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NCT01015118

LUME-Ovar 1: Nintedanib (BIBF 1120) or Placebo in Combination With Paclitaxel and Carboplatin in First Line Treatment of Ovarian Cancer

Completed Phase 3 Results posted Last updated 7 December 2017
What this trial tests

Phase 3 trial testing Placebo in Ovarian Neoplasms in 1,366 participants. Completed in 15 September 2016.

Timeline
17 November 2009
Primary endpoint
1 April 2013
15 September 2016

Quick facts

Lead sponsorBoehringer Ingelheim
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment1,366
Start date17 November 2009
Primary completion1 April 2013
Estimated completion15 September 2016
Sites281 locations across Italy, Finland, Poland, Denmark, Netherlands, Russia, Belgium, Sweden

Drugs / interventions tested

Conditions studied

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

18 and older, female only, with Ovarian Neoplasms or Peritoneal Neoplasms. 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.

PFS Based on Investigator Assessment According to Modified Response Evaluation Criteria in Solid Tumors, Version 1.1 (mRECIST), and Additional Clinical Criteria. Primary · First drug administration to date of disease progression or death whichever occurs first , upto 29 months

Progression free survival (PFS) is calculated as the time from randomisation to the date of disease progression, or to the date of death, whichever occurs first according to the Investigator assessment. The primary PFS analysis of this trial was performed when approximately 753 patients had experienced a PFS event Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve for each treatment arm.

GroupValue95% CI
Nintedanib17.211.1 – 32.5
Placebo16.610.8 – 30.4
PFS Based on Investigator Assessment According to Modified Response Evaluation Criteria in Solid Tumors, Version 1.1 (mRECIST), and Additional Clinical Criteria (Follow up Analysis). Primary · First drug administration to date of disease progression or death whichever occurs first until final Data Base Lock (DBL) 26September16, upto 62 months

Follow-up analysis was conducted at the time of overall survival analysis. Progression free survival (PFS) is calculated as the time from randomisation to the date of disease progression, or to the date of death, whichever occurs first according to the Investigator assessment. Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve for each treatment arm.

GroupValue95% CI
Nintedanib17.611.1 – 38.0
Placebo16.610.8 – 37.3
PFS Based on Investigator Assessment According to mRECIST Version 1.1 (Key Secondary Endpoint). Secondary · First drug administration to date of disease progression or death whichever occurs first , upto 29 months

Progression free survival is calculated as the time from randomisation to the date of disease progression, or to the date of death, whichever occurs first based on the Investigator assessment according to Modified Response Evaluation Criteria (mRECIST), version 1.1. The primary PFS analysis of this trial was performed when approximately 753 patients had experienced a PFS event. Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve for each treatment arm.

GroupValue95% CI
Nintedanib18.311.1 – 32.5
Placebo16.610.8 – 30.4
PFS Based on Investigator Assessment According to mRECIST Version 1.1 (Key Secondary Endpoint - Follow up Analysis). Secondary · First drug administration to date of disease progression or death whichever occurs first until final Data Base Lock (DBL) 26September16, upto 62 months

Follow-up analysis was conducted at the time of overall survival analysis. Progression free survival is calculated as the time from randomisation to the date of disease progression, or to the date of death, whichever occurs first based on the Investigator assessment according to Modified Response Evaluation Criteria (mRECIST), version 1.1. Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve for each treatment arm.

GroupValue95% CI
Nintedanib18.411.1 – 38.5
Placebo16.610.8 – 37.3
Overall Survival Secondary · First drug administration to date of death until final DBL 26September16, upto 62 months

Overall survival is defined as time from randomization to date of death (irrespective of reason). Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve for each treatment arm.

GroupValue95% CI
Nintedanib62.030.0 – NA
Placebo62.830.6 – NA
Time to CA-125 Tumour Marker Progression Secondary · First drug administration until final DBL 26September16, upto 62 months

Time to tumour-marker progression was defined as the time from randomisation until the date when Carbohydrate (cancer) antigen (CA-125) values increased to higher than twice the nadir value. CA-125 \>=2 x nadir in case nadir value \> Upper limit of normal (ULN) or CA-125 \>=2 x ULN in case nadir value \<= ULN.

GroupValue95% CI
Nintedanib16.610.6 – 47.0
Placebo14.18.6 – 42.6
Objective Response Based on Investigator Assessment Secondary · First drug administration until final DBL 26September16, upto 62 months

Objective tumour response defined as either complete response \[CR\] or partial response \[PR\] in patients with at least 1 target lesion reported at baseline

GroupValue95% CI
Nintedanib74.3
Placebo70.2
Change in Abdominal/Gastro-intestinal Symptoms Over Time Secondary · First drug administration until final DBL 26September16, upto 62 months

Change in abdominal/gastro-intestinal over time was calculated on symptoms (scale composite of items 31 to 37 of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Module for Ovarian Cancer 28 (EORTC QLQ OV-28). As specified in the EORTC scoring manual, for each scale or item, a linear transformation was applied to standardize the raw score to a range from 0 to 100 (high scores represent a high/severe level of symptomatology). Mean presented is Adjusted mean. Adjusted for the stratification factors macroscopic residual postoperative tumour at baselin

GroupValue95% CI
Nintedanib24.63± 0.49
Placebo19.34± 0.64
Change in Global Health Status/ Quality of Life (QoL) Scale Over Time. Secondary · First drug administration until final DBL 26September16, upto 62 months

Change in Global Health Status/ Quality of life (QoL) over time was calculated on Global Health Status/QoL scale (composite of items 29 and 30 of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-30 (EORTC QLQ-C30) as a general measure. As specified in the EORTC scoring manual, for each scale or item, a linear transformation was applied to standardize the raw score to a range from 0 to 100 (high scores represent a high/healthy level of functioning). Mean presented is Adjusted mean. Adjusted for the stratification factors macroscopic residual postope

GroupValue95% CI
Nintedanib68.79± 0.48
Placebo70.67± 0.65

Adverse events — posted to ClinicalTrials.gov

Time frame: First drug administration until data cut-off 26September16, up to 62 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 157/450 (35%)
Deaths:
Nintedanib
Serious: 379/902 (42%)
Deaths:

Serious adverse events (376 terms)

ReactionSystemPlaceboNintedanib
DiarrhoeaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
Abdominal painGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
PyrexiaGeneral disorders
ThrombocytopeniaBlood and lymphatic system disorders
DehydrationMetabolism and nutrition disorders
Febrile neutropeniaBlood and lymphatic system disorders
IleusGastrointestinal disorders
General physical health deteriorationGeneral disorders
Urinary tract infectionInfections and infestations
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
AscitesGastrointestinal disorders
ConstipationGastrointestinal disorders
AstheniaGeneral disorders
Small intestinal obstructionGastrointestinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
FatigueGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Drug hypersensitivityImmune system disorders
LeukopeniaBlood and lymphatic system disorders
PancytopeniaBlood and lymphatic system disorders
Abdominal pain upperGastrointestinal disorders
Other adverse events (58 terms — click to expand)

ReactionSystemPlaceboNintedanib
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
AlopeciaSkin and subcutaneous tissue disorders
NeutropeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
FatigueGeneral disorders
AnaemiaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
ConstipationGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Aspartate aminotransferase increasedInvestigations
Peripheral sensory neuropathyNervous system disorders
MyalgiaMusculoskeletal and connective tissue disorders
Neuropathy peripheralNervous system disorders
Decreased appetiteMetabolism and nutrition disorders
LeukopeniaBlood and lymphatic system disorders
AstheniaGeneral disorders
HeadacheNervous system disorders
Urinary tract infectionInfections and infestations
DysgeusiaNervous system disorders
Abdominal pain upperGastrointestinal disorders
HypertensionVascular disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
InsomniaPsychiatric disorders
ParaesthesiaNervous system disorders
Pain in extremityMusculoskeletal and connective tissue disorders
RashSkin and subcutaneous tissue disorders
HypomagnesaemiaMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
DyspepsiaGastrointestinal disorders
DizzinessNervous system disorders
Blood alkaline phosphatase increasedInvestigations
Neutrophil count decreasedInvestigations
NasopharyngitisInfections and infestations
Hot flushVascular disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
CystitisInfections and infestations

Most-reported serious reactions: Diarrhoea, Anaemia, Vomiting, Abdominal pain, Neutropenia, Nausea, Pyrexia, Thrombocytopenia.

Data from ClinicalTrials.gov NCT01015118 adverse events section.

Sponsor's own description

The trial will be performed to evaluate if BIBF 1120 in combination with paclitaxel and carboplatin is more effective than placebo in combination with paclitaxel and carboplatin in first-line treatment of patients with advanced ovarian cancer. Safety information about BIBF1120/paclitaxel/carboplatin will be obtained.

Publications & conference data

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

  1. Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis.
    Wollin L, Wex E, Pautsch A, Schnapp G, et al · · 2015 · cited 698× · PMID 25745043 · DOI 10.1183/09031936.00174914
  2. Advances in ovarian cancer therapy.
    Cortez AJ, Tudrej P, Kujawa KA, Lisowska KM. · · 2018 · cited 417× · PMID 29249039 · DOI 10.1007/s00280-017-3501-8
  3. Latest research and treatment of advanced-stage epithelial ovarian cancer.
    Coleman RL, Monk BJ, Sood AK, Herzog TJ. · · 2013 · cited 412× · PMID 23381004 · DOI 10.1038/nrclinonc.2013.5
  4. Tumor Microenvironment in Ovarian Cancer: Function and Therapeutic Strategy.
    Yang Y, Yang Y, Yang J, Zhao X, et al · · 2020 · cited 168× · PMID 32850861 · DOI 10.3389/fcell.2020.00758
  5. Significance of vascular endothelial growth factor in growth and peritoneal dissemination of ovarian cancer.
    Masoumi Moghaddam S, Amini A, Morris DL, Pourgholami MH. · · 2012 · cited 155× · PMID 22101807 · DOI 10.1007/s10555-011-9337-5
  6. Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial.
    du Bois A, Kristensen G, Ray-Coquard I, Reuss A, et al · · 2016 · cited 151× · PMID 26590673 · DOI 10.1016/s1470-2045(15)00366-6
  7. Resistance and escape from antiangiogenesis therapy: clinical implications and future strategies.
    Bottsford-Miller JN, Coleman RL, Sood AK. · · 2012 · cited 151× · PMID 23008289 · DOI 10.1200/jco.2012.41.9242
  8. Tumor stroma as targets for cancer therapy.
    Zhang J, Liu J. · · 2013 · cited 139× · PMID 23064233 · DOI 10.1016/j.pharmthera.2012.10.003

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Trials by the same sponsor.

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