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

Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02451007
• Other study ID #: PM1183-B-005-14-QT
• Status: Completed
• Phase: Phase 2
• Start date: August 12, 2015
• Est. completion date: August 19, 2016

Study information

• Verified date: November 2019
• Source: PharmaMar
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: August 19, 2016
• Est. primary completion date: August 19, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

Intervention

Drug:
• lurbinectedin (PM01183)

Locations

Country	Name	City	State
Spain	Hospital Universitari Vall D'Hebron	Barcelona
Spain	Complejo Hospitalario Regional Reina Sofía	Córdoba
Spain	Hospital Ramón Y Cajal	Madrid
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	Complexo Hospitalario Universitario de Santiago	Santiago De Compostela
Spain	Hospital Universitari I Politècnic La Fe	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Dana Farber Cancer lnstitute	Boston	Massachusetts
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Cancer Therapy & Research Center	San Antonio	Texas
United States	Sarcoma Oncology Research Center	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
PharmaMar

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in QTcF (QT Corrected According to Fridericia's Formula)	?QTCF (Change in QTcF); EOI (end of infusion); LSM (Least Square Means); PK (Pharmacokinetic(s)).; On Day 1 (D1) of Cycle 1 (C1), LSM ?QTcF 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	Relationship Between ?QTcF and Time-matched Lurbinectedin Plasma Concentrations (Plasma Concentration)	?QTcF (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 ?QTcF and Predicted ?QTcF and 90% CI at mean lurbinectedin Cmax.	Through study completion, each patient had to be followed for 2 cycles (1 cycle =3 weeks)
Secondary	Relationship Between ?QTcF and Time-matched Lurbinectedin Plasma Concentrations (Predicted ?QTcF)	?QTcF (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 ?QTcF and Predicted ?QTcF and 90% CI at mean lurbinectedin Cmax.	Through study completion, each patient had to be followed for 2 cycles (1 cycle =3 weeks)
Secondary	Relationship Between ?QTcF and Time-matched Lurbinectedin Plasma Concentrations (Intercept)	?QTcF (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 ?QTcF and Predicted ?QTcF and 90% CI at mean lurbinectedin Cmax.	Through study completion, each patient had to be followed for 2 cycles (1 cycle =3 weeks)