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

Study Overview
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Brief Summary
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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.

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

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: lurbinectedin (PM01183)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A (lurbinectedin)<br>lurbinectedin (PM01183) 4 mg vials of powder for concentrate for solution for infusion | Drug: lurbinectedin (PM01183)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in QTcF (QT Corrected According to Fridericia's Formula) | 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 | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship Between ΔQTcF and Time-matched Lurbinectedin Plasma Concentrations (Plasma Concentration) | 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. | Through study completion, each patient had to be followed for 2 cycles (1 cycle =3 weeks) | 
| Relationship Between ΔQTcF and Time-matched Lurbinectedin Plasma Concentrations (Predicted ΔQTcF) | 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. | Through study completion, each patient had to be followed for 2 cycles (1 cycle =3 weeks) | 
| Relationship Between ΔQTcF and Time-matched Lurbinectedin Plasma Concentrations (Intercept) | 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. | Through study completion, each patient had to be followed for 2 cycles (1 cycle =3 weeks) |