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| ID | Type | Description | Link |
|---|---|---|---|
| GO01305 | Other Identifier | Hoffmann-La Roche |
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This Phase Ib, multicenter, single-arm, open-label study is designed to evaluate the effect of trastuzumab on QTcF interval and to characterize the effects of trastuzumab on carboplatin pharmacokinetics in patients with HER2-positive metastatic or locally advanced inoperable cancer.
The QT interval is a measure of time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. The QTcF interval is the QT interval as calculated using Fridericia's correction; the QTcB interval is the QT interval as calculated using Bazett's correction.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| carboplatin | Drug | Intravenous repeating dose |
| |
| docetaxel |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Corrected QT Interval Using Fridericia's Correction (QTcF) at Trastuzumab Steady State | Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Trastuzumab steady state was defined as the average of the 2 ECG measurements collected on Cycle 1 Day 8 (C1D8) and Cycle 2 Day 1 (C2D1) after the trastuzumab infusion. | Baseline, Cycle 1 Day 8 and Cycle 2 Day 1 |
| Maximum Observed Plasma Concentration (Cmax) of Carboplatin | 0 to 5 minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab) | |
| Area Under the Curve From Time Zero to 6 Hours Post Infusion (AUC0-6hr) of Carboplatin | AUC0-6hr = Area under the plasma concentration versus time curve from 0 to 6 hours post-infusion. | 0 to 5, 60 (±5), 120 (±10), 240 (±10), and 360 (±15) minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab) |
| Dose-Normalized Cmax (Cmax/D) of Carboplatin | Dose normalized Cmax is the maximum observed concentration of carboplatin in plasma normalized for different dose levels. | 0 to 5 minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab) |
| Geometric Mean Ratio of Cmax/D of Carboplatin | The geometric mean ratio of Cmax of carboplatin was defined as the Cmax/D of carboplatin on Cycle 1 Day 1 (in the absence of trastuzumab) divided by Cmax/D of carboplatin on Cycle 2 Day 1 (in the presence of trastuzumab). |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Corrected QT Interval Using Bazett's Correction (QTcB) at Trastuzumab Steady State | Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Bazette's formula (QTcB = QT divided by square root of RR). Trastuzumab steady state was defined as the average of the 2 ECG measurements collected on Cycle 1 Day 8 and Cycle 2 Day 1 after the trastuzumab infusion. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Harald Weber, M.D. | Genentech, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Scottsdale | Arizona | 85258 | United States | |||
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| ID | Title | Description |
|---|---|---|
| FG000 | Trastuzumab + Docetaxel + Carboplatin | Trastuzumab was administered at an initial dose of 6 milligrams per kilogram (mg/kg) of body weight given by intravenous (IV) infusion over 90 (±10) minutes on Cycle 1 Day 2 and Cycle 1 Day 8, followed by a maintenance dose of 6 mg/kg given by IV infusion on Day 1 of each subsequent treatment cycle (every 21 [±3] days). Docetaxel was administered as an IV dose of 75 milligrams per square meter (mg/m^2) of body surface area (BSA) on Day 1 of each study treatment cycle. Carboplatin was administered as an IV dose at a target area under the concentration-versus-time curve (AUC) of 6 milligrams per milliliter per minute (mg/mL/min) on Day 1 of each study treatment cycle. Study treatment continued until the Investigator decided to discontinue study therapy or for up to 12 months after the last participant was enrolled in the study, whichever came first. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Drug |
Intravenous repeating dose |
|
| trastuzumab | Drug | Intravenous repeating dose |
|
| 0 to 5 minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab) |
| Dose-Normalized AUC0-6hr (AUC0-6hr/D) of Carboplatin | AUC0-6hr/D = Area under the plasma concentration versus time curve from 0 to 6 hours post-infusion, normalized by carboplatin dose level. | 0 to 5, 60 (±5), 120 (±10), 240 (±10), and 360 (±15) minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab) |
| Geometric Mean Ratio of AUC0-6hr/D of Carboplatin | The geometric mean ratio of AUC0-6hr/D of carboplatin was defined as the AUC0-6hr/D of carboplatin on Cycle 1 Day 1 (in the absence of trastuzumab) divided by AUC0-6hr/D of carboplatin on Cycle 2 Day 1 (in the presence of trastuzumab). | 0 to 5, 60 (±5), 120 (±10), 240 (±10), and 360 (±15) minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab) |
| Plasma Decay Half-Life (t1/2) of Carboplatin | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 0 to 5, 60 (±5), 120 (±10), 240 (±10), and 360 (±15) minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab) |
| Maximum Observed Serum Concentration (Cmax) of Trastuzumab | 30 (±15) minutes after the end of the infusion on Cycle 1 Day 2, Cycle 1 Day 8, Cycle 2 Day 1, and Cycle 3 Day 1 |
| Minimum Observed Serum Trough Concentration (Cmin) of Trastuzumab | 15 (±15) minutes prior to the start of the trastuzumab infusion on Cycle 1 Day 2, Cycle 1 Day 8, Cycle 2 Day 1, and Cycle 3 Day 1 |
| Baseline, Cycle 1 Day 8 and Cycle 2 Day 1 |
| Baseline-adjusted QTcF, QTcB, PR Interval, and QRS Duration | For each postbaseline timepoint, a participant's corresponding baseline measure was subtracted from his or her average of the triplicate ECG measure to create a "baseline-adjusted" corresponding ECG measure for each participant at each postbaseline timepoint. | Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose) |
| Baseline-adjusted Heart Rate | For each postbaseline timepoint, a participant's corresponding baseline heart rate was subtracted from his or her average of the triplicate heart rate to create a "baseline-adjusted" corresponding heart rate for each participant at each postbaseline timepoint. | Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose) |
| Number of Participants Within Each Absolute QTc Interval Category | Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Participants with maximum QTc less than or equal to (<=) 450 msec, greater than (>) 450 to <=470 msec, >470 to <= 500 msec, or >500 msec were reported. | Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose) |
| Number of Participants With Increase From Baseline in QTc Interval | Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Participants with maximum increase from baseline of =>30msec, 30 to <60 msec (borderline) and >=60 msec (prolonged) were summarized. | Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose) |
| Number of Participants With New Abnormal U Waves on ECG | The incidence of abnormal U-wave changes from baseline was determined based on centrally read ECG tracings comparing each of the three triplicate readings from the post baseline ECG time points to the baseline ECG reading. At each time point, if at least one of the three triplicate readings was abnormal, the participant was counted as abnormal for that ECG timepoint as follows: a large U wave, inverted U wave, or T-U fusion compared with baseline was considered an abnormal significant change from baseline. | Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose) |
| Number of Participants With New Abnormal T Waves on ECG | The incidence of abnormal T-wave changes from baseline was determined based on centrally read ECG tracings comparing each of the three triplicate readings from the post baseline ECG time points to the baseline ECG reading. At each time point, if at least one of the three triplicate readings was abnormal, the participant was counted as abnormal for that ECG timepoint as follows: an inverted T, flat T, or biphasic T compared with baseline was considered an abnormal significant change from baseline. Additionally, nonspecific T-wave changes from baseline were considered as abnormal nonsignificant changes from baseline. T-wave changes from baseline due to ventricular conduction or left ventricular hypertrophy strain were considered not evaluable. | Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose) |
| Number of Participants With Abnormal Changes in PR Interval | Criteria for abnormal changes in PR interval were defined as: =>25 percentage (%) change from baseline, an absolute value >200 msec, or >=25% change from baseline and an absolute value >200 msec. | Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose) |
| Number of Participants With Abnormal Changes in QRS Interval | Criteria for abnormal changes in QRS interval were defined as: >=25% change from baseline, an absolute value >110 msec, or >=25% change from baseline and an absolute value >110 msec. | Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose) |
| Population Pharmacokinetics of Trastuzumab | As per planned analysis, separate population pharmacokinetic analysis results are not available for the current study as this analysis is based on pooled data from multiple studies. | 15 (±15) minutes prior to the start of the trastuzumab infusion, and 30 (±15) minutes after the end of the infusion on Cycle 1 Day 2, Cycle 1 Day 8, Cycle 2 Day 1, and Cycle 3 Day 1 |
| Beverly Hills |
| California |
| 90211 |
| United States |
| La Jolla | California | 92093 | United States |
| San Diego | California | 92123 | United States |
| Santa Rosa | California | 95403 | United States |
| Whittier | California | 90603 | United States |
| Miami | Florida | 33136 | United States |
| Wichita | Kansas | 67214-3728 | United States |
| Billings | Montana | 59101 | United States |
| Farmington | New Mexico | 87401 | United States |
| The Bronx | New York | 10461 | United States |
| Memphis | Tennessee | 38120 | United States |
| Nashville | Tennessee | 37232 | United States |
| Dallas | Texas | 75230 | United States |
| Galveston | Texas | 77555 | United States |
| Houston | Texas | 77024 | United States |
| Houston | Texas | 77030 | United States |
| San Antonio | Texas | 78229 | United States |
| Temple | Texas | 76508 | United States |
| Seattle | Washington | 98101 | United States |
| COMPLETED |
|
| NOT COMPLETED |
|
|
All enrolled participants
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Trastuzumab + Docetaxel + Carboplatin | Trastuzumab was administered at an initial dose of 6 mg/kg of body weight given by IV infusion over 90 (±10) minutes on Cycle 1 Day 2 and Cycle 1 Day 8, followed by a maintenance dose of 6 mg/kg given by IV infusion on Day 1 of each subsequent treatment cycle (every 21 [±3] days). Docetaxel was administered as an IV dose of 75 mg/m^2 of BSA on Day 1 of each study treatment cycle. Carboplatin was administered as an IV dose at a target AUC of 6 mg/mL/min on Day 1 of each study treatment cycle. Study treatment continued until the Investigator decided to discontinue study therapy or for up to 12 months after the last participant was enrolled in the study, whichever came first. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| 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 From Baseline in Corrected QT Interval Using Fridericia's Correction (QTcF) at Trastuzumab Steady State | Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Trastuzumab steady state was defined as the average of the 2 ECG measurements collected on Cycle 1 Day 8 (C1D8) and Cycle 2 Day 1 (C2D1) after the trastuzumab infusion. | ECG-evaluable participant population: received any trastuzumab, had at least 1 interpretable baseline ECG measurement recorded on C1D2 prior trastuzumab exposure, had at least 1 interpretable ECG measurement recorded on C1D8 or C2D1 corresponding to time of steady-state trastuzumab concentration, and no infusion reaction requiring drug treatments. | Posted | Mean | 90% Confidence Interval | milliseconds (msec) | Baseline, Cycle 1 Day 8 and Cycle 2 Day 1 |
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| Primary | Maximum Observed Plasma Concentration (Cmax) of Carboplatin | The pharmacokinetic (PK) analysis population for carboplatin included all participants who had a measurable ultrafiltrate or plasma carboplatin concentration at all nominal sampling time points. Participants for whom a full set of carboplatin PK samples in both Cycle 1 and Cycle 2 was not reported were excluded. | Posted | Mean | Standard Deviation | Microgram per milliliter (mcg/mL) | 0 to 5 minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab) |
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| Primary | Area Under the Curve From Time Zero to 6 Hours Post Infusion (AUC0-6hr) of Carboplatin | AUC0-6hr = Area under the plasma concentration versus time curve from 0 to 6 hours post-infusion. | The PK analysis population for carboplatin | Posted | Mean | Standard Deviation | Hour*microgram/milliliter (hr*mcg/mL) | 0 to 5, 60 (±5), 120 (±10), 240 (±10), and 360 (±15) minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab) |
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| Primary | Dose-Normalized Cmax (Cmax/D) of Carboplatin | Dose normalized Cmax is the maximum observed concentration of carboplatin in plasma normalized for different dose levels. | The PK analysis population for carboplatin | Posted | Mean | Standard Deviation | (mcg/mL)/(min*mg/mL) | 0 to 5 minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab) |
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| Secondary | Change From Baseline in Corrected QT Interval Using Bazett's Correction (QTcB) at Trastuzumab Steady State | Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Bazette's formula (QTcB = QT divided by square root of RR). Trastuzumab steady state was defined as the average of the 2 ECG measurements collected on Cycle 1 Day 8 and Cycle 2 Day 1 after the trastuzumab infusion. | ECG-evaluable participant population | Posted | Mean | 90% Confidence Interval | msec | Baseline, Cycle 1 Day 8 and Cycle 2 Day 1 |
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| Secondary | Baseline-adjusted QTcF, QTcB, PR Interval, and QRS Duration | For each postbaseline timepoint, a participant's corresponding baseline measure was subtracted from his or her average of the triplicate ECG measure to create a "baseline-adjusted" corresponding ECG measure for each participant at each postbaseline timepoint. | ECG-evaluable participant population. n=participants with available data at each timepoint. | Posted | Mean | Standard Deviation | msec | Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose) |
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| Secondary | Baseline-adjusted Heart Rate | For each postbaseline timepoint, a participant's corresponding baseline heart rate was subtracted from his or her average of the triplicate heart rate to create a "baseline-adjusted" corresponding heart rate for each participant at each postbaseline timepoint. | ECG-evaluable participant population. n=participants with available data at each timepoint. | Posted | Mean | Standard Deviation | beats per minute (bpm) | Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose) |
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| Secondary | Number of Participants Within Each Absolute QTc Interval Category | Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Participants with maximum QTc less than or equal to (<=) 450 msec, greater than (>) 450 to <=470 msec, >470 to <= 500 msec, or >500 msec were reported. | ECG-evaluable participant population. n=participants with available data at each timepoint. | Posted | Number | participants | Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose) |
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| Secondary | Number of Participants With Increase From Baseline in QTc Interval | Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Participants with maximum increase from baseline of =>30msec, 30 to <60 msec (borderline) and >=60 msec (prolonged) were summarized. | ECG-evaluable participant population. n=participants with available data at each timepoint. | Posted | Number | participants | Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose) |
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| Secondary | Number of Participants With New Abnormal U Waves on ECG | The incidence of abnormal U-wave changes from baseline was determined based on centrally read ECG tracings comparing each of the three triplicate readings from the post baseline ECG time points to the baseline ECG reading. At each time point, if at least one of the three triplicate readings was abnormal, the participant was counted as abnormal for that ECG timepoint as follows: a large U wave, inverted U wave, or T-U fusion compared with baseline was considered an abnormal significant change from baseline. | ECG-evaluable participant population. n=participants with available data at each timepoint. | Posted | Number | participants | Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose) |
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| Secondary | Number of Participants With New Abnormal T Waves on ECG | The incidence of abnormal T-wave changes from baseline was determined based on centrally read ECG tracings comparing each of the three triplicate readings from the post baseline ECG time points to the baseline ECG reading. At each time point, if at least one of the three triplicate readings was abnormal, the participant was counted as abnormal for that ECG timepoint as follows: an inverted T, flat T, or biphasic T compared with baseline was considered an abnormal significant change from baseline. Additionally, nonspecific T-wave changes from baseline were considered as abnormal nonsignificant changes from baseline. T-wave changes from baseline due to ventricular conduction or left ventricular hypertrophy strain were considered not evaluable. | ECG-evaluable participant population. n=participants with available data at each timepoint. | Posted | Number | participants | Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose) |
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| Secondary | Number of Participants With Abnormal Changes in PR Interval | Criteria for abnormal changes in PR interval were defined as: =>25 percentage (%) change from baseline, an absolute value >200 msec, or >=25% change from baseline and an absolute value >200 msec. | ECG-evaluable participant population. n=participants with available data at each timepoint. | Posted | Number | participants | Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose) |
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| Secondary | Number of Participants With Abnormal Changes in QRS Interval | Criteria for abnormal changes in QRS interval were defined as: >=25% change from baseline, an absolute value >110 msec, or >=25% change from baseline and an absolute value >110 msec. | ECG-evaluable participant population. n=participants with available data at each timepoint. | Posted | Number | participants | Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose) |
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| Secondary | Population Pharmacokinetics of Trastuzumab | As per planned analysis, separate population pharmacokinetic analysis results are not available for the current study as this analysis is based on pooled data from multiple studies. | Not Posted | 15 (±15) minutes prior to the start of the trastuzumab infusion, and 30 (±15) minutes after the end of the infusion on Cycle 1 Day 2, Cycle 1 Day 8, Cycle 2 Day 1, and Cycle 3 Day 1 | ||||||||||||||||||||||||||||||||
| Primary | Geometric Mean Ratio of Cmax/D of Carboplatin | The geometric mean ratio of Cmax of carboplatin was defined as the Cmax/D of carboplatin on Cycle 1 Day 1 (in the absence of trastuzumab) divided by Cmax/D of carboplatin on Cycle 2 Day 1 (in the presence of trastuzumab). | The PK analysis population for carboplatin | Posted | Geometric Mean | 90% Confidence Interval | ratio | 0 to 5 minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab) |
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| Primary | Dose-Normalized AUC0-6hr (AUC0-6hr/D) of Carboplatin | AUC0-6hr/D = Area under the plasma concentration versus time curve from 0 to 6 hours post-infusion, normalized by carboplatin dose level. | The PK analysis population for carboplatin | Posted | Mean | Standard Deviation | (hr*mcg/mL)/(min*mg/mL) | 0 to 5, 60 (±5), 120 (±10), 240 (±10), and 360 (±15) minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab) |
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| Primary | Geometric Mean Ratio of AUC0-6hr/D of Carboplatin | The geometric mean ratio of AUC0-6hr/D of carboplatin was defined as the AUC0-6hr/D of carboplatin on Cycle 1 Day 1 (in the absence of trastuzumab) divided by AUC0-6hr/D of carboplatin on Cycle 2 Day 1 (in the presence of trastuzumab). | The PK analysis population for carboplatin | Posted | Geometric Mean | 90% Confidence Interval | ratio | 0 to 5, 60 (±5), 120 (±10), 240 (±10), and 360 (±15) minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab) |
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| Primary | Plasma Decay Half-Life (t1/2) of Carboplatin | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | The PK analysis population for carboplatin. n=participants with available data at each timepoint. | Posted | Mean | Standard Deviation | hr | 0 to 5, 60 (±5), 120 (±10), 240 (±10), and 360 (±15) minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab) |
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| Primary | Maximum Observed Serum Concentration (Cmax) of Trastuzumab | The PK analysis population for trastuzumab included all participants who had at least 1 measurable serum trastuzumab concentration collected at a nominal sampling timepoint. Participants who did not receive a trastuzumab dose or for whom no trastuzumab PK samples were reported were excluded. n=participants with available data at each timepoint. | Posted | Geometric Mean | 95% Confidence Interval | mcg/mL | 30 (±15) minutes after the end of the infusion on Cycle 1 Day 2, Cycle 1 Day 8, Cycle 2 Day 1, and Cycle 3 Day 1 |
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| Primary | Minimum Observed Serum Trough Concentration (Cmin) of Trastuzumab | PK analysis population for trastuzumab. n=participants with available data at each timepoint. | Posted | Geometric Mean | 95% Confidence Interval | mcg/mL | 15 (±15) minutes prior to the start of the trastuzumab infusion on Cycle 1 Day 2, Cycle 1 Day 8, Cycle 2 Day 1, and Cycle 3 Day 1 |
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Baseline up to study completion/early termination (28 to 42 days after the last administration of study treatment) (maximum treatment duration = 163 weeks)
The safety-evaluable participant analysis population included all participants who were treated with at least one dose of any treatment of the study regimen.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Trastuzumab + Docetaxel + Carboplatin | Trastuzumab was administered at an initial dose of 6 mg/kg of body weight given by IV infusion over 90 (±10) minutes on Cycle 1 Day 2 and Cycle 1 Day 8, followed by a maintenance dose of 6 mg/kg given by IV infusion on Day 1 of each subsequent treatment cycle (every 21 [±3] days). Docetaxel was administered as an IV dose of 75 mg/m^2 of BSA on Day 1 of each study treatment cycle. Carboplatin was administered as an IV dose at a target AUC of 6 mg/mL/min on Day 1 of each study treatment cycle. Study treatment continued until the Investigator decided to discontinue study therapy or for up to 12 months after the last participant was enrolled in the study, whichever came first. | 26 | 58 | 56 | 58 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Diverticular perforation | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Haematemesis | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Oesophageal spasm | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Clostridium difficile colitis | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Peritonitis | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Diabetic ketoacidosis | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Female genital tract fistula | Reproductive system and breast disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Electrical burn | Injury, poisoning and procedural complications | MedDRA 15.0 | Non-systematic Assessment |
| |
| Haemorrhagic stroke | Nervous system disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutrophil count decreased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Gamma- glutamyltransferase increased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Abdominal pain lower | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Iron deficiency | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Candidiasis | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 15.0 | Non-systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 15.0 | Non-systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA 15.0 | Non-systematic Assessment |
|
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-LaRoche | 800-821-8590 | genentech@druginfo.com |
| ID | Term |
|---|---|
| D016190 | Carboplatin |
| D000077143 | Docetaxel |
| D000068878 | Trastuzumab |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
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