Clinical trial NCT03654833: Mesothelioma Stratified Therapy (MiST) : A Multi-drug Phase II Trial in Malignant Mesothelioma
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Mesothelioma, Malignant
Keywords: Drug: multi-arm
Phase IIa
Lead sponsor: University of Leicester
Sponsor class: OTHER
Collaborators: name: British Lung Foundation
name: Clovis Oncology, Inc.
name: Eli Lilly and Company
name: Merck Sharp & Dohme LLC
name: BerGenBio ASA
name: Roche Pharma AG
name: University Hospitals, Leicester
name: The Christie NHS Foundation Trust
name: GlaxoSmithKline
First posted: 2018-08-31
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Disease control rate (DCR) at 12 weeks assessed by modified RECIST 1.1, in patients with relapsed mesothelioma.
timeFrame: 12 weeks
Secondary outcomes:
measure: Disease control rate (DCR) at 24 weeks assessed by modified RECIST 1.1, in patients with relapsed mesothelioma.
timeFrame: 24 weeks
measure: Objective response rate (ORR) assessed for 12 months
timeFrame: Up to 12 months (up to 6 months during treatment and 6 months of follow-up)
measure: Safety assessed according to CTCAE criteria.
timeFrame: 12 months (up to 6 months during treatment and 6 months of follow-up)
measure: Toxicity assessed according to CTCAE criteria.
timeFrame: 12 months (up to 6 months during treatment and 6 months of follow-up)
Other outcomes:
Locations:
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust
Study officials:
affiliation: University of Leicester
name: Dean Fennell, PhD, FRCP
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.