Nintedanib (BIBF 1120) in Mesothelioma

Study Overview
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Brief Summary
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This is a phase II/III confirmatory study designed to evaluate the safety and efficacy of nintedanib (BIBF 1120) in combination + (pemetrexed / cisplatin) followed by nintedanib (BIBF 1120) versus placebo + pemetrexed / cisplatin followed by placebo for the treatment of patients with unresectable malignant pleural mesothelioma.

Official Title
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LUME-Meso: Double Blind, Randomised, Multicentre, Phase II/III Study of Nintedanib in Combination With Pemetrexed / Cisplatin Followed by Continuing Nintedanib Monotherapy Versus Placebo in Combination With Pemetrexed / Cisplatin Followed by Continuing Placebo Monotherapy for the Treatment of Patients With Unresectable Malignant Pleural Mesothelioma

Conditions
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Mesothelioma

Intervention / Treatment
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* Drug: Nintedanib
* Drug: Pemetrexed
* Drug: Cisplatin
* Drug: Cisplatin
* Drug: Pemetrexed
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Histologically confirmed malignant pleural mesothelioma (MPM) (Epithelioid or biphasic subtype for Phase II patients; epithelioid subtype only for Phase III patients) 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 RECIST (Response Evaluation Criteria In Solid Tumours) 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 biphasic or sarcomatoid subtype MPM Patients with symptomatic neuropathy Radiotherapy (except extremities) within 3 months prior to baseline imaging Active brain metastases (e.g. stable for < 4 weeks) Radiographic evidence of cavitary or necrotic tumours or local invasion of major blood vessels by MPM Significant cardiovascular diseases Inadequate hematologic, renal, or hepatic function

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo + pemetrexed/cisplatin<br>Placebo controlled arm | Drug: Pemetrexed<br>* backbone chemo<br>Drug: Cisplatin<br>* backbone chemo<br>Drug: Placebo<br>* Nintedanib matching placebo<br>|
| Experimental: Nintedanib 200mg + pemetrexed/cisplatin<br>Experimental arm | Drug: Nintedanib<br>* triple kinase inhibitor; 200mg starting dose<br>Drug: Cisplatin<br>* backbone chemo<br>Drug: Pemetrexed<br>* backbone chemo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | This outcome measure presents progression-free survival. Disease progression was defined according to the modified Response Evaluation Criteria in Solid Tumours (RECIST) criteria. Progression-free survival time was calculated as the duration from the date of randomization to the date of disease progression or death, whichever occurred first. For patients with known date of progression (or death): PFS (days) = min (date of progression, date of death) - date of randomization + 1 day. For patients without progression or death, PFS was censored at the last imaging date that showed no disease progression: PFS (days, censored) = date of last imaging showing no progression - date randomization + 1 day. | From randomization until the earliest of disease progression, death or (Phase II: cut-off date of 4-March-2016; up to 889 days) (Phase III: cut-off date of 16-March-2018; up to 31 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall survival was defined as the duration of time from randomization to time of death. This is the key secondary endpoint of the trial. | From randomization until the earliest of disease progression, death or (Phase II: cut-off date of 4-March-2016; up to 889 days) (Phase III: cut-off date of 16-March-2018; up to 31 months) | 
| Objective Response According to Modified RECIST- Investigator Assessment | Objective response (best overall tumour response of confirmed complete response [CR] or confirmed partial response [PR]). Complete Response: disappearance of all target lesions Partial Response: at least a 30 % decrease in the total tumour measurement of target lesions, taking as reference the baseline total tumour measurement. Percentage of Patients with confirmed objective response is presented. This endpoint was only evaluated for Phase III part. | Tumour imaging was to be performed every 6 weeks until disease progression, death or start of subsequent anti-cancer therapy, whichever occurred earlier; up to 54 months | 
| Disease Control According to Modified RECIST- Investigator Assessment | Disease control (best overall response of confirmed CR or PR, or Stable Disease (SD) that lasted ≥36 days) according to modified RECIST. Percentage of Patients with Disease control is presented. This endpoint was only evaluated for Phase III part. | Tumour imaging was to be performed every 6 weeks until disease progression, death or start of subsequent anti-cancer therapy, whichever occurred earlier; up to 54 months |