Unresectable Malignant Pleural Mesothelioma MedDRA version: 20.0 Level: PT Classification code 10059518 Term: Pleural mesothelioma malignant System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Vargatef
Product Name: Nintedanib 100 mg capsules
Product Code: BIBF 1120
Pharmaceutical Form: Capsule, soft
INN or Proposed
Sponsors
Boehringer Ingelheim Pharma GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically confirmed malignant pleural mesothelioma (MPM) (subtype: epithelioid or biphasic for Phase II or epithelioid only for Phase III) - Life expectancy of at least 3 months in the opinion of the investigator - Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 - Measurable disease according to modified Response Evaluation Criteria In Solid Tumours (RECIST) criteria 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 183 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 354
Exclusion criteria
Exclusion criteria: - Previous systemic chemotherapy for MPM - Prior treatment with nintedanib or any other prior line of therapy - Phase II patients with sarcomatoid subtype MPM or Phase III Patients with sarcomatoid or biophasic subtype - Radiotherapy (except extremities) within 3 months prior to baseline imaging - Patients that may be eligible for or being considered for radical resection or elective surgery during the course of the study. - Radical surgery within 4 weeks prior to randomisation - Active brain metastases (e.g. stable for < 4 weeks) - Therapeutic anticoagulation or anti-platelet therapy (except for lowdose therapy with acetylsalicylic acid < 325 mg per day) - Major injuries within the past 4 weeks prior to randomisation with incomplete wound healing - Other malignancies within 3 years prior to screening other than basal cell skin cancer or carcinoma in situ of the cervix
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the randomised, parallel-controlled Phase II/III study is to evaluate the safety and efficacy in terms of progression-free survival of nintedanib + pemetrexed / cisplatin followed by nintedanib (arm A) versus placebo + pemetrexed / cisplatin followed by placebo (arm B), as first line treatment for patients with unresectable MPM. ; Secondary Objective: The key secondary objective is to evaluate OS in patients treated with the nintedanib regimen (arm A) versus the placebo regimen (arm B). Further secondary objectives are to evaluate the objective tumour response rate and to evaluate the disease control rate. Further objectives in this trial are to evaluate related measures of tumour response, to assess the percentage changes from baseline in forced vital capacity (FVC)(Phase II part only), to obtain information on health-related quality of life (HRQoL)[ Phase III part only ], and to examine exposure to nintedanib in patients with unresectable MPM. In addition, biological specimens will be collected for the evaluation of molecular markers and possible correlation with treatment outcome ;Primary end point(s): 1. Progression free survival measured from the time of randomisation to the time of disease progression or death of any cause, whichever occurs earlier; Timepoint(s) of evaluation of this end point: For Phase II, the observation period for PFS is defined from randomisation until the earliest of disease progression, death or the cut-off of 04-Mar-2016 for the primary PFS analysis. For Phase III, the observation period for PFS will continue until the earliest of disease progression, death or until approximately 199 PFS events have occurred for Phase III patients or untill approximately 23 months has elapsed since the first Phase III patients was randomised. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: For Phase II, the observation period for OS is until the earliest of death or until approximately 61 Phase II patients have died, whichever occurs first. For Phase III, the observation period for OS is from randomisation until the earliest case of death or until approximately 279 to 346 (depending on the event reassessment) OS events have occured for Phase III patients or until approximately 54 months has elapsed since the first Phase III patient was randomised. If the trial is declared positive also for OS at the time of the interim Phase III OS analysis, the observation period for OS will continue untill approximately 199 PFS events have occurred. Final evaluation: November 2020 ; Secondary end point(s): - Overall survival measured from the time of randomisation to the time of death of any cause (key secondary endpoint) - Objective response according to modified RECIST analysed by objective response rate - Disease control according to modified RECIST analysed by disease control rate | — |
Countries
Argentina, Australia, Austria, Belgium, Canada, Chile, Croatia, Czech Republic, Denmark, Egypt, France, Germany, Israel, Italy, Japan, Mexico, Netherlands, Norway, Poland, Portugal, Russian Federation, South Africa, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States
Contacts
Public ContactQRPE PSC CT Information Disclosure
Boehringer Ingelheim Pharma GmbH & Co. KG
Outcome results
None listed