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

NCT03654833 | Unknown Phase 2 DMC

• 1 other identifier: 0627
• Study Type: interventional
• Target: 186
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mesothelioma, Malignant

Keywords

Drug: multi-arm; Phase IIa

Outcome Measures

Primary Outcomes (1)

• Disease control rate (DCR) at 12 weeks assessed by modified RECIST 1.1, in patients with relapsed mesothelioma.

  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 Outcomes (4)

• Disease control rate (DCR) at 24 weeks assessed by modified RECIST 1.1, in patients with relapsed mesothelioma.

  24 weeks

• Objective response rate (ORR) assessed for 12 months

  Up to 12 months (up to 6 months during treatment and 6 months of follow-up)

• Safety assessed according to CTCAE criteria.

  12 months (up to 6 months during treatment and 6 months of follow-up)

• Toxicity assessed according to CTCAE criteria.

  12 months (up to 6 months during treatment and 6 months of follow-up)

Study Arms (5)

MiST1 Rucaparib

EXPERIMENTAL

BRCA1/BAP1 negative mesothelioma; 600mg twice daily (BID) every 28 days.

Drug: Rucaparib

MiST2 Abemaciclib

EXPERIMENTAL

p16INK4A negative mesothelioma; 200mg orally twice daily every 28 days.

Drug: Abemaciclib

MiST3 Pembrolizumab & Bemcentinib

EXPERIMENTAL

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

MiST4 Atezolizumab & Bevacizumab

EXPERIMENTAL

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

MiST 5 Dostarlimab and Niraparib

EXPERIMENTAL

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

Interventions

Rucaparib DRUG

PARP inhibitor

Also known as: CO-338

MiST1 Rucaparib

Abemaciclib DRUG

CDK4/6 inhibitor

Also known as: LY2835219

MiST2 Abemaciclib

pembrolizumab & bemcentinib DRUG

PD1 checkpoint inhibitor, AXL inhibitor

Also known as: Keytruda; BGB324

MiST3 Pembrolizumab & Bemcentinib

Atezolizumab & Bevacizumab DRUG

PDL1 checkpoint inhibitor, VEGF inhibitor

Also known as: MPDL3280A; Avastin

MiST4 Atezolizumab & Bevacizumab

Dostarlimab and Niraparib DRUG

IG Antibody, PARP Inhibitor

Also known as: Zejula

MiST 5 Dostarlimab and Niraparib

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

University Hospitals of Leicester NHS Trust

Leicester, LE1 5WW, United Kingdom

Location

Related Publications (2)

• Fennell DA, King A, Mohammed S, Greystoke A, Anthony S, Poile C, Nusrat N, Scotland M, Bhundia V, Branson A, Brookes C, Darlison L, Dawson AG, Gaba A, Hutka M, Morgan B, Bajaj A, Richards C, Wells-Jordan P, Thomas A; MiST2 study group. Abemaciclib in patients with p16ink4A-deficient mesothelioma (MiST2): a single-arm, open-label, phase 2 trial. Lancet Oncol. 2022 Mar;23(3):374-381. doi: 10.1016/S1470-2045(22)00062-6. Epub 2022 Feb 11.

  PMID: 35157829 DERIVED

• Fennell DA, King A, Mohammed S, Branson A, Brookes C, Darlison L, Dawson AG, Gaba A, Hutka M, Morgan B, Nicholson A, Richards C, Wells-Jordan P, Murphy GJ, Thomas A; MiST1 study group. Rucaparib in patients with BAP1-deficient or BRCA1-deficient mesothelioma (MiST1): an open-label, single-arm, phase 2a clinical trial. Lancet Respir Med. 2021 Jun;9(6):593-600. doi: 10.1016/S2213-2600(20)30390-8. Epub 2021 Jan 27.

  PMID: 33515503 DERIVED

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

rucaparib; abemaciclib; pembrolizumab; bemcentinib; atezolizumab; Bevacizumab; dostarlimab; niraparib

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Dean Fennell, PhD, FRCP

  University of Leicester

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2018
• First Posted: August 31, 2018
• Study Start: January 28, 2019
• Primary Completion: October 31, 2023
• Study Completion: October 31, 2023
• Last Updated: March 14, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)