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NCT01907100

Nintedanib (BIBF 1120) in Mesothelioma

Terminated Phase 2, PHASE3 Results posted Last updated 18 March 2019
What this trial tests

Phase 2, PHASE3 trial testing Nintedanib in Mesothelioma in 545 participants. Terminated before completion.

Timeline
19 September 2013
Primary endpoint
16 March 2018
31 August 2018

Quick facts

Lead sponsorBoehringer Ingelheim
PhasePhase 2, PHASE3
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment545
Start date19 September 2013
Primary completion16 March 2018
Estimated completion31 August 2018
Sites123 locations across Italy, Japan, Poland, Croatia, Denmark, Netherlands, Russia, Turkey (Türkiye)

Drugs / interventions tested

Conditions studied

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

18 and older, any sex, with Mesothelioma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression-Free Survival (PFS) Primary · 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)

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 progr

Phase II
GroupValue95% CI
Placebo5.725.19 – 8.18
Nintedanib9.365.55 – 12.65
Phase III
GroupValue95% CI
Placebo6.975.42 – 9.00
Nintedanib6.775.36 – 9.07
Overall Survival (OS) Secondary · 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)

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

Phase II
GroupValue95% CI
Placebo14.4610.41 – NA
Nintedanib18.3010.91 – NA
Phase III
GroupValue95% CI
Placebo16.079.66 – 19.29
Nintedanib14.369.13 – 18.69
Objective Response According to Modified RECIST- Investigator Assessment Secondary · 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

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.

GroupValue95% CI
Placebo42.836.3 – 49.5
Nintedanib45.038.4 – 51.7
Disease Control According to Modified RECIST- Investigator Assessment Secondary · 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 (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.

GroupValue95% CI
Placebo92.688.4 – 95.6
Nintedanib90.886.3 – 94.2

Adverse events — posted to ClinicalTrials.gov

Time frame: SAE & Non SAE: From first dose until 28 days (Phase II) or 30 days (Phase III) after last dose, up to approximately (approx.) 30 months in Phase II and approx. 32 months in Phase III. All-cause mortality: From randomization until end of follow-up, up to approx. 30 months in Phase II and approx. 32 months in Phase III. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo_Phase II
Serious: 17/41 (41%)
Deaths: 25/43
Nintedanib_Phase II
Serious: 16/44 (36%)
Deaths: 22/44
Placebo_Phase III
Serious: 89/228 (39%)
Deaths: 63/229
Nintedanib_Phase III
Serious: 99/227 (44%)
Deaths: 64/229

Serious adverse events (168 terms)

ReactionSystemPlacebo_Phase IINintedanib_Phase IIPlacebo_Phase IIINintedanib_Phase III
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
Acute kidney injuryRenal and urinary disorders
AnaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
NeutropeniaBlood and lymphatic system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
PneumoniaInfections and infestations
Chest painGeneral disorders
Febrile neutropeniaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
General physical health deteriorationGeneral disorders
Lower respiratory tract infectionInfections and infestations
Renal failureRenal and urinary disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Febrile bone marrow aplasiaBlood and lymphatic system disorders
FatigueGeneral disorders
Blood creatinine increasedInvestigations
Deep vein thrombosisVascular disorders
Mucosal inflammationGeneral disorders
Neutropenic sepsisInfections and infestations
Other adverse events (76 terms — click to expand)

ReactionSystemPlacebo_Phase IINintedanib_Phase IIPlacebo_Phase IIINintedanib_Phase III
NauseaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
FatigueGeneral disorders
AstheniaGeneral disorders
Alanine aminotransferase increasedInvestigations
DyspnoeaRespiratory, thoracic and mediastinal disorders
CoughRespiratory, thoracic and mediastinal disorders
Aspartate aminotransferase increasedInvestigations
LeukopeniaBlood and lymphatic system disorders
Neutrophil count decreasedInvestigations
DysgeusiaNervous system disorders
Blood creatinine increasedInvestigations
HypertensionVascular disorders
Gamma-glutamyltransferase increasedInvestigations
TinnitusEar and labyrinth disorders
Abdominal painGastrointestinal disorders
Chest painGeneral disorders
Weight decreasedInvestigations
HeadacheNervous system disorders
RashSkin and subcutaneous tissue disorders
StomatitisGastrointestinal disorders
Mucosal inflammationGeneral disorders
PyrexiaGeneral disorders
DyspepsiaGastrointestinal disorders
HypomagnesaemiaMetabolism and nutrition disorders
ParaesthesiaNervous system disorders
HiccupsRespiratory, thoracic and mediastinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
Lacrimation increasedEye disorders
DizzinessNervous system disorders
Neuropathy peripheralNervous system disorders
White blood cell count decreasedInvestigations
Blood magnesium decreasedInvestigations
Oedema peripheralGeneral disorders

Most-reported serious reactions: Pulmonary embolism, Pyrexia, Acute kidney injury, Anaemia, Diarrhoea, Vomiting, Dehydration, Neutropenia.

Data from ClinicalTrials.gov NCT01907100 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Inhibition of FGF-FGFR and VEGF-VEGFR signalling in cancer treatment.
    Liu G, Chen T, Ding Z, Wang Y, et al · · 2021 · cited 131× · PMID 33655556 · DOI 10.1111/cpr.13009
  2. Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial.
    Scagliotti GV, Gaafar R, Nowak AK, Nakano T, et al · · 2019 · cited 108× · PMID 31103412 · DOI 10.1016/s2213-2600(19)30139-0
  3. Scientific Advances and New Frontiers in Mesothelioma Therapeutics.
    Mutti L, Peikert T, Robinson BWS, Scherpereel A, et al · · 2018 · cited 85× · PMID 29966799 · DOI 10.1016/j.jtho.2018.06.011
  4. Malignant Pleural Mesothelioma: State-of-the-Art on Current Therapies and Promises for the Future.
    Nicolini F, Bocchini M, Bronte G, Delmonte A, et al · · 2019 · cited 68× · PMID 32039010 · DOI 10.3389/fonc.2019.01519
  5. Targeting FGFR for cancer therapy.
    Zhang P, Yue L, Leng Q, Chang C, et al · · 2024 · cited 64× · PMID 38831455 · DOI 10.1186/s13045-024-01558-1
  6. Progress in the Management of Malignant Pleural Mesothelioma in 2017.
    McCambridge AJ, Napolitano A, Mansfield AS, Fennell DA, et al · · 2018 · cited 62× · PMID 29524617 · DOI 10.1016/j.jtho.2018.02.021
  7. Malignant pleural mesothelioma: an update on diagnosis and treatment options.
    Kondola S, Manners D, Nowak AK. · · 2016 · cited 39× · PMID 26873306 · DOI 10.1177/1753465816628800
  8. Phase II Trial of Cediranib in Combination With Cisplatin and Pemetrexed in Chemotherapy-Naïve Patients With Unresectable Malignant Pleural Mesothelioma (SWOG S0905).
    Tsao AS, Miao J, Wistuba II, Vogelzang NJ, et al · · 2019 · cited 38× · PMID 31386610 · DOI 10.1200/jco.19.00269

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing