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

NCT03117920 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: Minnelide002
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 3

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.

Conditions

Pancreatic Cancer

Keywords

Refractory pancreatic cancer; Minnelide; Minnelide002; 2017-000126-36

Outcome Measures

Primary Outcomes (1)

• Disease Control rate (DCR)

  DCR (CR+PR+SD) by RECIST v1.1

  Enrolment to 16 weeks

Secondary Outcomes (7)

• Progression Free Survival (PFS)

  Disease progression or death, assessed up to 18 months

• Incidence of adverse events

  Through completion of the safety visit an average of 4 months

• Overall survival (OS)

  Death, assessed up to 18 months

• Response rate (RR)

  Enrlolment to 16 weeks

• Change in tumour size and volume

  Baseline to 8 weeks

Other Outcomes (1)

• Biomarkers predictive of response to Minnelide

  Through completion of the treatment period an average of 4 months

Study Arms (1)

Minnelide

EXPERIMENTAL

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

Interventions

Minnelide DRUG

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).

Minnelide

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Minneamrita Therapeutics LLC: lead
• Barts & The London NHS Trust: collaborator
• Translational Genomics Research Institute: collaborator
• Stand Up To Cancer: collaborator
• Cancer Research UK: collaborator
• Lustgarten Foundation: collaborator
• Queen Mary University of London: collaborator

Study Sites (3)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

Moores UC San Diego Cancer Center

La Jolla, California, 92037, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

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

• David Propper

  Barts & The London NHS Trust

  PRINCIPAL INVESTIGATOR

• Erkut Borazanci

  HonorHealth Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single arm, open label study.

Study Record Dates

• First Submitted: March 16, 2017
• First Posted: April 18, 2017
• Study Start: April 10, 2017
• Primary Completion: July 1, 2019
• Study Completion: July 1, 2019
• Last Updated: October 18, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)