EORTC-08112

EORTC

Avenue Emmanuel Mounier 83/11, Brussels, Belgium, 1200

Regulatory Affairs Department, European Organisation for the Research and Treatment of Cancer, 0032 27741511, regulatory@eortc.org

Regulatory Affairs Department, European Organisation for the Research and Treatment of Cancer, 0032 27741511, regulatory@eortc.org

No

No

No

Final

30 Apr 2023

Yes

30 Apr 2023

Yes

12 Oct 2023

Yes

the primary objective is to evaluate activity in terms of progression-free survival of nintedanib versus placebo as switch maintenance after first line chemotherapy treatment for patients with unresectable Malignant Pleural Mesothelioma

Safety data were reviewed within EORTC Headquarters on a regular basis as part of the Medical Review process. Safety information was included in trial status reports which served as a basis of discussion during EORTC Group meetings.

15 May 2017

No

Yes

United Kingdom: 26

Belgium: 5

France: 1

Italy: 5

37

11

0

0

0

0

0

0

7

30

0

Switch maintenance treament and placebo (overall period)

Randomised - controlled

This is a triple blind study. The patient, the investigator and study team at site and the EORTC Headquarters study team will remain blinded to treatment allocation up to the database lock for the final analysis of the primary endpoint. However, at any time during the trial, in case of a safety concern affecting an individual patient, the site investigator can request the unblinding of that patient.

Yes

Nintedanib

BIBF 1120

Capsule, soft

Oral use

400 mg (200 mg twice daily), continuous daily dosing until progression of disease or until criteria for interruption of treatment are met . Dose reductions as needed were used in order to manage undue toxicities. Dose reduction steps: 200 mg twice daily - 150 mg twice daily - 100 mg twice daily - Stop protocol treatment. If the dose of nintedanib had to be reduced due to adverse events it will stay on the lower dose level for the entire time of administration, reescalation is not allowed

No investigational medicinal product assigned in this arm

Nintedanib

Placebo

Per Protocol

All patients who are eligible and have started their allocated treatment (at least one dose of the study drug(s) in chemotherapy trials)

Safety

All patients who have started their allocated treatment (at least one dose of the study drug(s) in chemotherapy trials)

Nintedanib

Placebo

Per Protocol

All patients who are eligible and have started their allocated treatment (at least one dose of the study drug(s) in chemotherapy trials)

Safety

All patients who have started their allocated treatment (at least one dose of the study drug(s) in chemotherapy trials)

Progression Free Survival (PFS) is defined as the time interval between the date of randomization and the date of disease progression, recurrence or death, whichever comes first. If neither event has been observed, then the patient is censored at the date of the last follow up examination

Primary

Originally planned after reaching 95 PFS events. The accrual was stopped prematurely due to the low accrual rate February 5th 2021 . The analysis was performed on the 37 eligible at the clinical cut-off date of the 30th of April 2023.

Due to poor accrual, and recruiting only 37 patients (36 in the per-protocol analysis set) rather than the planned 114 patients, the statistical analysis of this (primary) endpoint is only descriptive. The analysis is performed on the per-protocol population. HR values smaller than 1 indicate longer PFS in the experimental arm. HR values larger than 1 indicate shorter PFS in the experimental arm.

Nintedanib v Placebo

36

Pre-specified

2.25

2-sided

The overall response rate is defined as an overall rate including patients with documented complete response (CR) or partial response (PR) where CR and PR are defined according to the RECIST criteria. The baseline for this assessment is set after the induction chemotherapy and within 3 weeks prior to randomization.

Secondary

Between the 24th April 2018 and the 3rd of February 2021

The overall response rate is defined as an overall rate including patients with documented complete response or partial response. Stable disease, progressive disease, early death and unknown(missing) response status are considered as failures to respond to treatment.

Placebo v Nintedanib

36

Pre-specified

0

2-sided

The overall response rate is defined as an overall rate including patients with documented complete response or partial response. Stable disease, progressive disease, early death and unknown(missing) response status are considered as failures to respond to treatment.

Placebo v Nintedanib

36

Pre-specified

5.6

2-sided

Overall survival time is computed from date of registration until date of death from any cause. If no death has been observed, then the patient is censored at the last date known to be alive. The analysis is performed on the per-protocol population The value 99999 is used when the upper limit of a confidence interval has not been reached

Secondary

xxx

HR values larger than 1 indicate shorter Overall Survival in the experimental arm.

Nintedanib v Placebo

36

Pre-specified

2.27

2-sided

Time to treatment Failure (TTF) is defined as the time interval between the date of randomization and discontinuation for any reason, including disease progression, treatment toxicity, normal completion, patient preference, or death. If no event has been observed, then the patient is censored at the last date of disease evaluation.

Secondary

xxx

HR values larger than 1 indicate shorter time-to-treatment failure in the experimental arm.

Nintedanib v Placebo

36

Pre-specified

2.56

2-sided

The number of patients who had specific adverse events in the period between the randomization and the time of treatment (including placebo treatment) discontinuation was reported. The maximum was ...

Adverse events are evaluated using CTC grading. Serious adverse events were defined following the Good Clinical Practice Guideline. Adverse events are reported as belonging to the treatment period if the adverse event start date falls on the first day of treatment and up till the date of last treatment administration + 30 days.

4

Nintedanib

Placebo