Trial Outcomes & Findings for Nintedanib (BIBF 1120) in Mesothelioma (NCT NCT01907100)

NCT ID: NCT01907100

Last Updated: 2019-03-18

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2/PHASE3

Target enrollment

545 participants

Primary outcome timeframe

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)

Results posted on

2019-03-18

Participant Flow

Patients were initially treated with combination therapy consisting of nintedanib or placebo plus standard chemotherapy (pemetrexed/cisplatin), for a maximum of 6 cycles of 21 days duration. After completion of combination therapy, patients who had not progressed continued with nintedanib or placebo monotherapy.

All participants were screened for eligibility to participate in trial. Subjects attended specialist sites to ensure that they (the participants) met all implemented inclusion/exclusion criteria. Participants were not to be entered to trial if any of the specific entry criteria was violated. PD: Progressive Disease

Participant milestones

Participant milestones
Measure	Placebo_Phase II Phase II part: Nintedanib matching placebo 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of placebo could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.	Nintedanib_Phase II Phase II part: Nintedanib 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of Nintedanib could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.	Placebo_Phase III Phase III part: Nintedanib matching Placebo 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of placebo could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.	Nintedanib_Phase III Phase III part: Nintedanib 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of Nintedanib could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.
Overall Study STARTED	43	44	229	229
Overall Study Treated Patients	41	44	228	227
Overall Study COMPLETED	1	4	82	83
Overall Study NOT COMPLETED	42	40	147	146

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo_Phase II Phase II part: Nintedanib matching placebo 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of placebo could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.	Nintedanib_Phase II Phase II part: Nintedanib 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of Nintedanib could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.	Placebo_Phase III Phase III part: Nintedanib matching Placebo 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of placebo could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.	Nintedanib_Phase III Phase III part: Nintedanib 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of Nintedanib could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.
Overall Study PD based on modified RECIST criteria	31	32	95	92
Overall Study Withdrawal by Subject	2	5	10	13
Overall Study Protocol Violation	0	0	1	1
Overall Study Lost to Follow-up	0	0	0	1
Overall Study Not treated	2	0	1	2
Overall Study Other than reasons specified	1	0	10	6
Overall Study Adverse event (AE)	6	3	22	23
Overall Study Worsening/AE underlying cancer disease	0	0	8	8

Baseline Characteristics

Ethnicity data were not collected from any participant

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo_Phase II n=43 Participants Phase II part: Nintedanib matching placebo 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of placebo could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.	Nintedanib_Phase II n=44 Participants Phase II part: Nintedanib 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of Nintedanib could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.	Placebo_Phase III n=229 Participants Phase III part: Nintedanib matching Placebo 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of placebo could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.	Nintedanib_Phase III n=229 Participants Phase III part: Nintedanib 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of Nintedanib could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.	Total n=545 Participants Total of all reporting groups
Age, Continuous	65.9 Years STANDARD_DEVIATION 7.6 • n=43 Participants	66.4 Years STANDARD_DEVIATION 8.6 • n=44 Participants	64.3 Years STANDARD_DEVIATION 8.9 • n=229 Participants	63.6 Years STANDARD_DEVIATION 9.5 • n=229 Participants	64.3 Years STANDARD_DEVIATION 9.1 • n=545 Participants
Sex: Female, Male Female	8 Participants n=43 Participants	10 Participants n=44 Participants	60 Participants n=229 Participants	64 Participants n=229 Participants	142 Participants n=545 Participants
Sex: Female, Male Male	35 Participants n=43 Participants	34 Participants n=44 Participants	169 Participants n=229 Participants	165 Participants n=229 Participants	403 Participants n=545 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	—	—	—	—	0 Participants Ethnicity data were not collected from any participant
Ethnicity (NIH/OMB) Not Hispanic or Latino	—	—	—	—	0 Participants Ethnicity data were not collected from any participant
Ethnicity (NIH/OMB) Unknown or Not Reported	—	—	—	—	0 Participants Ethnicity data were not collected from any participant
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=43 Participants	0 Participants n=44 Participants	14 Participants n=229 Participants	12 Participants n=229 Participants	26 Participants n=545 Participants
Race (NIH/OMB) Asian	0 Participants n=43 Participants	0 Participants n=44 Participants	16 Participants n=229 Participants	14 Participants n=229 Participants	30 Participants n=545 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=43 Participants	0 Participants n=44 Participants	0 Participants n=229 Participants	0 Participants n=229 Participants	0 Participants n=545 Participants
Race (NIH/OMB) Black or African American	0 Participants n=43 Participants	0 Participants n=44 Participants	0 Participants n=229 Participants	2 Participants n=229 Participants	2 Participants n=545 Participants
Race (NIH/OMB) White	38 Participants n=43 Participants	38 Participants n=44 Participants	180 Participants n=229 Participants	185 Participants n=229 Participants	441 Participants n=545 Participants
Race (NIH/OMB) More than one race	0 Participants n=43 Participants	0 Participants n=44 Participants	0 Participants n=229 Participants	0 Participants n=229 Participants	0 Participants n=545 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=43 Participants	6 Participants n=44 Participants	19 Participants n=229 Participants	16 Participants n=229 Participants	46 Participants n=545 Participants

PRIMARY outcome

Timeframe: 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)

Population: Randomised Set: This patient set included all randomized patients.

Outcome measures

Outcome measures
Measure	Placebo n=272 Participants Nintedanib matching Placebo 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of placebo could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.	Nintedanib n=273 Participants Nintedanib 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of Nintedanib could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.
Progression-Free Survival (PFS) Phase II	5.72 Months Interval 5.19 to 8.18	9.36 Months Interval 5.55 to 12.65
Progression-Free Survival (PFS) Phase III	6.97 Months Interval 5.42 to 9.0	6.77 Months Interval 5.36 to 9.07

SECONDARY outcome

Timeframe: 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)

Population: Randomised Set: This patient set included all randomized patients.

Overall survival was defined as the duration of time from randomization to time of death. This is the key secondary endpoint of the trial.

Outcome measures

Outcome measures
Measure	Placebo n=272 Participants Nintedanib matching Placebo 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of placebo could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.	Nintedanib n=273 Participants Nintedanib 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of Nintedanib could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.
Overall Survival (OS) Phase II	14.46 Months Interval 10.41 to The 75th percentile was not reached because of insufficient number of patients with OS event thus not calculated.	18.30 Months Interval 10.91 to The 75th percentile was not reached because of insufficient number of patients with OS event thus not calculated.
Overall Survival (OS) Phase III	16.07 Months Interval 9.66 to 19.29	14.36 Months Interval 9.13 to 18.69

SECONDARY outcome

Timeframe: 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

Population: Randomised Set: This patient set included all randomized patients.

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.

Outcome measures

Outcome measures
Measure	Placebo n=229 Participants Nintedanib matching Placebo 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of placebo could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.	Nintedanib n=229 Participants Nintedanib 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of Nintedanib could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.
Objective Response According to Modified RECIST- Investigator Assessment	42.8 Percentage of participants Interval 36.3 to 49.5	45.0 Percentage of participants Interval 38.4 to 51.7

SECONDARY outcome

Timeframe: 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

Population: Randomised Set: This patient set included all randomized patients.

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.

Outcome measures

Outcome measures
Measure	Placebo n=229 Participants Nintedanib matching Placebo 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of placebo could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.	Nintedanib n=229 Participants Nintedanib 200 mg twice daily (b.i.d.) on Day 2 to 21 of each 21-day treatment course administered orally in the form of a soft gelatin capsule (100 mg or 150 mg capsules) plus standard Pemetrexed 500 mg/m2 (100 mg or 500 mg vials) and Cisplatin 75 mg/m2 (50 mL of 1 mg/ml solution) on Day 1 of each 21-day treatment course administered intravenously. If required, the dose of Nintedanib could be reduced to 150 mg b.i.d. or 100 mg b.i.d. (according to the protocol-defined dose-reduction scheme). No dose increase was allowed after a dose reduction.
Disease Control According to Modified RECIST- Investigator Assessment	92.6 Percentage of participants Interval 88.4 to 95.6	90.8 Percentage of participants Interval 86.3 to 94.2

Adverse Events

Placebo_Phase II

Serious events: 17 serious events

Other events: 41 other events

Deaths: 25 deaths

Nintedanib_Phase II

Serious events: 16 serious events

Other events: 44 other events

Deaths: 22 deaths

Placebo_Phase III

Serious events: 89 serious events

Other events: 219 other events

Deaths: 63 deaths

Nintedanib_Phase III

Serious events: 99 serious events

Other events: 218 other events

Deaths: 64 deaths

Serious adverse events

Other adverse events

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
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Restriction type: OTHER