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

Study Overview
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Brief Summary
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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.

Detailed Description
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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Minnelide until disease progression unless there is evidence of unacceptable toxicity or the patient requests to be withdrawn from the study treatment.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.

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

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Minnelide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide written informed consent. Ability to comply with the protocol. Aged ≥ 18 years. Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma that has progressed on one or more chemotherapy regimens. Karnofsky performance status ≥ 70%. 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 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: Life expectancy ≥ 12 weeks. Negative pregnancy test within 14 days of day 1 cycle 1 for female patients of childbearing potential. Tumour sites amenable to repeated biopsies. Willingness to undergo paired tumour biopsies during the trial. 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: Patients with known or suspected brain metastasis 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. Baseline QTc exceeding 450msec (470msec for females) and / or patients receiving class 1A or class III anti-arrhythmic agents. Known HIV, Hepatitis A, B or C infection. 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). Severe infections ≤ 4 weeks prior to enrolment in the study as well as active, uncontrolled bacterial, viral or fungal infections requiring systemic treatment. 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. 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). 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. 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. Female patients who are pregnant or nursing.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single arm, open label study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Minnelide<br>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<br>* 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).<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Refractory pancreatic cancer, Minnelide, Minnelide002, 2017-000126-36