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

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ClinicalTrials.gov Identifier: NCT03654833
Recruitment Status : Not yet recruiting
First Posted : August 31, 2018
Last Update Posted : August 31, 2018
Sponsor:
Collaborators:
British Lung Foundation
Clovis Oncology, Inc.
Eli Lilly and Company
Merck Sharp & Dohme Corp.
BerGenBio ASA
Roche Pharma AG
University Hospitals, Leicester
The Christie NHS Foundation Trust
Information provided by (Responsible Party):
University of Leicester

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.


Condition or disease Intervention/treatment Phase
Mesothelioma, Malignant Drug: Rucaparib Drug: Abemaciclib Drug: pembrolizumab & bemcentinib Drug: Atezolizumab & Bevacizumab Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : October 1, 2018
Estimated Primary Completion Date : July 30, 2021
Estimated Study Completion Date : November 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Mesothelioma

Arm Intervention/treatment
Experimental: MiST1 Rucaparib
BRCA1/BAP1 negative mesothelioma; 600mg twice daily (BID) every 28 days.
Drug: Rucaparib
PARP inhibitor
Other Name: CO-338

Experimental: MiST2 Abemaciclib
p16INK4A negative mesothelioma; 200mg orally twice daily every 28 days.
Drug: Abemaciclib
CDK4/6 inhibitor
Other Name: 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 Name: 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 Name: MPDL3280A; Avastin




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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

  3. 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.

  4. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03654833


Contacts
Contact: Dean Fennell, PhD, FRCP +44 (0)116 252 ext 3170 df132@le.ac.uk
Contact: Amy King/Branson, MSc +44 (0)116 229 ext 7612 MesotheliomaResearch@uhl-tr.nhs.uk

Sponsors and Collaborators
University of Leicester
British Lung Foundation
Clovis Oncology, Inc.
Eli Lilly and Company
Merck Sharp & Dohme Corp.
BerGenBio ASA
Roche Pharma AG
University Hospitals, Leicester
The Christie NHS Foundation Trust
Investigators
Study Director: Dean Fennell, PhD, FRCP University of Leicester

Responsible Party: University of Leicester
ClinicalTrials.gov Identifier: NCT03654833     History of Changes
Other Study ID Numbers: 0627
First Posted: August 31, 2018    Key Record Dates
Last Update Posted: August 31, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Leicester:
Drug: multi-arm
Phase IIa

Additional relevant MeSH terms:
Mesothelioma
Lung Neoplasms
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Bevacizumab
Pembrolizumab
Atezolizumab
Rucaparib
Antibodies, Monoclonal
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Immunologic Factors
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action