Sertraline added to chemotherapy for advanced epithelioid pleural mesothelioma

Who can take part

• Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained, and documented according to the local regulatory requirements
• Age at the time of signing the informed consent at least 18 years
• Diagnosis of treatment naïve epithelioid MPM, histologically confirmed, preferably by video-assisted thoracoscopic surgery (VATS)
• Measurable disease, defined as at least 1 lesion measured in two positions at three separate levels on transverse cuts of CT scan that is suitable for repeated assessment using modified Response Evaluation Criteria in Solid Tumours [m-RECIST 1.1] for MPM is preferred; however, inclusion of specific cases without measurable disease could be discussed with the PI of the Promoter site and the Sponsor
• Surgical unresectable disease [stage III-IV) according to ninth TNM edition]
• Archival tumor tissue sample or newly obtained [core, incisional or excisional] biopsy of a tumor lesion not previously irradiated available. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies (less than 3 months from enrollment) are preferred to archived tissue. Archival tissue must be from the previous 12 months, or discussed with Principal Investigators
• ECOG) PS of 0 to 1
• Have adequate organ function as defined per protocol (see table 4)
• Estimated life expectancy of at least 3 months irrespective of the diagnosis of unresectable MPM

Who cannot take part

• Has had an allogenic tissue/solid organ transplant
• Concomitant use of pimozide or of monoamine oxidase inhibitors (MAOIs) or less than 14 days from last dose of MAOIs
• Has received prior radiotherapy within 2 weeks of start of study intervention or radiation- related toxicities requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention
• Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or adequately treated carcinoma in-situ without evidence of disease are not excluded. Participants with low-risk early-stage prostate cancer (T1-T2a, Gleason score ≤6, and PSA <10 ng/mL) either treated with definitive intent or untreated in active surveillance with stable disease are not excluded
• Has not adequately recovered from major surgery or has ongoing surgical complications
• Patients with a history of epileptic seizures within the last 5 years or a history of status epilepticus
• Known inherited or acquired major bleeding disorder or coagulopathy (including but not limited to hemophilia, von Willebrand disease)
• Has major psychiatric disorder not controlled or requiring chronic medical treatment
• Known hypersensitivity reaction to one of the compounds or substances used in this protocol
• Uncontrolled significant active infections (≥ grade 3 according to CTCAE version 5), including active hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency Virus (HIV). Note: Testing for Hepatitis B or C or HIV is not required unless mandated by local health authority
• Has uncontrolled, potentially reversible cardiac conditions, as Investigator’s judgment (eg. Unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation > 500 millisecond) or participants with congenital long QT syndrome
• Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
• Primitive peritoneal, pericardial and tunica vaginalis testis mesotheliomas
• Angle Closure Glaucoma with untreated anatomically narrow angles
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment