Solid TumorsPhase 2NCT02451007

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

A Phase 2 study testing lurbinectedin (PM01183) in people with Solid Tumors, run by PharmaMar at 16 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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. Read more about this study

Who is it for?: Ages Up to 65 years
Conditions the study is for: Solid Tumors
What is being tested?: lurbinectedin (PM01183)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 39 participants
Where: 16 sitesin 2 countries
Study dates: 12 Aug 2015to 19 Aug 2016
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 65 years
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

16 sites in 2 countries.

Country

City, postcode or hospital

16 sites in 2 countries

Spain11 sites

Hospital Universitari Vall D'Hebron
Barcelona, 08035
Complejo Hospitalario Regional Reina Sofía
Córdoba, 14004
Hospital Universitario 12 de Octubre
Madrid, 280035
Hospital Ramón Y Cajal
Madrid, 28034
Hospital Universitario Fundación Jiménez Díaz
Madrid, 28040
Hospital Universitario Madrid Sanchinarro
Madrid, 28050
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, 28222
Complejo Hospitalario de Especialidades Virgen de La Victoria
Málaga, 29010
Complexo Hospitalario Universitario de Santiago
Santiago de Compostela, 15706
Hospital Universitari I Politècnic La Fe
Valencia, 46026
Hospital Universitario Miguel Servet
Zaragoza, 50009

Other trials in Spain

United States5 sites

University of Colorado Cancer Center
Aurora, Colorado, 80045
Dana Farber Cancer lnstitute
Boston, Massachusetts, 02215
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Cancer Therapy & Research Center
San Antonio, Texas, 78229
Sarcoma Oncology Research Center
Santa Monica, California, 90403

Other trials in United States

About this study

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

Conditions: Solid Tumors
Being tested: lurbinectedin (PM01183)

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

lurbinectedin (PM01183)Drug

Study groups in NCT02451007
Study group	Role	What they receive
A (lurbinectedin)	Experimental	lurbinectedin (PM01183) 4 mg vials of powder for concentrate for solution for infusion Receives: Drug: lurbinectedin (PM01183)

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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 (3)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Aug 201519 Aug 2016

First posted21 May 2015 (estimated)
Study start12 Aug 2015
Primary completion19 Aug 2016
Study completion19 Aug 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Solid TumorsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 39 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02451007
Sponsor's protocol ID: PM1183-B-005-14-QT
Status last verified: Nov 2019
First submitted: 12 May 2015
Last updated: 19 Nov 2019
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm

All Solid Tumors trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Evaluation of the Effect of Lurbinectedin (PM01183) on Cardiac Repolarization (QTc Duration) in Patients With Selected Solid Tumors
ClinicalTrials.gov ID: NCT02451007
Acronym / sponsor ID: PM1183-B-005-14-QT
Conditions: Solid Tumors
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 39 participants (actual)
Lead sponsor: PharmaMarIndustry (pharma, biotech, devices)
Study start: 12 Aug 2015 (actual)
Primary completion: 19 Aug 2016 (actual)
Study completion: 19 Aug 2016 (actual)
First posted: 21 May 2015 (estimated)
Results: Posted 18 Feb 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
A (lurbinectedin)	Experimental	Drug: lurbinectedin (PM01183)lurbinectedin (PM01183) 4 mg vials of powder for concentrate for solution for infusion

Who may qualify

Ages: Up to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
lurbinectedin (PM01183)	Drug	A (lurbinectedin)

Primary outcome

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

3 secondary outcomes

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

Results and safety

Results posted to the registry on 18 Feb 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group A - Lurbinectedin (PM01183)	39	32

Primary outcome: 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.. Least squares mean (90% Confidence Interval). Unit: ms (Milliseconds)

Measure	Group A - Lurbinectedin (PM01183) n = 39
Cycle 1 - 5 min before EOI	3.32 (1.12 to 5.51)
Cycle 1 - 30 min after EOI	1.76 (-0.41 to 3.93)
Cycle 1 - 1 hour after EOI	1.84 (-1.02 to 4.69)
Cycle 1 - 3 hour after EOI	1.32 (-1.40 to 4.05)
Cycle 1 - 24 hour after EOI	-8.24 (-11.2 to -5.26)
Cycle 1 - 72 hour after EOI	-12.4 (-15.4 to -9.39)
Cycle 1 - 168 hour after EOI	-5.20 (-7.98 to -2.41)
Cycle 2 - Before start of infusion	-0.46 (-3.27 to 2.35)

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Through study completion, each patient had to be followed for 2 cycles (1 cycle =3 weeks). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group A - Lurbinectedin (PM01183)	9 of 39 (23.1%)	35 of 39 (89.7%)	13 of 39

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Solid Tumors

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

16 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing lurbinectedin (PM01183) in people with Solid Tumors, run by PharmaMar at 16 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in Spain, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02451007.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2019.