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

November 6, 2019 updated by: PharmaMar

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

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 Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

39

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Córdoba, Spain, 14004
        • Complejo Hospitalario Regional Reina Sofía
      • Madrid, Spain, 28040
        • Hospital Universitario Fundacion Jimenez Diaz
      • Madrid, Spain, 28034
        • Hospital Ramón y Cajal
      • Madrid, Spain, 28050
        • Hospital Universitario Madrid Sanchinarro
      • Madrid, Spain, 280035
        • Hospital Universitario 12 de Octubre
      • Majadahonda, Spain, 28222
        • Hospital Universitario Puerta de Hierro Majadahonda
      • Málaga, Spain, 29010
        • Complejo Hospitalario de Especialidades Virgen de la Victoria
      • Santiago De Compostela, Spain, 15706
        • Complexo Hospitalario Universitario De Santiago
      • Valencia, Spain, 46026
        • Hospital Universitari I Politecnic La Fe
      • Zaragoza, Spain, 50009
        • Hospital Universitario Miguel Servet
  • United States
    • California
      • Santa Monica, California, United States, 90403
        • Sarcoma Oncology Research Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer lnstitute
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center
      • San Antonio, Texas, United States, 78229
        • Cancer Therapy & Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 65 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: A (lurbinectedin)
lurbinectedin (PM01183) 4 mg vials of powder for concentrate for solution for infusion
Drug: lurbinectedin (PM01183)

What is the study measuring?

Primary Outcome Measures

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

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)
Time Frame: 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.
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)

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)
Time Frame: 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.
Through study completion, each patient had to be followed for 2 cycles (1 cycle =3 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

PharmaMar

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

August 12, 2015

Primary Completion (ACTUAL)

August 19, 2016

Study Completion (ACTUAL)

August 19, 2016

Study Registration Dates

First Submitted

May 12, 2015

First Submitted That Met QC Criteria

May 18, 2015

First Posted (ESTIMATE)

May 21, 2015

Study Record Updates

Last Update Posted (ACTUAL)

November 19, 2019

Last Update Submitted That Met QC Criteria

November 6, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PM1183-B-005-14-QT

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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