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Mesothelioma, Malignant

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Neoplasms, Mesothelial

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Pleural Neoplasms

Lung Diseases

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Malignant Mesothelioma

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Enzyme Inhibitors

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Patients receive erlotinib hydrochloride PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

erlotinib hydrochloride

Hedy Kindler

The purpose of this study is to test the drug erlotinib (erlotinib hydrochloride) in people with malignant peritoneal mesothelioma who have a specific genetic mutation in their cancer. Erlotinib has been approved by the United States Food and Drug Administration (FDA) for other cancers, but erlotinib has not been approved for malignant peritoneal mesothelioma. This research is being done because there is no current standard treatment for malignant peritoneal mesothelioma and the study doctors want to see how erlotinib affects malignant peritoneal mesothelioma.

PRIMARY OBJECTIVES:

I. To determine the objective response rate (complete response \[CR\] + partial response \[PR\]) of erlotinib in malignant peritoneal mesothelioma (MPeM) patients who have epidermal growth factor receptor (EGFR) mutations.

SECONDARY OBJECTIVES:

I. To determine the percentage of patients with MPeM who have EGFR mutations. II. To characterize asbestos exposure history and other clinical parameters of patients with MPeM who do or do not have EGFR mutations.

III. To determine the disease control rate (CR + PR + stable disease \[SD\]) of MPeM patients who have EGFR mutations and are treated with erlotinib.

IV. To determine the progression-free survival (PFS) of MPeM patients who have EGFR mutations and are treated with erlotinib.

V. To determine the median overall survival (OS) of MPeM patients who have EGFR mutations and are treated with erlotinib.

VI. To evaluate toxicity in MPeM patients who have EGFR mutations and are treated with erlotinib.

TERTIARY OBJECTIVES:

I. To characterize the specific EGFR mutations observed in MPeM patients. II. To correlate tumor markers (cancer antigen \[CA\] 125 and soluble mesothelin-related peptide \[SMRP\]) with response rate, PFS, and OS in MPeM patients treated with erlotinib.

III. To correlate immunohistochemical staining of EGFR, phosphorylated (p)-EGFR, MET (Metastasis), E-cadherin, vimentin, and CBL (Casitas B-lineage Lymphoma)with EGFR mutational status and, if present, particular EGFR mutation noted.

IV. To correlate immunohistochemical staining of EGFR, p-EGFR, MET, E-cadherin, vimentin, and CBL with response rate, PFS, and OS in MPeM patients treated with erlotinib.

OUTLINE:

Patients receive erlotinib hydrochloride orally (PO) once daily (QD). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Erlotinib Hydrochloride in Treating Patients With Malignant Peritoneal Mesothelioma

Phase II Study of Erlotinib for Patients With Malignant Peritoneal Mesothelioma (MPeM) Exhibiting EGFR Mutations

Objective Response Rate is calculated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Progression free survival (PFS) defined as time from study enrollment until disease progression or death.

Overall survival measured as the time from study enrollment until death.

Toxicity is calculated in terms of adverse events per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria version 4.0

Disease Control Rate - SD + PR + CR is calculated as the percentage of patients with either complete response (CR: disappearance of all target lesions), or with partial response (PR: at least 30% decrease in the sum of longest diameter of target lesions, taking as reference the baseline sum longest diameter of target lesions), or stable disease (SD: neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease of an increase of at least 20% in the sum of the longest diameter of the target lesions taking as reference the smallest sum of longest diameter recorded since the treatment started or the appearance of one or more new lesions).

EGFR Mutations Percentage is calculated as the percentage of patients who have activating EGFR mutations among all screened patients.

National Cancer Institute (NCI)

University of Chicago

Treatment (Enzyme Inhibitor Therapy)

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

The study was terminated early after the enrollment of two participants and the data were not collected.

Objective Response Rate

Patients receive erlotinib hydrochloride PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

erlotinib hydrochloride: Given PO

laboratory biomarker analysis: Correlative studies

Toxicity

Disease Control Rate - SD + PR + CR

EGFR Mutations Percentage

Overall Study

Talazoparib

Poly(ADP-ribose) Polymerase Inhibitors

Malignant peritoneal mesothelioma with non-resected or incompletely resected disease

Malignant peritoneal mesothelioma with completely resected disease.

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.

Benoit YOU

Laurent VILLENEUVE

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).

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

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

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.

The Progression-Free Survival (PFS) is defined as the time from inclusion to (1) first documented disease progression or death related to disease progression, whichever occurs first or, (2) end of follow-up.

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. Disease progression will be based on tumor assessment made by the investigators according to the RECIST 1.1 criteria and/or, non-equivocal clinical symptom of disease progression according to the investigator, and/or death related to disease progression.

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. Disease progression will be based on tumor assessment made by the investigators according to the mRECIST criteria and/or, non-equivocal clinical symptom of disease progression according to the investigator, and/or death related to disease progression.

The Overall Survival (OS) will be estimated from the date of inclusion to the date of death or to the end of follow-up.

treatment-related adverse events are defined as the nature, number and grade of adverse events observed throughout the study and assessed using NCI-CTCAE v.5.0 criteria.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Erlotinib Hydrochloride in Treating Patients With Malignant Peritoneal Mesothelioma	NCT01592383	Malignant Perit...	erlotinib hydro...	18 Years -	University of Chicago
Erlotinib Hydrochloride in Treating Patients With Malignant Peritoneal Mesothelioma	NCT01592383	Malignant Perit...	erlotinib hydro...	18 Years -	University of Chicago
Efficacy of a Maintenance Treatment With TALAzoparib Following First Line Platinum-based Chemotherapy in Malignant MESOthelioma	NCT04462809	Advanced Malign...	Talazoparib	18 Years -	Hospices Civils de Lyon

Spots Global Cancer Trial Database for malignant peritoneal mesothelioma