This study involves adults subjects with advanced malignant pleural (cohort A) or peritoneal (cohorts B1 and B2) mesothelioma. The cohorts B1 will be patient populations with non-resected or incompletely resected disease and cohort B2, with completely resected disease. MedDRA version: 21.0 Level: LLT Classification code 10035605 Term: Pleural mesothelioma malignant advanced System Organ Class: 100000004864 MedDRA version: 21.0 Level: LLT Classification code 10034669 Term: Peritoneal mesothelio
Conditions
Interventions
Trade Name: TALZENNA
Pharmaceutical Form: Capsule
Sponsors
Hospices Civils de Lyon
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients older than 18 years old - Patients with Eastern Cooperative Oncology Group (ECOG) performance status = 2 - Histologically - or cytologically- confirmed malignant mesotheliomas: epithelioid, sarcomatoid, biphasic : Developed from pleura (cohort A) or from peritoneum (cohorts B1 and B2); Previously treated with first-line platinum based-chemotherapy (including minimum one cycle of pemetrexed) for 4 to 6 cycles, with no sign of disease progression during chemotherapy. - No previous treatment with bevacizumab and PARP inhibitor - Minimum 6 weeks and maximum 8 weeks interval between last chemotherapy cycle and talazoparib start : For pleural mesotheliomas (cohort A), primary or interval debulking surgery with or without hyperthermic intrapleural or intrathoracic chemotherapy (HITHOC) will be authorized, in the case of non-complete cytoreductive surgery only; For peritoneal mesotheliomas : * In cohort B1, primary or interval debulking surgery ± hyperthermic intraperitoneal chemotherapy (HIPEC) will be authorized in the case of non-complete cytoreductive surgery (CC2 or CC3) only. This cohort will also include patients with non-operated diseases * In cohort B2, complete macroscopic (CC0 or CC1) primary or interval debulking surgery ± HIPEC will be required. Intraperitoneal treatments with pressurized intraperitoneal aerosol chemotherapy sessions (PIPAC) are not allowed. - Measurable or non-measurable (but radiologically evaluable) disease - Availability at the study site of a representative Formalin-Fixed Paraffin-Embedded (FFPE) tumor sample in a block or at least 30 unstained slides from biopsy or surgery specimen, aged less than 6 months. - Patients with adequate bone marrow function measured within 28 days prior to administration of study treatment - Patients with adequate renal function - Patients with adequate hepatic function - Patients must have a life expectancy = 16 weeks. - Confirmation of non-childbearing status (pregnancy test) for women of childbearing potential. - A highly effective method of contraception is required for female patients during treatment of talazoparib, and for at least 7 months after completing therapy. Advise male patients with female partners of reproductive potential and pregnant partners to use a condom, during treatment with talazoparib and for at least 4 months after the final dose. - Patients who gave its written informed consent to participate to the study. - Patients affiliated to a social insurance regime. - Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Uncontrolled intercurrent illness, including but not limited to, such as congestive heart failure; respiratory distress; liver failure; allergy, or psychiatric illness/social situations that would limit compliance with study requirement according to the investigator, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent. - Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for = 5 years. - All subjects with brain metastases or meningeal involvement. - Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 6 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment with study drug. - Persistent toxicities (CTCAE = grade 2) with the exception of alopecia and sensory neuropathy, caused by previous cancer therapy. - Treatment with other investigational agents. - Bowel occlusive syndrome, inflammatory bowel disease, immune colitis, or other gastro-intestinal disorder that does not allow oral medication such as malabsorption. - Known severe hypersensitivity reactions to PARP inhibitors. - Known HIV or AIDS related illness. - Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV antibody tested positive). - Treatment with oral anticoagulant anti-vitamin K such Coumadin®. - Prior organ transplantation, including allogeneic stem cell transplantation (excluding autologous bone marrow transplant). - Patients under guardianship. - Women who are breastfeeding (during treatment with talazoparib and for at least 1 month after the final dose). - Participation in other interventional clinical research that may interfere with the experimental drugs efficacy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy, assessed by the proportion of patients who are free of progression 6 months after starting talazoparib maintenance treatment, that will follow 4 to 6 cycles of platinum-based first line chemotherapy, in patients with advanced malignant pleural (cohort A) or peritoneal mesothelioma (cohorts B1 and B2).;Secondary Objective: To assess other efficacy parameters, and survivals To assess the safety ;Primary end point(s): Non-progression proportion 6 months after starting talazoparib in TALAMESO trial. The non-progression proportion is defined as the proportion of patients free of progression 6 months after talazoparib start. Disease progression will be based on (i) tumor assessment made by the investigators according to the RECIST 1.1 criteria and/or, (ii) non-equivocal clinical symptom of disease progression according to the investigator; (iii) death related to disease progression;Timepoint(s) of evaluation of this end point: 6 months after starting talazoparib in TALAMESO trial. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Related to progression free-survival based on RECIST 1.1 criteria The Progression-Free Survival (PFS) is defined as the time from inclusion to first documented disease progression or death related to disease progression, whichever occurs first or, end of follow-up. If the treatment is stopped for another cause, the event will be censored to the date of the end of the treatment. Disease progression will be based on tumor assessment made by the investigators according to the RECIST 1.1 and/or, non-equivocal clinical symptom of disease progression according to the investigator, and/or death related to disease progression. Related to progression free-survival based on mRECIST criteria The Progression-Free Survival (PFS) is defined as the time from inclusion to first documented disease progression or death related to disease progression, whichever occurs first or, end of follow-up. If the treatment is stopped for another cause, the event will be censored to the date of the end of the treatment. Disease progression will be based on tumor assessment made by the investigators according to the mRECIST and/or, non-equivocal clinical symptom of disease progression according to the investigator, and/or death related to disease progression. Related to overall survival The Overall Survival (OS) will be estimated from the date of inclusion to the date of death or to the end of follow-up. The follow-up will end at the date of death, the date of last news or the data cutoff, whichever will come first. Data on patients lost to follow-up or without death at the data cutoff will be censored. Related to safety Safety is defined as the nature, number and grade of adverse events observed throughout the study and assessed using NCI-CTCAE v.5.0 criteria.;Timepoint(s) of evaluation of this end point: The Progression-Free Survival (PFS) is defined as the time from inclusion to first documented disease progression or death related to disease progression, whichever oc | — |
Countries
France
Contacts
Public ContactIUNG Annie
Hospices Civils de Lyon
Outcome results
None listed