
Change in CA19-9 levels	Percentage of patients with >20% decrease	Through completion of the treatment period an average of 4 months
Pharmacodynamic effect of Minnelide on tumour using PET Scans	Changes in SUV	8 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers predictive of response to Minnelide	Changes in circulating tumour stem cells.	Through completion of the treatment period an average of 4 months

Collaborators and Investigators

• Sponsor: Minneamrita Therapeutics LLC
• Collaborators: Cancer Research UK; Barts & The London NHS Trust; Queen Mary University of London; Stand Up To Cancer; Lustgarten Foundation; Translational Genomics Research Institute
• Investigators: Principal Investigator: David Propper, Barts & The London NHS Trust; Principal Investigator: Erkut Borazanci, Honorhealth Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2017
• Primary Completion (Actual): July 1, 2019
• Study Completion (Actual): July 1, 2019

Study Registration Dates

• First Submitted: March 16, 2017
• First Submitted That Met QC Criteria: April 12, 2017
• First Posted (Actual): April 18, 2017

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: Refractory pancreatic cancer; Minnelide; Minnelide002; 2017-000126-36
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; 14-O-phosphonooxymethyltriptolide disodium salt
• Other Study ID Numbers: Minnelide002

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: Yes
• Studies a U.S. FDA-regulated device product: No