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

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.

Overall Status

Recruiting

Start Date

2019-01-28

Completion Date

2021-11-30

Primary Completion Date

2021-07-30

Phase

Phase 2

Study Type

Interventional

Primary Outcome

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

Secondary Outcome

Measure	Time Frame
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)

Enrollment

120

Condition

Mesothelioma, Malignant

MPDL3280A; Avastin

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.

Gender

All

Minimum Age

18 Years

Maximum Age

N/A

Healthy Volunteers

Overall Official

Last Name	Role	Affiliation
Anne Thomas, PhD, FRCP	Study Director	University of Leicester
Dean Fennell, PhD, FRCP	Principal Investigator	University of Leicester

Overall Contact

Last Name

Amy King, MSc

Phone

+44 (0)116 229

Phone Ext

7249

Email

[email protected]

Location

Facility	Status	Contact	Investigator
University Hospitals of Leicester NHS Trust Leicester LE1 5WW United Kingdom	Recruiting	Last Name: Molly Scotland, Nurse Phone: 0116 204 Phone Ext: 7872	Last Name: Dean Fennell, PhD, FRCP Role: Principal Investigator

Location Countries

Country

United Kingdom

Verification Date

2020-01-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Responsible Party

Responsible Party Type

Sponsor

Keywords

Drug: multi-arm

, Phase IIa

Has Expanded Access

Condition Browse

Mesothelioma

Number Of Arms

Intervention Browse

Mesh Term

Bevacizumab

Pembrolizumab

Atezolizumab

Rucaparib

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.

Firstreceived Results Date

N/A

Overall Contact Backup

Last Name

Amy Branson, LLB

Phone

+44 (0)116 229

Phone Ext

7309

Email

[email protected]

Acronym

MiST

Patient Data

Sharing Ipd

Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Non-Randomized

Intervention Model

Parallel Assignment

Primary Purpose

Treatment

Masking

None (Open Label)

Study First Submitted

August 7, 2018

Study First Submitted Qc

August 30, 2018

Study First Posted

August 31, 2018

Last Update Submitted

January 29, 2020

Last Update Submitted Qc

January 29, 2020

Last Update Posted

January 30, 2020

ClinicalTrials.gov processed this data on May 29, 2020

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.

Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.

Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.

ICH GCP | Clinical Trials Registry

Mesothelioma Stratified Therapy (MiST): A Stratified Multi-arm Phase IIa Clinical Trial to Enable Accelerated Evaluation of Targeted Therapies for Relapsed Malignant Mesothelioma