Mesothelioma, MalignantPhase 2MiSTNCT03654833
Mesothelioma Stratified Therapy (MiST) : A Multi-drug Phase II Trial in Malignant Mesothelioma
A Phase 2 study testing Rucaparib, Abemaciclib and pembrolizumab & bemcentinib in people with Mesothelioma, Malignant, run by University of Leicester at 1 site in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mesothelioma, Malignant
- What is being tested?
- Rucaparib, Abemaciclib and pembrolizumab & bemcentinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 186 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 28 Jan 2019to 15 Mar 2024
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University Hospitals of Leicester NHS Trust
Leicester, LE1 5WW
About this study
Official title: 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.
Read the 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.
- Conditions
- Mesothelioma, Malignant
- Being tested
- Rucaparib, Abemaciclib, pembrolizumab & bemcentinib, Atezolizumab & Bevacizumab, Dostarlimab and Niraparib
- Keywords
- Drug: multi-arm, Phase IIa
- Medical subject headings
- Mesothelioma, Malignant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RucaparibDrug
Also called CO-338
PARP inhibitor
AbemaciclibDrug
Also called LY2835219
CDK4/6 inhibitor
pembrolizumab & bemcentinibDrug
Also called Keytruda; BGB324
PD1 checkpoint inhibitor, AXL inhibitor
Atezolizumab & BevacizumabDrug
Also called MPDL3280A; Avastin
PDL1 checkpoint inhibitor, VEGF inhibitor
Dostarlimab and NiraparibDrug
Also called Zejula
IG Antibody, PARP Inhibitor
| Study group | Role | What they receive |
|---|---|---|
| MiST1 Rucaparib | Experimental | BRCA1/BAP1 negative mesothelioma; 600mg twice daily (BID) every 28 days. Receives: Drug: Rucaparib |
| MiST2 Abemaciclib | Experimental | p16INK4A negative mesothelioma; 200mg orally twice daily every 28 days. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Dostarlimab and Niraparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Complete response (CR): disappearance of all target and non-target lesions with no evidence of tumour elsewhere Partial response (PR): reduction of at least 30% in the sum of all measurements with no evidence of significant disease progression in non-target lesions or new lesions Progressive disease (PD): 1: increase of at least 20% in the sum of all measurements compared with the previous best response, 2: appearance of one or more significant (overall 20% increase in tumour diameters) new lesions, 3: significant increase in target lesions Stable disease (SD): neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD
Measured: 12 weeks
Secondary outcomes (2)
Disease Control Rate (DCR) at 24 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.
Complete response (CR): disappearance of all target and non-target lesions with no evidence of tumour elsewhere Partial response (PR): reduction of at least 30% in the sum of all measurements with no evidence of significant disease progression in non-target lesions or new lesions Progressive disease (PD): 1: increase of at least 20% in the sum of all measurements compared with the previous best response, 2: appearance of one or more significant (overall 20% increase in tumour diameters) new lesions, 3: significant increase in target lesions Stable disease (SD): neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD
Measured: 24 weeks
Objective Response Rate (ORR) at 24 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.
Complete response (CR): disappearance of all target and non-target lesions with no evidence of tumour elsewhere Partial response (PR): reduction of at least 30% in the sum of all measurements with no evidence of significant disease progression in non-target lesions or new lesions Progressive disease (PD): 1: increase of at least 20% in the sum of all measurements compared with the previous best response, 2: appearance of one or more significant (overall 20% increase in tumour diameters) new lesions, 3: significant increase in target lesions Stable disease (SD): neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2018
- Study start28 Jan 2019
- Primary completion21 Feb 2023
- Study completion15 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Mesothelioma, MalignantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 186 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Leicester
- Sponsor type
- University, hospital or other
- Collaborators
- British Lung Foundation, Clovis Oncology, Inc., Eli Lilly and Company, Merck Sharp & Dohme LLC, BerGenBio ASA, Roche Pharma AG, University Hospitals, Leicester, The Christie NHS Foundation Trust, GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Dean Fennell, PhD, FRCP, Study director, University of Leicester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03654833
- Sponsor's protocol ID
- 0627
- Acronym
- MiST
- Status last verified
- Nov 2022
- First submitted
- 7 Aug 2018
- Last updated
- 17 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35157829Fennell 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.
PubMed 33515503