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

PharmaMar39 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Solid Tumors

Interventions

lurbinectedin (PM01183)DRUG

Eligibility

Sex: ALLMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (16)

Sarcoma Oncology Research Center

Santa Monica, California, United States

University of Colorado Cancer Center

Aurora, Colorado, United States

Outcomes

Primary Outcomes

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

Time frame: 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 Outcomes

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.

Time frame: 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)

Time frame: 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)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.