Mesothelioma Stratified Therapy (MiST) : A Multi-drug Phase II Trial in Malignant Mesothelioma (MiST)

March 13, 2023 updated by: University of Leicester

Mesothelioma Stratified Therapy (MiST): A Stratified Multi-arm Phase IIa Clinical Trial to Enable Accelerated Evaluation of Targeted Therapies for Relapsed Malignant Mesothelioma

MiST is a British Lung Foundation funded, University of Leicester Study, a multi-arm stratified therapy based clinical trial for patients with relapsed mesothelioma.

The goal of MiST is to enable acceleration of novel, effective personalised therapy as a basis for improving survival outcomes for patients with mesothelioma.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Stage 1 - molecular pre-screening:

The MiST Master protocol describes the identification of patients, biomarker testing and analysis. Patients with relapsed mesothelioma will be offered to consent for molecular panel testing of their diagnostic tumour block for predictive biomarkers. The results of this assessment will be used to classify patients into one of several possible molecularly defined treatment arms. Patients will therefore be offered a specific study treatment determined by their molecular profile. Patients, who exhibit positive testing in more than one biomarker, will potentially be eligible to subsequently be treated on a different treatment protocol upon disease progression or treatment failure.

Stage 2 - Treatment:

The MiST treatment protocol will be specific to the treatment allocated to the patient - based on the results of their biomarker testing in stage 1.

Specific agent(s) will be detailed separately in each of the separate treatment protocols.

Stage 3 - Molecular Profiling :

In order to understand the genomic basis of drug response in the MiST trial, archival tumour tissue from all patients enrolled will be interrogated using molecular inversion probe- based microarray analysis of the somatic copy number aberrations. Optional re-biopsy of patients who progress on treatment, followed confirmed radiological response, will be offered, to investigate genomic interrogation of tumours at the time of acquired resistance. For arms 3, 4 and 5 immune checkpoint, transcriptomic and gut microbiome correlative studies are planned.

Study Type

Interventional

Enrollment (Actual)

186

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Kingdom
      • Leicester, United Kingdom, LE1 5WW
        • University Hospitals of Leicester NHS Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

INCLUSION CRITERIA FOR PRE-SCREENING

  • Histologically confirmed MM with an available biopsy for research purposes
  • Male or female patients aged ≥18 years.
  • Expected survival of ≥12 weeks or greater
  • ECOG PS 0-1
  • CT scan chest, abdomen (and pelvis if applicable) confirming disease progression.
  • Patients must have received at least one prior line of therapy to include a platinum doublet first-line chemotherapy (within or outside of another clinical trial)
  • Willing to consent for molecular screening of archived tumour block (PIS1 & CF1)

EXCLUSION CRITERIA FOR PRE-SCREENING

  • Patients with a diagnosis of a second malignancy except prostate or cervical cancer in remission, patients with a diagnosis of basal cell carcinoma of the skin or superficial bladder cancer.
  • Uncontrolled CNS disease. Asymptomatic brain metastases are allowed if previously treated with radiotherapy >28 days prior to starting the investigational agent.
  • New York Heart Association Class II or greater congestive heart failure.
  • Patients with severe hepatic insufficiency or severe renal impairment.
  • Patients requiring long term oxygen therapy.
  • Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.

Each individual MiST drug protocol contains the eligibility criteria specific to the treatment allocated to the patient.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MiST1 Rucaparib
BRCA1/BAP1 negative mesothelioma; 600mg twice daily (BID) every 28 days.
Drug: Rucaparib
PARP inhibitor
Other Names:
  • CO-338
Experimental: MiST2 Abemaciclib
p16INK4A negative mesothelioma; 200mg orally twice daily every 28 days.
Drug: Abemaciclib
CDK4/6 inhibitor
Other Names:
  • LY2835219
Experimental: MiST3 Pembrolizumab & Bemcentinib

No specific biomarker requirement: Pembrolizumab 200mg IV infusion on Day 1 only:

Bemcentinib loading dose of 400mg on days 1-3, on day 4 on-wards 200mg daily every 21-days.
Drug: pembrolizumab & bemcentinib
PD1 checkpoint inhibitor, AXL inhibitor
Other Names:
  • Keytruda; BGB324
Experimental: MiST4 Atezolizumab & Bevacizumab
PDL1 expression positive mesothelioma: Atezolizumab 1200 milligrams via intravenous nfusion; Bevacizumab 15 milligrams per kilogram via IV infusion both on Days 1 every 21-days.
Drug: Atezolizumab & Bevacizumab
PDL1 checkpoint inhibitor, VEGF inhibitor
Other Names:
  • MPDL3280A; Avastin
Experimental: MiST 5 Dostarlimab and Niraparib
Platinum sensitive mesothelioma: Niraparib 200-300mg daily every 21 days; Dostarlimab 500mg on day 1 of each 21 day cycle for 4 cycles, then 1000mg on day 1 of each 42 day cycle.
Drug: Dostarlimab and Niraparib
IG Antibody, PARP Inhibitor
Other Names:
  • Zejula

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease control rate (DCR) at 12 weeks assessed by modified RECIST 1.1, in patients with relapsed mesothelioma.
Time Frame: 12 weeks
This will be assessed using CT scan evidence according to modified RECIST 1.1 criteria reporting. Scans will be undertaken every 6 weeks. Analysis will be timed from study entry using the baseline CT scan results until completion of treatment cycles, confirmed disease progression or death - whichever comes first.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease control rate (DCR) at 24 weeks assessed by modified RECIST 1.1, in patients with relapsed mesothelioma.
Time Frame: 24 weeks
This will be assessed using CT scan evidence according to modified RECIST 1.1 criteria reporting. Scans will be undertaken every 6 weeks. Analysis will be timed from study entry using the baseline CT scan results until completion of treatment cycles, confirmed disease progression or death - whichever comes first.
24 weeks
Objective response rate (ORR) assessed for 12 months
Time Frame: Up to 12 months (up to 6 months during treatment and 6 months of follow-up)
This will be assessed using CT scan evidence according to modified RECIST 1.1 criteria
Up to 12 months (up to 6 months during treatment and 6 months of follow-up)
Safety assessed according to CTCAE criteria.
Time Frame: 12 months (up to 6 months during treatment and 6 months of follow-up)
Adverse events will be recorded in relation to each cycle of treatment and graded according to Common Terminology Criteria for Adverse Events (CTCAE). The incidence of each adverse event (all grades and grade 3/4) will be reported as a per-patient-cycle rate and as a per-patient rate. Investigators expect patients to participate in the study for a maximum of 6 months of Treatment and 6 months of follow-up, however cannot guarantee that some patients may participate over 12 months.
12 months (up to 6 months during treatment and 6 months of follow-up)
Toxicity assessed according to CTCAE criteria.
Time Frame: 12 months (up to 6 months during treatment and 6 months of follow-up)
Adverse events will be recorded in relation to each cycle of treatment and graded according to Common Terminology Criteria for Adverse Events (CTCAE). The incidence of each adverse event (all grades and grade 3/4) will be reported as a per-patient-cycle rate and as a per-patient rate. Investigators expect patients to participate in the study for a maximum of 6 months of Treatment and 6 months of follow-up, however cannot guarantee that some patients may participate over 12 months.
12 months (up to 6 months during treatment and 6 months of follow-up)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Leicester

Collaborators

Eli Lilly and Company
GlaxoSmithKline
Merck Sharp & Dohme LLC
Roche Pharma AG
British Lung Foundation
Clovis Oncology, Inc.
University Hospitals, Leicester
The Christie NHS Foundation Trust
BerGenBio ASA

Investigators

  • Study Director: Dean Fennell, PhD, FRCP, University of Leicester

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 28, 2019

Primary Completion (Anticipated)

October 31, 2023

Study Completion (Anticipated)

October 31, 2023

Study Registration Dates

First Submitted

August 7, 2018

First Submitted That Met QC Criteria

August 30, 2018

First Posted (Actual)

August 31, 2018

Study Record Updates

Last Update Posted (Actual)

March 14, 2023

Last Update Submitted That Met QC Criteria

March 13, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0627

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

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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