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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A (lurbinectedin) | Experimental | lurbinectedin (PM01183) 4 mg vials of powder for concentrate for solution for infusion |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| lurbinectedin (PM01183) | Drug |
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| 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. |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sarcoma Oncology Research Center | Santa Monica | California | 90403 | United States | ||
| University of Colorado Cancer Center |
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This study was nested into a multicenter clinical trial with a competitive recruitment. From August 2015 to June 2016, a total of 39 evaluable patients at 12 sites in USA and Spain were included in this QT evaluation study with baseline and one or more postbaseline Electrocardiogram (ECG) assessments available.
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| ID | Title | Description |
|---|---|---|
| FG000 | Group A - Lurbinectedin (PM01183) | lurbinectedin (PM01183) is presented as a lyophilized powder for concentrate for solution for infusion with strength of 4 mg / vial. Lurbinectedin was administered at a dose of 3.2 mg/m² given as a 1-hour i.v. every three weeks (q3wk) (three weeks = one treatment cycle). QTc interval duration was assessed when the patient was treated with lurbinectedin for the first time. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| 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) |
| Aurora |
| Colorado |
| 80045 |
| United States |
| Dana Farber Cancer lnstitute | Boston | Massachusetts | 02215 | United States |
| The University of Texas MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| Cancer Therapy & Research Center | San Antonio | Texas | 78229 | United States |
| Hospital Universitari Vall D'Hebron | Barcelona | 08035 | Spain |
| Complejo Hospitalario Regional Reina SofÃa | Córdoba | 14004 | Spain |
| Hospital Universitario 12 de Octubre | Madrid | 280035 | Spain |
| Hospital Ramón Y Cajal | Madrid | 28034 | Spain |
| Hospital Universitario Fundación Jiménez DÃaz | Madrid | 28040 | Spain |
| Hospital Universitario Madrid Sanchinarro | Madrid | 28050 | Spain |
| Hospital Universitario Puerta de Hierro Majadahonda | Majadahonda | 28222 | Spain |
| Complejo Hospitalario de Especialidades Virgen de La Victoria | Málaga | 29010 | Spain |
| Complexo Hospitalario Universitario de Santiago | Santiago de Compostela | 15706 | Spain |
| Hospital Universitari I Politècnic La Fe | Valencia | 46026 | Spain |
| Hospital Universitario Miguel Servet | Zaragoza | 50009 | Spain |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Group A - Lurbinectedin (PM01183) | lurbinectedin (PM01183) is presented as a lyophilized powder for concentrate for solution for infusion with strength of 4 mg / vial. Lurbinectedin was administered at a dose of 3.2 mg/m² given as a 1-hour i.v. every three weeks (q3wk) (three weeks = one treatment cycle). QTc interval duration was assessed when the patient was treated with lurbinectedin for the first time. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | Posted | Least Squares Mean | 90% Confidence Interval | ms (Milliseconds) | 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. |
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| Secondary | 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. | Posted | Mean | 90% Confidence Interval | Microgram/milliliter (μg/mL) | Through study completion, each patient had to be followed for 2 cycles (1 cycle =3 weeks) |
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| Secondary | 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. | Posted | Mean | 90% Confidence Interval | Milliseconds (ms) | Through study completion, each patient had to be followed for 2 cycles (1 cycle =3 weeks) |
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| Secondary | 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. | Posted | Number | 90% Confidence Interval | Unitless | Through study completion, each patient had to be followed for 2 cycles (1 cycle =3 weeks) |
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Through study completion, each patient had to be followed for 2 cycles (1 cycle =3 weeks)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group A - Lurbinectedin (PM01183) | lurbinectedin (PM01183) is presented as a lyophilized powder for concentrate for solution for infusion with strength of 4 mg / vial. Lurbinectedin was administered at a dose of 3.2 mg/m² given as a 1-hour i.v. every three weeks (q3wk) (three weeks = one treatment cycle). | 13 | 39 | 9 | 39 | 35 | 39 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blood calcium decreased | Investigations | MedDRA (16.0) | Systematic Assessment |
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| Blood phosphorus decreased | Investigations | MedDRA (16.0) | Systematic Assessment |
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| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
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| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
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| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (16.0) | Systematic Assessment |
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| Facial paralysis | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
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| General physical health deterioration | General disorders | MedDRA (16.0) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
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| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
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| Cholangitis | Hepatobiliary disorders | MedDRA (16.0) | Systematic Assessment |
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| Device related infection | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
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| Skin infection | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (16.0) | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA (16.0) | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (16.0) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (16.0) | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA (16.0) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Development Department of PharmaMar's Oncology Business Unit | Pharma Mar, S.A. | +34 91 846 60 00 | clinicaltrials@pharmamar.com |
| ID | Term |
|---|---|
| C568606 | PM 01183 |
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| Cycle 1 - 3 hour after EOI |
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| Cycle 1 - 24 hour after EOI |
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| Cycle 1 - 72 hour after EOI |
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| Cycle 1 - 168 hour after EOI |
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| Cycle 2 - Before start of infusion |
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| Cycle 2 - 5 min before EOI |
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| Cycle 2 - 30 min after EOI |
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| Cycle 2 - 1 hour after EOI |
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| Cycle 2 - 3 hour after EOI |
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| Cycle 2 - 168 hour after EOI |
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