Efficacy of a Maintenance Treatment With TALAzoparib Following First Line Platinum-based Chemotherapy in Malignant MESOthelioma

NCT04462809 | Unknown Phase 2

• 1 other identifier: 69HCL19_0457
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

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).

Conditions

Advanced Malignant Pleural or Peritoneal Mesothelioma

Keywords

Talazoparib; maintenance-based treatment; PARP-inhibitor; malignant pleural mesothelioma; malignant peritoneal mesothelioma; predictive biomarkers

Outcome Measures

Primary Outcomes (1)

• Non-progression proportion

  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.

  6 month after starting talazoparib

Secondary Outcomes (5)

• Progression free survival

  Patients will be followed until the end of the study for collect date on progression and date of eventually death : .25 month for the latest enrolled patient to 49 months for the first one.)

• Progression free-survival based on RECIST 1.1 criteria

  Patients will be followed until the end of the study for collect date on progression and date of eventually death : .25 month for the latest enrolled patient to 49 months for the first one.

• Progression free-survival based on mRECIST criteria

  Patients will be followed until the end of the study for collect date on progression and date of eventually death : .25 month for the latest enrolled patient to 49 months for the first one.

• Overall Survival

  Patients will be followed until the end of the study for collect date on progression and date of eventually death : .25 month for the latest enrolled patient to 49 months for the first one.

• Safety, treatment-related adverse events

  6 weeks after the last experimental treatment for the latest enrolled patient

Study Arms (3)

Cohort A, Malignant pleural mesothelioma

EXPERIMENTAL

Malignant pleural mesothelioma

Drug: Talazoparib

Cohort B1:Malignant peritoneal mesothelioma non-resected

EXPERIMENTAL

Malignant peritoneal mesothelioma with non-resected or incompletely resected disease

Drug: Talazoparib

Cohort B2:Malignant peritoneal mesothelioma (resected)

EXPERIMENTAL

Malignant peritoneal mesothelioma with completely resected disease.

Drug: Talazoparib

Interventions

Talazoparib DRUG

Talazoparib 1 mg a day (PO) (or 0.75 mg a day) for 2 years, started between 6 to 8 weeks after the end of chemotherapy discontinuation. Talazoparib will be given for up to 2 years, or less length of time in the case of disease progression,. unacceptable toxicity despite adequate management,patient decides to withdraw from the study, or general or specific changes in the patient's condition render the patient unacceptable for further treatment.

Cohort A, Malignant pleural mesothelioma; Cohort B1:Malignant peritoneal mesothelioma non-resected; Cohort B2:Malignant peritoneal mesothelioma (resected)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 treatment with pressurized intraperitoneal aerosol chemotherapy sessions (PIPAC) are not allowed.
• Measurable or non-measurable (but radiologically evaluable) disease as per modified RECIST version 1.1 on computed tomography (CT) scan (within 28 days of talazoparib initiation)
• Availability at the study site of a representative 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 as defined below:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

talazoparib

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Benoit YOU

CONTACT

4 78 864 318; benoit.you@chu-lyon.fr

Laurent VILLENEUVE

CONTACT

4 78 864 536; laurent.villeneuve@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2020
• First Posted: July 8, 2020
• Study Start: September 1, 2020
• Primary Completion: March 1, 2021
• Study Completion: October 1, 2024
• Last Updated: July 9, 2020

Record last verified: 2020-07