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NCT02451007

Evaluation of the Effect of Lurbinectedin (PM01183) on Cardiac Repolarization in Patients With Selected Solid Tumors

Completed Phase 2 Results posted Last updated 19 November 2019
What this trial tests

Phase 2 trial testing lurbinectedin (PM01183) in Solid Tumors in 39 participants. Completed in 19 August 2016.

Timeline
12 August 2015
Primary endpoint
19 August 2016
19 August 2016

Quick facts

Lead sponsorPharmaMar
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposeother
Enrollment39
Start date12 August 2015
Primary completion19 August 2016
Estimated completion19 August 2016
Sites16 locations across United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

PharmaMar — full company profile →

Who can join

Under 65, any sex, with Solid Tumors. 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.

Change in QTcF (QT Corrected According to Fridericia's Formula) Primary · Scheduled post-baseline ECG time points were taken 5-10 min before their time-matched PK samples: i.e., 5 min before EOI, 30 min, 1, 3, 24, 72 and 168 hours after EOI of Cycle 1, and 5 min before EOI, 30 min, 1, 3 and 168 hours after EOI of Cycle 2.

ΔQTCF (Change in QTcF); EOI (end of infusion); LSM (Least Square Means); PK (Pharmacokinetic(s)). On Day 1 (D1) of Cycle 1 (C1), LSM ΔQTcF should have low difference values, without any clear trend to change with time. Therefore, the upper bound (UB) of the (two-sided) 90%Confidence Interval (CI) at all time points had to be less than the protocol-specified cut-off of 20 ms at each time point. If so, non-inferiority of any ECG time point to baseline with respect of QTc prolongation could be concluded

Cycle 1 - 5 min before EOI
GroupValue95% CI
Group A - Lurbinectedin (PM01183)3.321.12 – 5.51
Cycle 1 - 30 min after EOI
GroupValue95% CI
Group A - Lurbinectedin (PM01183)1.76-0.41 – 3.93
Cycle 1 - 1 hour after EOI
GroupValue95% CI
Group A - Lurbinectedin (PM01183)1.84-1.02 – 4.69
Cycle 1 - 3 hour after EOI
GroupValue95% CI
Group A - Lurbinectedin (PM01183)1.32-1.40 – 4.05
Cycle 1 - 24 hour after EOI
GroupValue95% CI
Group A - Lurbinectedin (PM01183)-8.24-11.2 – -5.26
Cycle 1 - 72 hour after EOI
GroupValue95% CI
Group A - Lurbinectedin (PM01183)-12.4-15.4 – -9.39
Cycle 1 - 168 hour after EOI
GroupValue95% CI
Group A - Lurbinectedin (PM01183)-5.20-7.98 – -2.41
Cycle 2 - Before start of infusion
GroupValue95% CI
Group A - Lurbinectedin (PM01183)-0.46-3.27 – 2.35
Relationship Between ΔQTcF and Time-matched Lurbinectedin Plasma Concentrations (Plasma Concentration) Secondary · Through study completion, each patient had to be followed for 2 cycles (1 cycle =3 weeks)

ΔQTcF (Change from Baseline in QT Corrected According to Fridericia's Formula); CI (Confidence Interval); Cmax (Maximum Plasma Concentration). Table below details the results of the linear mixed effects model to quantify the relationship between the lurbinectedin plasma concentrations and ΔQTcF and Predicted ΔQTcF and 90% CI at mean lurbinectedin Cmax.

GroupValue95% CI
Group A - Lurbinectedin (PM01183)2.061.42 – 2.71
Relationship Between ΔQTcF and Time-matched Lurbinectedin Plasma Concentrations (Predicted ΔQTcF) Secondary · Through study completion, each patient had to be followed for 2 cycles (1 cycle =3 weeks)

ΔQTcF (Change from Baseline in QT Corrected According to Fridericia's Formula); CI (Confidence Interval); Cmax (Maximum Plasma Concentration). Table below details the results of the linear mixed effects model to quantify the relationship between the lurbinectedin plasma concentrations and ΔQTcF and Predicted ΔQTcF and 90% CI at mean lurbinectedin Cmax.

GroupValue95% CI
Group A - Lurbinectedin (PM01183)2.940.79 – 5.10
Relationship Between ΔQTcF and Time-matched Lurbinectedin Plasma Concentrations (Intercept) Secondary · Through study completion, each patient had to be followed for 2 cycles (1 cycle =3 weeks)

ΔQTcF (Change from Baseline in QT Corrected According to Fridericia's Formula); CI (Confidence Interval); Cmax (Maximum Plasma Concentration). Table below details the results of the linear mixed effects model to quantify the relationship between the lurbinectedin plasma concentrations and ΔQTcF and Predicted ΔQTcF and 90% CI at mean lurbinectedin Cmax.

GroupValue95% CI
Group A - Lurbinectedin (PM01183)-6.40-8.44 – -4.35

Adverse events — posted to ClinicalTrials.gov

Time frame: Through study completion, each patient had to be followed for 2 cycles (1 cycle =3 weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Group A - Lurbinectedin (PM01183)
Serious: 9/39 (23%)
Deaths: 13/39

Serious adverse events (12 terms)

ReactionSystemGroup A - Lurbinectedin (P…
Abdominal painGastrointestinal disorders
Blood calcium decreasedInvestigations
Blood phosphorus decreasedInvestigations
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
AspirationRespiratory, thoracic and mediastinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
Facial paralysisNervous system disorders
General physical health deteriorationGeneral disorders
Small intestinal obstructionGastrointestinal disorders
CholangitisHepatobiliary disorders
Device related infectionInfections and infestations
Skin infectionInfections and infestations
Other adverse events (15 terms — click to expand)

ReactionSystemGroup A - Lurbinectedin (P…
NauseaGastrointestinal disorders
FatigueGeneral disorders
ConstipationGastrointestinal disorders
VomitingGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
HeadacheNervous system disorders
PyrexiaGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
AnaemiaBlood and lymphatic system disorders
InsomniaPsychiatric disorders
Abdominal pain upperGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
DysgeusiaNervous system disorders
HyponatraemiaMetabolism and nutrition disorders

Most-reported serious reactions: Abdominal pain, Blood calcium decreased, Blood phosphorus decreased, Acute respiratory failure, Aspiration, Febrile neutropenia, Facial paralysis, General physical health deterioration.

Data from ClinicalTrials.gov NCT02451007 adverse events section.

Sponsor's own description

Study to assess the potential effects of lurbinectedin (PM01183) at a therapeutic dose on the duration of the QTc interval, measured by electrocardiograms (ECGs), to characterize the PM01183 plasma concentration/QTc relationship, and to explore related ECG parameters in patients with selected solid tumors.

Publications & conference data

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

  1. A pivotal bridging study of lurbinectedin as second-line therapy in Chinese patients with small cell lung cancer.
    Cheng Y, Wu C, Wu L, Zhao J, et al · · 2024 · cited 5× · PMID 38351146 · DOI 10.1038/s41598-024-54223-5
  2. Effect of lurbinectedin on the QTc interval in patients with advanced solid tumors: an exposure-response analysis.
    Fudio S, Tabernero J, Subbiah V, Chawla SP, et al · · 2021 · cited 4× · PMID 33108504 · DOI 10.1007/s00280-020-04153-6

Verify or expand the search:

Other trials of lurbinectedin (PM01183)

Trials testing the same drug.

Other recruiting trials for Solid Tumors

Currently open trials in the same condition.

Other PharmaMar trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02451007.

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