Malignant Mesothelioma (MM) - pleural and peritoneal
Conditions
Interventions
Product Name: rucaparib
Product Code: CO-338
Pharmaceutical Form: Tablet
INN or Proposed INN: CO-338
CAS Number: 1859053-21-6
Sponsors
University of Leicester
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Stage 1: Registration Inclusion Criteria: •Histologically confirmed MM an available biopsy for research •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) Stage 2: Treatment Based on the result of Stage 1 (registration), patients will be enrolled according to the MiST arm eligibility criteria which will be protocol specific. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Stage 1: Registration Exclusion Criteria: •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 study, or may influence the result of the study, or the participant’s ability to participate in the study. Stage 2: Treatment Please refer to the exclusion criteria of the specific treatment protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: The timepoint for evaluation of the primary endpoint is 12 weeks. ; Main Objective: The goal of MiST is to establish an umbrella clinical trials platform to support the accelerated development of effective therapy for mesothelioma. MiST 1 will evaluate the oral poly-ADP ribose polymerase (PARP) inhibitor rucaparib in patients with a specific molecular biomarker profile (loss of expression of BAP1 and/or BRCA1) MiST2 will evaluate the oral small molecule inhibitor of CDK4 and CDK6 abemaciclib in patients with a specific molecular biomarker profile (loss of expression of p16INK4A). MiST3 will evaluate the intravenously administered drug (pembrolizumab) in combination with the oral therapy (bemcentinib) in patients with no specific biomarker. MiST4 will evaluate the intravenously administered drug combination atezolizumab and bevacizumab in patients with a specific molecular biomarker profile (positive for PDL1 expression). The primary research objective is to evaluate the disease control rate at 12 weeks in patients with MM as determined by CT scanning. ; Secondary Objective: To establish the: 1. safety, toxicity, disease control rate and objective response rate at 24 weeks of therapy in patients with relapsed mesothelioma. 2. To collect baseline diagnostic archival tissue and blood samples (and optional re-biopsies and blood samples at progression of disease), to support the identification of predictive biomarkers of sensitivity and/or resistance. Somatic genomic analysis will be used to explore the landscape of mutations and their association with clinical outcome. ; Primary end point(s): To establish the 12 week disease control rate (the proportion of patients exhibiting a combination of either tumour response or stability) of pati | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are 1. Disease progression at 24 weeks 2. objective response rate measured by modified RECIST 3. safety and tolerability 4. baseline archival tissue and optional research blood samples will be collected to support translational biomarker correlative research (with optional rebiopsy and blood sampling upon disease progression) ;Timepoint(s) of evaluation of this end point: The only timepoint for evaluation of secondary endpoints is the 24 week timepoint for assessment of disease control rate. | — |
Countries
United Kingdom
Contacts
Public ContactAmy King
University of Leicester
Outcome results
None listed