Clinical Trials /

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

NCT03654833

Description:

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.

Related Conditions:
  • Malignant Mesothelioma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 0627
  • NCT ID: NCT03654833

Conditions

  • Mesothelioma, Malignant

Interventions

DrugSynonymsArms
RucaparibCO-338MiST1 Rucaparib
AbemaciclibLY2835219MiST2 Abemaciclib
pembrolizumab & bemcentinibKeytruda; BGB324MiST3 Pembrolizumab & Bemcentinib
Atezolizumab & BevacizumabMPDL3280A; AvastinMiST4 Atezolizumab & Bevacizumab

Purpose

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
      and 4, immune checkpoint, transcriptomic and gut microbiome correlative studies are planned.
    

Trial Arms

NameTypeDescriptionInterventions
MiST1 RucaparibExperimentalBRCA1/BAP1 negative mesothelioma; 600mg twice daily (BID) every 28 days.
  • Rucaparib
MiST2 AbemaciclibExperimentalp16INK4A negative mesothelioma; 200mg orally twice daily every 28 days.
  • Abemaciclib
MiST3 Pembrolizumab & BemcentinibExperimentalNo 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.
  • pembrolizumab & bemcentinib
MiST4 Atezolizumab & BevacizumabExperimentalPDL1 expression positive mesothelioma: Atezolizumab 1200 milligrams via intravenous nfusion; Bevacizumab 15 milligrams per kilogram via IV infusion both on Days 1 every 21-days.
  • Atezolizumab & Bevacizumab

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease control rate (DCR) at 12 weeks assessed by modified RECIST 1.1, in patients with relapsed mesothelioma.
Time Frame:12 weeks
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Disease control rate (DCR) at 24 weeks assessed by modified RECIST 1.1, in patients with relapsed mesothelioma.
Time Frame:24 weeks
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description:This will be assessed using CT scan evidence according to modified RECIST 1.1 criteria
Measure:Safety assessed according to CTCAE criteria.
Time Frame:12 months (up to 6 months during treatment and 6 months of follow-up)
Safety Issue:
Description: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.
Measure:Toxicity assessed according to CTCAE criteria.
Time Frame:12 months (up to 6 months during treatment and 6 months of follow-up)
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Leicester

Trial Keywords

  • Drug: multi-arm
  • Phase IIa

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