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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-002610-31 | EudraCT Number | ||
| U1111-1201-10111 | Registry Identifier | WHO |
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The purpose of this study is to characterize the effects of 25 and 50 milligram per square meter (mg/m^2) pevonedistat on the Fridericia corrected QT interval (QTcF) of the electrocardiogram (ECG).
The drug being tested in this study is called pevonedistat. Pevonedistat in combination with standard of care will be used to treat participants who have advanced solid tumors. This study will assess the effects of pevonedistat on the QTc interval in participants with advanced solid tumors.
The study will enroll approximately 45 participants. The study will be conducted in two Parts: Part A and Part B. Part A will have a 2-way crossover design and will involve the collection of triplicate ECGs. In Part A, participants will be randomly assigned to one of the two treatment groups as follow:
Eligible participants from Part A will continue treatment in optional Part B with pevonedistat in combination with SoC, docetaxel or carboplatin plus paclitaxel. The investigator will decide which pevonedistat combination a participant will receive.
This multi-center trial will be conducted in the United States. The overall time to participate in this study is 9.6 months. Participants will make a final visit to the clinic 30 days after receiving their last dose of study drug for a follow-up assessment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: Pevonedistat 25 mg/m^2 + Pevonedistat 50 mg/m^2 | Experimental | Pevonedistat 25 mg/m^2, infusion, intravenously, once on Day 1 of Cycle 1, followed by pevonedistat 50 mg/m^2, infusion, intravenously, once on Day 8 of Cycle 1. |
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| Part A: Pevonedistat 50 mg/m^2 + Pevonedistat 25 mg/m^2 | Experimental | Pevonedistat 50 mg/m^2, infusion, intravenously, once on Day 1 of Cycle 1, followed by pevonedistat 25 mg/m^2, infusion, intravenously, once on Day 8 of Cycle 1. |
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| Part B: Pevonedistat | Experimental | Pevonedistat 25 mg/m^2 in combination with docetaxel 75 mg/m^2 or pevonedistat 20 mg/m^2 in combination with carboplatin plus paclitaxel 175 mg/m^2, infusion, intravenously, once on Day 1 in each 21-day treatment cycle followed by pevonedistat 25 mg/m^2 or 20 mg/m^2 infusion, intravenously, once on Days 3 and 5 in each 21-day treatment cycle for up to 12 cycles or symptomatic deterioration or PD, treatment is discontinued for another reason, or until the study is stopped. The combination and dose of pevonedistat will be based on investigator discretion. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pevonedistat | Drug | Pevonedistat intravenous infusion. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Change From Time-matched Baseline in Fridericia-corrected QT Interval (QTcF) After Pevonedistat Administration | Change from time-matched baseline in QTcF was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m^2 or 50 mg/m^2 on Day 1 while others received treatment on Day 8. Data is reported at pre-dose and at multiple timepoints (1, 2, 3, 4, 6, 9, 11 and 24 hours) postdose up to Day 8 in Part A. Analysis of variance (ANOVA) was used for the analysis. | Baseline up to Day 8 |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Change From Time-matched Baseline in Individual Corrected QT Interval (QTcI) After Pevonedistat Administration | Change from time-matched baseline in QTcI was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m^2 or 50 mg/m^2 on Day 1 while others received treatment on Day 8. ANOVA was used for the analysis. |
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Inclusion Criteria:
Exclusion Criteria:
Entry Criteria for Continuation to Optional Part B:
After completing Part A of the study, participants may choose to enter the optional Part B of the study. To be eligible for the optional Part B, participants must have completed Part A and be reassessed to determine if they meet the entry criteria for optional Part B. Only participants who meet the following criteria may enter into Part B:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Millennium Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sarcoma Oncology Center | Santa Monica | California | 90403 | United States | ||
| Moffitt Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36382849 | Derived | Zhou X, Richardson DL, Dowlati A, Goel S, Sahebjam S, Strauss J, Chawla S, Wang D, Mould DR, Samnotra V, Faller DV, Venkatakrishnan K, Gupta N. Effect of Pevonedistat, an Investigational NEDD8-Activating Enzyme Inhibitor, on the QTc Interval in Patients With Advanced Solid Tumors. Clin Pharmacol Drug Dev. 2023 Mar;12(3):257-266. doi: 10.1002/cpdd.1194. Epub 2022 Nov 16. |
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Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Participants with histologically or cytologically confirmed metastatic or locally advanced solid tumor were enrolled in this 2-part study to receive intravenous infusion of pevonedistat in Part A and pevonedistat in combination with chemotherapy agents in Part B (optional part). After completion of Part A, participants had an opportunity to continue into optional Part B.
A total of 44 participants took part in this study at 8 investigative sites in the United States from 15 November 2017 to 21 June 2021.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A: Pevonedistat 25 mg/m^2 + Pevonedistat 50 mg/m^2 | Pevonedistat 25 mg/m^2, infusion, intravenously (IV), once on Day 1, followed by pevonedistat 50 mg/m^2, infusion, IV, once on Day 8 in Part A. |
| FG001 | Part A: Pevonedistat 50 mg/m^2 + Pevonedistat 25 mg/m^2 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Part A |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 26, 2017 | Jun 13, 2022 |
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| Docetaxel | Drug | Docetaxel intravenous infusion. |
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| Carboplatin | Drug | Carboplatin intravenous infusion. |
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| Paclitaxel | Drug | Paclitaxel intravenous infusion. |
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| Predose, and at multiple time points up to 24 hours post dose on Day 1 or Day 8 in Part A |
| Part A: Change From Time-matched Baseline in QRS After Pevonedistat Administration | Change from time-matched baseline in QRS was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m^2 or 50 mg/m^2 on Day 1 while others received treatment on Day 8. ANOVA was used for the analysis. | Predose, and at multiple time points post dose up to 24 hours on Day 1 or Day 8 in Part A |
| Part A: Change From Time-matched Baseline in PR After Pevonedistat Administration | Change from time-matched baseline in PR was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m^2 or 50 mg/m^2 on Day 1 while others received treatment on Day 8. ANOVA was used for the analysis. | Predose, and at multiple time points post dose up to 24 hours on Day 1 or Day 8 in Part A |
| Part A: Change From Time-matched Baseline in Heart Rate (HR) After Pevonedistat Administration | Change from time-matched baseline in HR was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m^2 or 50 mg/m^2 on Day 1 while others received treatment on Day 8. ANOVA was used for the analysis. | Predose, and at multiple time points post dose up to 24 hours on Day 1 or Day 8 in Part A |
| Part A: Cmax: Maximum Observed Plasma Concentration for Pevonedistat | Days 1 or 8 predose and at multiple time points (up to 24 hours) post dose in Part A |
| Part A: AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Postdose for Pevonedistat | Days 1 or 8 predose and at multiple time points (up to 24 hours) post dose in Part A |
| Part A: Terminal Phase Elimination Half-life (t1/2) for Pevonedistat | Days 1 or 8 predose and at multiple time points (up to 24 hours) post dose in Part A |
| Part B: Overall Response Rate (ORR) | Percentage of participants who achieve an overall response per investigator's assessment at end of treatment,according to Response Evaluation Criteria in Solid Tumor(RECIST),version 1.1 guideline. Complete response(CR):Disappearance of all target lesions.Any pathological lymph nodes(whether target and non target)must have reduction in short axis to <10 millimeter(mm).Partial Response(PR):atleast 30% decrease in sum of diameter of target lesions,taking as reference baseline sum of diameter.Stable Disease(SD):Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression(PD),taking as reference smallest sum of diameter; PD:atleast 20% increase in sum of diameter of target lesions,taking as reference,smallest sum on study(this includes baseline sum if that is smallest on study).In addition to relative increase of 20%,sum must also demonstrate an absolute increase of atleast 5 mm.Appearance of 1 or more new lesions is also considered progression. | Up to Cycle 45 (end of treatment) (Cycle length=21 days) |
| Tampa |
| Florida |
| 33612 |
| United States |
| Henry Ford Hospital | Detroit | Michigan | 48202 | United States |
| Montefiore Medical Center | The Bronx | New York | 10467 | United States |
| Case Western Reserve University | Cleveland | Ohio | 44106 | United States |
| University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | 23801 | United States |
| Mary Crowley Medical Research | Dallas | Texas | 75231 | United States |
| Virginia Cancer Specialists | Fairfax | Virginia | 22031 | United States |
Pevonedistat 50 mg/m^2, infusion, IV, once on Day 1, followed by pevonedistat 25 mg/m^2, infusion, IV, once on Day 8 in Part A. |
| FG002 | Part B: Pevonedistat 25 mg/m^2 + Docetaxel | Pevonedistat 25 mg/m^2 in combination with docetaxel 75 mg/m^2, infusion, IV, once on Day 1 followed by pevonedistat 25 mg/m^2 IV, once on Days 3 and 5 in each 21-day treatment cycle for up to Cycle 45 or symptomatic deterioration or progressive disease (PD), or until treatment is discontinued for another reason. Pevonedistat was administered after the docetaxel chemotherapy. Participants who completed Part A and provided consent for Part B continued treatment in Part B. |
| FG003 | Part B: Pevonedistat 20 mg/m^2 + Carboplatin + Paclitaxel | Pevonedistat 20 mg/m^2 in combination with carboplatin area under the plasma concentration (AUC) at the dose of 5 milligram per minute per milliliter (mg/min/mL), infusion, IV and paclitaxel 175 mg/m^2, infusion, IV, once on Day 1 in each 21-day treatment cycle followed by pevonedistat 20 mg/m^2 IV, once on Days 3 and 5 in each 21-day treatment cycle for up to 20 cycles or symptomatic deterioration or PD, or until treatment is discontinued for another reason. Pevonedistat was administered after the paclitaxel and carboplatin chemotherapy. Participants who completed Part A and provided consent for Part B continued treatment in Part B. |
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| NOT COMPLETED |
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| Part B |
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Randomized Population included all participants who had a randomization date and had been randomized to a treatment sequence.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A: Pevonedistat 25 mg/m^2 + Pevonedistat 50 mg/m^2 | Pevonedistat 25 mg/m^2, infusion, intravenously (IV), once on Day 1, followed by pevonedistat 50 mg/m^2, infusion, IV, once on Day 8 in Part A. |
| BG001 | Part A: Pevonedistat 50 mg/m^2 + Pevonedistat 25 mg/m^2 | Pevonedistat 50 mg/m^2, infusion, IV, once on Day 1, followed by pevonedistat 25 mg/m^2, infusion, IV, once on Day 8 in Part A. |
| BG002 | Total | Total of all reporting groups |
| 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, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | 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 | Part A: Change From Time-matched Baseline in Fridericia-corrected QT Interval (QTcF) After Pevonedistat Administration | Change from time-matched baseline in QTcF was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m^2 or 50 mg/m^2 on Day 1 while others received treatment on Day 8. Data is reported at pre-dose and at multiple timepoints (1, 2, 3, 4, 6, 9, 11 and 24 hours) postdose up to Day 8 in Part A. Analysis of variance (ANOVA) was used for the analysis. | QT Population included all participants who received the protocol-specified pevonedistat dosing and had sufficient electrocardiogram (ECG) assessments in the Baseline period (Day -1) and at least one period of assessment of effect of pevonedistat (Day 1 or Day 8) to permit reliable analysis. Overall number analyzed are the number of participants with evaluable data for analyses by dose. Number analyzed is the number of participants with data available for analysis at the given time point. | Posted | Least Squares Mean | 90% Confidence Interval | milliseconds | Baseline up to Day 8 |
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| Secondary | Part A: Change From Time-matched Baseline in Individual Corrected QT Interval (QTcI) After Pevonedistat Administration | Change from time-matched baseline in QTcI was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m^2 or 50 mg/m^2 on Day 1 while others received treatment on Day 8. ANOVA was used for the analysis. | QT Population included all participants who received the protocol-specified pevonedistat dosing and had sufficient ECG assessments in the Baseline period (Day -1) and at least one period of assessment of effect of pevonedistat (Day 1 or Day 8) to permit reliable analysis. Overall number analyzed are the number of participants with evaluable data for analyses by dose. Number analyzed is the number of participants with data available for analysis at the given time point. | Posted | Least Squares Mean | 90% Confidence Interval | milliseconds | Predose, and at multiple time points up to 24 hours post dose on Day 1 or Day 8 in Part A |
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| Secondary | Part A: Change From Time-matched Baseline in QRS After Pevonedistat Administration | Change from time-matched baseline in QRS was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m^2 or 50 mg/m^2 on Day 1 while others received treatment on Day 8. ANOVA was used for the analysis. | QT Population included all participants who received the protocol-specified pevonedistat dosing and had sufficient ECG assessments in the Baseline period (Day -1) and at least one period of assessment of effect of pevonedistat (Day 1 or Day 8) to permit reliable analysis. Overall number analyzed are the number of participants with evaluable data for analyses by dose. Number analyzed is the number of participants with data available for analysis at the given time point. | Posted | Least Squares Mean | 90% Confidence Interval | milliseconds | Predose, and at multiple time points post dose up to 24 hours on Day 1 or Day 8 in Part A |
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| Secondary | Part A: Change From Time-matched Baseline in PR After Pevonedistat Administration | Change from time-matched baseline in PR was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m^2 or 50 mg/m^2 on Day 1 while others received treatment on Day 8. ANOVA was used for the analysis. | QT Population included all participants who received the protocol-specified pevonedistat dosing and had sufficient ECG assessments in the Baseline period (Day -1) and at least one period of assessment of effect of pevonedistat (Day 1 or Day 8) to permit reliable analysis. Overall number analyzed are the number of participants with evaluable data for analyses by dose. Number analyzed is the number of participants with data available for analysis at the given time point. | Posted | Least Squares Mean | 90% Confidence Interval | milliseconds | Predose, and at multiple time points post dose up to 24 hours on Day 1 or Day 8 in Part A |
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| Secondary | Part A: Change From Time-matched Baseline in Heart Rate (HR) After Pevonedistat Administration | Change from time-matched baseline in HR was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m^2 or 50 mg/m^2 on Day 1 while others received treatment on Day 8. ANOVA was used for the analysis. | QT Population included all participants who received the protocol-specified pevonedistat dosing and had sufficient ECG assessments in the Baseline period (Day -1) and at least one period of assessment of effect of pevonedistat (Day 1 or Day 8) to permit reliable analysis. Overall number analyzed are the number of participants with evaluable data for analyses by dose. Number analyzed is the number of participants with data available for analysis at the given time point. | Posted | Least Squares Mean | 90% Confidence Interval | beats per minute (bpm) | Predose, and at multiple time points post dose up to 24 hours on Day 1 or Day 8 in Part A |
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| Secondary | Part A: Cmax: Maximum Observed Plasma Concentration for Pevonedistat | Pharmacokinetic (PK) Population included all participants who received the protocol-specified pevonedistat dosing during Part A and had sufficient PK assessments to permit reliable estimation of PK parameters. Overall number analyzed are the number of participants with evaluable data for analyses by dose. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | Days 1 or 8 predose and at multiple time points (up to 24 hours) post dose in Part A |
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| Secondary | Part A: AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Postdose for Pevonedistat | PK Population included all participants who received the protocol-specified pevonedistat dosing during Part A and had sufficient PK assessments to permit reliable estimation of PK parameters. Overall number analyzed are the number of participants with evaluable data for analyses by dose. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram per milliliter (h*ng/mL) | Days 1 or 8 predose and at multiple time points (up to 24 hours) post dose in Part A |
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| Secondary | Part A: Terminal Phase Elimination Half-life (t1/2) for Pevonedistat | PK Population included all participants who received the protocol-specified pevonedistat dosing during Part A and had sufficient PK assessments to permit reliable estimation of PK parameters. Overall number analyzed are the number of participants with evaluable data for analyses. | Posted | Mean | Standard Deviation | hours (h) | Days 1 or 8 predose and at multiple time points (up to 24 hours) post dose in Part A |
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| Secondary | Part B: Overall Response Rate (ORR) | Percentage of participants who achieve an overall response per investigator's assessment at end of treatment,according to Response Evaluation Criteria in Solid Tumor(RECIST),version 1.1 guideline. Complete response(CR):Disappearance of all target lesions.Any pathological lymph nodes(whether target and non target)must have reduction in short axis to <10 millimeter(mm).Partial Response(PR):atleast 30% decrease in sum of diameter of target lesions,taking as reference baseline sum of diameter.Stable Disease(SD):Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression(PD),taking as reference smallest sum of diameter; PD:atleast 20% increase in sum of diameter of target lesions,taking as reference,smallest sum on study(this includes baseline sum if that is smallest on study).In addition to relative increase of 20%,sum must also demonstrate an absolute increase of atleast 5 mm.Appearance of 1 or more new lesions is also considered progression. | Disease-response population included participants who received at least 1 dose of study drug in Part B, had measurable disease as entry criteria for Part B, and had at least 1 postbaseline disease assessment. | Posted | Number | percentage of participants | Up to Cycle 45 (end of treatment) (Cycle length=21 days) |
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From first dose of study drug up to approximately 188 weeks (up to approximately 3.6 years)
Safety Population for Part A included all participants who received at least 1 dose of pevonedistat during Part A. Safety population for Part B included all participants who continued to Part B and received at least 1 dose of study drugs during Part B. For Part A, MedDRA Version 22.0 was used and for Part B MedDRA version 24.0 was used.
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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 | Part A: Pevonedistat 25 mg/m^2 + Pevonedistat 50 mg/m^2 | Pevonedistat 25 mg/m^2, infusion, intravenously (IV), once on Day 1, followed by pevonedistat 50 mg/m^2, infusion, IV, once on Day 8 in Part A. | 2 | 22 | 3 | 22 | 13 | 22 |
| EG001 | Part A: Pevonedistat 50 mg/m^2 + Pevonedistat 25 mg/m^2 | Pevonedistat 50 mg/m^2, infusion, IV, once on Day 1, followed by pevonedistat 25 mg/m^2, infusion, IV, once on Day 8 in Part A. | 4 | 22 | 5 | 22 | 17 | 22 |
| EG002 | Part B: Pevonedistat 25 mg/m^2 + Docetaxel | Pevonedistat 25 mg/m^2 in combination with docetaxel 75 mg/m^2, infusion, IV, once on Day 1 followed by pevonedistat 25 mg/m^2 IV, once on Days 3 and 5 in each 21-day treatment cycle for up to Cycle 45 or symptomatic deterioration or progressive disease (PD), or until treatment is discontinued for another reason. Pevonedistat was administered after the docetaxel chemotherapy. Participants who completed Part A and provided consent for Part B continued treatment in Part B. | 2 | 23 | 13 | 23 | 23 | 23 |
| EG003 | Part B: Pevonedistat 20 mg/m^2 + Carboplatin + Paclitaxel | Pevonedistat 20 mg/m^2 in combination with carboplatin area under the plasma concentration (AUC) at the dose of 5 mg/min/mL, infusion, IV and paclitaxel 175 mg/m^2, infusion, IV, once on Day 1 in each 21-day treatment cycle followed by pevonedistat 20 mg/m^2 IV, once on Days 3 and 5 in each 21-day treatment cycle for up to 20 cycles or symptomatic deterioration or PD, or until treatment is discontinued for another reason. Pevonedistat was administered after the paclitaxel and carboplatin chemotherapy. Participants who completed Part A and provided consent for Part B continued treatment in Part B. | 0 | 12 | 5 | 12 | 12 | 12 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA22.0 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA22.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA22.0 | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA22.0 | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA22.0 | Systematic Assessment |
| |
| Fallopian tube cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA22.0 | Systematic Assessment |
| |
| Pancreatic carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA22.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA22.0 | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA22.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA22.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA22.0 | Systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA22.0 | Systematic Assessment |
| |
| Disseminated varicella zoster virus infection | Infections and infestations | MedDRA22.0 | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA22.0 | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA22.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA22.0 | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | MedDRA22.0 | Systematic Assessment |
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| Ileus | Gastrointestinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA22.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA22.0 | Systematic Assessment |
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| Malaise | General disorders | MedDRA22.0 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA22.0 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA22.0 | Systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA22.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA22.0 | Systematic Assessment |
| |
| Hypernatraemia | Metabolism and nutrition disorders | MedDRA22.0 | Systematic Assessment |
| |
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA22.0 | Systematic Assessment |
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| Mental status changes | Psychiatric disorders | MedDRA22.0 | Systematic Assessment |
| |
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA22.0 | Systematic Assessment | The number of participants exposed to this adverse event is based on the female population. |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Aspartate aminotransferase increased | Investigations | MedDRA22.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA22.0 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA22.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA22.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA22.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA22.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA22.0 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA22.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA22.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA22.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA22.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA22.0 | Systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA22.0 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA22.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA22.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA22.0 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA22.0 | Systematic Assessment |
| |
| Localised oedema | General disorders | MedDRA22.0 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA22.0 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA22.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Glossodynia | Gastrointestinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Colitis ischaemic | Gastrointestinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Peripheral motor neuropathy | Nervous system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Amnesia | Nervous system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Dizziness postural | Nervous system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Drooling | Nervous system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Dysarthria | Nervous system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Facial paralysis | Nervous system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Taste disorder | Nervous system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA22.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA22.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA22.0 | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA22.0 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA22.0 | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA22.0 | Systematic Assessment |
| |
| Urine output decreased | Investigations | MedDRA22.0 | Systematic Assessment |
| |
| Vitamin D decreased | Investigations | 22.0 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA22.0 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Tachypnoea | Respiratory, thoracic and mediastinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA22.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA22.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA22.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA22.0 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA22.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA22.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA22.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA22.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA22.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA22.0 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA22.0 | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA22.0 | Systematic Assessment |
| |
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA22.0 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA22.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA22.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA22.0 | Systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA22.0 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA22.0 | Systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA22.0 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA22.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA22.0 | Systematic Assessment |
| |
| Dermatitis atopic | Skin and subcutaneous tissue disorders | MedDRA22.0 | Systematic Assessment |
| |
| Macule | Skin and subcutaneous tissue disorders | MedDRA22.0 | Systematic Assessment |
| |
| Pain of skin | Skin and subcutaneous tissue disorders | MedDRA22.0 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA22.0 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA22.0 | Systematic Assessment |
| |
| Atrioventricular block first degree | Cardiac disorders | MedDRA22.0 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA22.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA22.0 | Systematic Assessment |
| |
| Incision site oedema | Injury, poisoning and procedural complications | MedDRA22.0 | Systematic Assessment |
| |
| Overdose | Injury, poisoning and procedural complications | MedDRA22.0 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA22.0 | Systematic Assessment |
| |
| Micturition urgency | Renal and urinary disorders | MedDRA22.0 | Systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA22.0 | Systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MedDRA22.0 | Systematic Assessment |
| |
| Seasonal allergy | Immune system disorders | MedDRA22.0 | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA22.0 | Systematic Assessment |
| |
| Portal vein thrombosis | Hepatobiliary disorders | MedDRA22.0 | Systematic Assessment |
| |
| Sleep disorder | Psychiatric disorders | MedDRA22.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA22.0 | Systematic Assessment |
|
In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Takeda | +1-877-825-3327 | TrialDisclosures@takeda.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 11, 2019 | Jun 13, 2022 | SAP_001.pdf |
| ID | Term |
|---|---|
| C539933 | pevonedistat |
| D000077143 | Docetaxel |
| D016190 | Carboplatin |
| D017239 | Paclitaxel |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D056831 | Coordination Complexes |
Not provided
Not provided
| Withdrawal by Subject |
|
| Death |
|
| Clinical Progression |
|
| Symptomatic Deterioration |
|
| Symptomatic Deterioration, Participant Placed on Hospice |
|
| Progressive Disease |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| 1 Hour Postdose |
|
|
| 2 Hours Postdose |
|
|
| 3 Hours Postdose |
|
|
| 4 Hours Postdose |
|
|
| 6 Hours Postdose |
|
|
| 9 Hours Postdose |
|
|
| 11 Hours Postdose |
|
|
| 24 Hours Postdose |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Units | Counts |
|---|
| Participants |
|
|
| Units | Counts |
|---|
| Participants |
|
|
| Units | Counts |
|---|
| Participants |
|
|
|
|
|
| OG001 | Part B: Pevonedistat 20 mg/m^2 + Carboplatin + Paclitaxel | Pevonedistat 20 mg/m^2 in combination with carboplatin area under the plasma concentration (AUC) at the dose of 5 mg/min/mL, infusion, IV and paclitaxel 175 mg/m^2, infusion, IV, once on Day 1 in each 21-day treatment cycle followed by pevonedistat 20 mg/m^2 IV, once on Days 3 and 5 in each 21-day treatment cycle for up to 20 cycles or symptomatic deterioration or PD, or until treatment is discontinued for another reason. Pevonedistat was administered after the paclitaxel and carboplatin chemotherapy. Participants who completed Part A and provided consent for Part B continued treatment in Part B. |
|
|