Nintedanib (BIBF 1120) in Mesothelioma

• ClinicalTrials.gov Identifier: NCT01907100
• Recruitment Status: Terminated
• First Posted: July 24, 2013
• Results First Posted: March 18, 2019
• Last Update Posted: March 18, 2019
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Tracking Information

• First Submitted Date: July 22, 2013
• First Posted Date: July 24, 2013
• Results First Submitted Date: September 11, 2018
• Results First Posted Date: March 18, 2019
• Last Update Posted Date: March 18, 2019
• Actual Study Start Date: September 19, 2013
• Actual Primary Completion Date: March 16, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 15, 2019)

Progression-Free Survival (PFS) [ Time Frame: 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 progression: PFS (days, censored) = date of last imaging showing no progression - date randomization + 1 day.

• Original Primary Outcome Measures (submitted: July 22, 2013): Progression free survival measured from the time of randomisation to the time of disease progression or death of any cause, whichever occurs earlier [ Time Frame: up to 3 year ]

Current Secondary Outcome Measures (submitted: March 15, 2019)

• Overall Survival (OS) [ Time Frame: 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.
• Objective Response According to Modified RECIST- Investigator Assessment [ Time Frame: 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.
• Disease Control According to Modified RECIST- Investigator Assessment [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: July 22, 2013)

• Overall survival measured from the time of randomisation to the time of death of any cause [ Time Frame: up to 4 years ]
• Change from baseline in forced vital capacity (pulmonary function) [ Time Frame: up to 3 year ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Nintedanib (BIBF 1120) in Mesothelioma
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double; Primary Purpose: Treatment
• Condition: Mesothelioma

Intervention

• Drug: Nintedanib
  triple kinase inhibitor; 200mg starting dose
• Drug: Pemetrexed
  backbone chemo
• Drug: Cisplatin
  backbone chemo
• Drug: Placebo
  Nintedanib matching placebo

Study Arms

• Placebo Comparator: Placebo + pemetrexed/cisplatin
  Placebo controlled arm
  Interventions:

  • Drug: Pemetrexed
  • Drug: Cisplatin
  • Drug: Placebo
• Experimental: Nintedanib 200mg + pemetrexed/cisplatin
  Experimental arm
  Interventions:

  • Drug: Nintedanib
  • Drug: Cisplatin
  • Drug: Pemetrexed

• Publications *: Scagliotti GV, Gaafar R, Nowak AK, Nakano T, van Meerbeeck J, Popat S, Vogelzang NJ, Grosso F, Aboelhassan R, Jakopovic M, Ceresoli GL, Taylor P, Orlandi F, Fennell DA, Novello S, Scherpereel A, Kuribayashi K, Cedres S, Sorensen JB, Pavlakis N, Reck M, Velema D, von Wangenheim U, Kim M, Barrueco J, Tsao AS. 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. Lancet Respir Med. 2019 Jul;7(7):569-580. doi: 10.1016/S2213-2600(19)30139-0. Epub 2019 May 15.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: June 13, 2018): 545
• Original Estimated Enrollment (submitted: July 22, 2013): 86
• Actual Study Completion Date: August 31, 2018
• Actual Primary Completion Date: March 16, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Canada, Chile, Croatia, Czechia, Denmark, Egypt, France, Germany, Israel, Italy, Japan, Mexico, Netherlands, Norway, Poland, Portugal, Russian Federation, South Africa, Spain, Sweden, Turkey, United Kingdom, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT01907100
• Other Study ID Numbers: 1199.93; 2012-005201-48 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Boehringer Ingelheim
• Original Responsible Party: Same as current
• Current Study Sponsor: Boehringer Ingelheim
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Boehringer Ingelheim; Boehringer Ingelheim

• PRS Account: Boehringer Ingelheim
• Verification Date: March 2019