Advanced Malignant Pleural or Peritoneal Mesothelioma Clinical Trial
Official title:
A Three-Cohort Phase II Trial to Assess the Efficacy of a Maintenance Treatment With TALAzoparib Following First Line Platinum-based Chemotherapy in Pleural or Malignant Peritoneal MESOthelioma Patients
Malignant mesothelioma is an invasive neoplasm that arises from mesothelium that lines
several organs. Common primary sites of origin of mesotheliomas are the pleura (malignant
pleural mesothelioma: 85%) and peritoneum (malignant peritoneal mesothelioma 15%), and rarely
the pericardium and tunica vaginalis.
The standard of care recommended for malignant pleural mesotheliomas (MPM) is palliative
chemotherapy based on a doublet of platinum salt and an anti-folate. The median survival of
patients with pleural MPM is around 8 months with best supportive care only, 12 to 19 months
when systemic chemotherapy is used with or without anti-angiogenic agents or targeted
therapy. There is an unmet need for innovative approaches in pleural mesotheliomas.
Malignant peritoneal mesothelioma is an aggressive neoplasm that arises from the lining
mesothelial cells of the peritoneum and spreads extensively within the confines of the
abdominal cavity. Cytoreductive surgery (CRS) followed by hyperthermic intraoperative
peritoneal perfusion with chemotherapy (HIPEC) is the standard curative approach when it is
possible, with respect to peritoneal carcinomatosis extend. When the cytoreductive surgery is
impossible, the common strategy is to prescribe systemic chemotherapy, with the objective of
downsizing tumor lesions for potential subsequent CRS. The standard strategy based on
cisplatin - pemetrexed combination regimen has been extrapolated from pleural mesothelioma
management principles.
Genomic landscape of mesotheliomas is now well described. Pleural and peritoneal malignant
mesotheliomas harbor closed genomic instability.
Strategies based on maintenance-based treatments with Poly (ADP-ribose) polymerase (PARP)
inhibitors, especially olaparib, niraparib and talazoparib, have been shown effective in
ovarian cancer patients, thereby leading to their approvals. The benefit has been mainly
observed in patients with homologous recombination deficiencies (HRD), but also in all-comers
patients in a lesser extent. It is thought that HRD induces addiction of cancer cells to
PARP, thereby leading to cell death in the presence of PARP inhibitors.
As a consequence, given the prevalence of HRD, through BAP-1 mainly, in mesotheliomas,
maintenance treatment with PARP-inhibitor in malignant mesothelioma patients without any
progressive disease after 4 to 6 cycles of platinum-based chemotherapy may be associated with
increased progression free survival, as it was shown in ovarian cancer patients.
TALAMESO aims to evaluate the efficacy of talazoparib maintenance treatment given for maximum
2 years following 4 to 6 cycles of platinum-based first line chemotherapy in terms of
proportion of patients progression free 6 months after starting the maintenance, and
progression-free survival, in patients with advanced malignant pleural (cohort A) or
peritoneal (cohorts B1 and B2) mesotheliomas.
Cohorts B1 and B2 are meant to confirm that talazoparib can increase progression free
survival in both patient populations with non-resected or incompletely resected disease
(cohort B1) or with completely resected disease (cohort B2).
TALAMESO is an open-label phase II trial with 3 independent cohorts (Fleming's single-stage)
including patients with advanced malignant pleural (cohort A) or peritoneal (cohort B1 and
B2) mesotheliomas without any sign of disease progression after 4 to 6 cycles of
platinum-based chemotherapy (including minimum 1 cycle of pemetrexed).
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