Clinical trial NCT03117920: A Phase II, International Open Label Trial of Minnelide™ in Patients With Refractory Pancreatic Cancer
Official title: MinPAC: A Phase II, International Open Label Trial of Minnelide™ in Patients With Refractory Pancreatic Cancer.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: Refractory pancreatic cancer
Minnelide
Minnelide002
2017-000126-36
Lead sponsor: Minneamrita Therapeutics LLC
Sponsor class: INDUSTRY
Collaborators: name: Barts & The London NHS Trust
name: Translational Genomics Research Institute
name: Stand Up To Cancer
name: Cancer Research UK
name: Lustgarten Foundation
name: Queen Mary University of London
First posted: 2017-04-18
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single arm, open label study.
Primary purpose: TREATMENT

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Minnelide until disease progression unless there is evidence of unacceptable toxicity or the patient requests to be withdrawn from the study treatment.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

Eligibility criteria: 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.

Primary outcomes:
measure: Disease Control rate (DCR)
timeFrame: Enrolment to 16 weeks
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Disease progression or death, assessed up to 18 months
measure: Incidence of adverse events
timeFrame: Through completion of the safety visit an average of 4 months
measure: Overall survival (OS)
timeFrame: Death, assessed up to 18 months
measure: Response rate (RR)
timeFrame: Enrlolment to 16 weeks
measure: Change in tumour size and volume
timeFrame: Baseline to 8 weeks
measure: Change in CA19-9 levels
timeFrame: Through completion of the treatment period an average of 4 months
measure: Pharmacodynamic effect of Minnelide on tumour using PET Scans
timeFrame: 8 weeks
Other outcomes:
measure: Biomarkers predictive of response to Minnelide
timeFrame: Through completion of the treatment period an average of 4 months
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute
state: Arizona
city: La Jolla
country: United States
facility: Moores UC San Diego Cancer Center
state: California
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Barts & The London NHS Trust
name: David Propper
role: PRINCIPAL_INVESTIGATOR
affiliation: HonorHealth Research Institute
name: Erkut Borazanci
role: PRINCIPAL_INVESTIGATOR
References: