Evaluation of the Effect of Lurbinectedin (PM01183) on Cardiac Repolarization in Patients With Selected Solid Tumors
- Registration Number
- NCT02451007
- Lead Sponsor
- PharmaMar
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 39
- Voluntarily signed and dated informed consent
- Normal cardiac conduction and function (centrally read)
- Blood pressure between 90 and 150 mmHg systolic, inclusive, and not higher than 90 mmHg diastolic.
- Specific serum electrolyte levels
- Age > 65 years
- Performance status = 2 [Eastern Cooperative Oncology Group (ECOG)]
- Heart rhythm disturbances
- Significant ischemic coronary disease, heart failure, myocardial infarction, or unstable angina within the last six months.
- Prior exposure to anthracyclines at a cumulative dose of doxorubicin (or equivalent) > 450 mg/m²
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description A (lurbinectedin) lurbinectedin (PM01183) lurbinectedin (PM01183) 4 mg vials of powder for concentrate for solution for infusion
- Primary Outcome Measures
Name Time Method Change in QTcF (QT Corrected According to Fridericia's Formula) 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
- Secondary Outcome Measures
Name Time Method Relationship Between ΔQTcF and Time-matched Lurbinectedin Plasma Concentrations (Plasma Concentration) 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.Relationship Between ΔQTcF and Time-matched Lurbinectedin Plasma Concentrations (Predicted ΔQTcF) 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.Relationship Between ΔQTcF and Time-matched Lurbinectedin Plasma Concentrations (Intercept) 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.
Trial Locations
- Locations (16)
Sarcoma Oncology Research Center
🇺🇸Santa Monica, California, United States
Hospital Universitari I Politècnic La Fe
🇪🇸Valencia, Spain
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
Dana Farber Cancer lnstitute
🇺🇸Boston, Massachusetts, United States
Cancer Therapy & Research Center
🇺🇸San Antonio, Texas, United States
Complejo Hospitalario Regional Reina Sofía
🇪🇸Córdoba, Spain
Hospital Universitari Vall D'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Hospital Universitario Madrid Sanchinarro
🇪🇸Madrid, Spain
Hospital Universitario Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Spain
Complejo Hospitalario de Especialidades Virgen de La Victoria
🇪🇸Málaga, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Complexo Hospitalario Universitario de Santiago
🇪🇸Santiago De Compostela, Spain
Hospital Ramón Y Cajal
🇪🇸Madrid, Spain