Solid Tumor
Conditions
Brief summary
This study will evaluate the safety, tolerability, and pharmacokinetics of the combination of rhuMab 2C4 (Perjeta) and docetaxel (Taxotere) in participants with advanced solid tumors that have progressed during or after standard therapy, or for which no standard therapy is available. Participants will be enrolled and evaluated for dose-limiting toxicities (DLTs) in escalating-dose cohorts in order to determine the maximum tolerated dose (MTD).
Interventions
DRUGDocetaxel
Participants will receive docetaxel on Day 1 of each 3-week cycle as 60, 75, or 100 mg/m\^2 via IV infusion. Treatment may continue until disease progression, unacceptable toxicity, or consent withdrawal.
DRUGRhuMab 2C4
Participants will receive rhuMab 2C4 on Day 1 of each 3-week cycle as 420 mg via IV infusion. For Cycle 1 ony, rhuMab will be administered on Day 2, at least 24 hours after docetaxel and following an initial 840-mg loading dose. Treatment may continue until disease progression, unacceptable toxicity, or consent withdrawal.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults at least 18 years of age * Easter Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Life expectancy at least 12 weeks * Locally advanced or metastatic solid tumor with at least 1 measurable lesion, which has progressed during/after standard therapy * Human epidermal growth factor receptor 2 (HER2)-negative among participants with breast cancer * Negative pregnancy test or use of an adequate contraceptive method among women of childbearing potential * Adequate hematologic, hepatic, and renal function * Signed informed consent, histologically or cytologicall confirmed advanced solid tumor, adequate cardiac function as documented by LVEF \>50% by ECHO or MUGA
Exclusion criteria
* Clinical evidence of central nervous system (CNS) metastases * Prior chemotherapy, radiotherapy, or immunotherapy within 4 weeks, or hormone therapy within 2 weeks of study Day 1 * History of neuropathy Grade 2 or worse, or any unresolved residual chemotherapy effects * Prior HER2-active agents or docetaxel * Any investigational agent within 28 days of study drug * Prior cumulative doxorubicin dose greater than (\>) 360 mg/m\^2 or equivalent * Significant cardiovascular disease * Active/uncontrolled concurrent illness or infection- * Major surgery or trauma within 4 weeks of study Day 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of Docetaxel in Combination of Pertuzumab | Cycle 1 Up to Day 15 | A prior dose level was defined as an MTD if at a certain dose level, there were greater than or equal to (≥) 2 out of 6 participants who had Dose Limiting Toxicities (DLTs). If there were no DLTs or DLTs were seen in less than (\<) 2 participants in the highest dose level, that was considered as MTD. Participants received escalating doses of docetaxel and pertuzumab until DLTs were observed. DLTs were defined as any of the following: 1) Any non-hematological toxicity ≥ Grade 3 according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management, 2) Grade 4 neutropenia lasting greater than (\>) 7 days, 3) Febrile neutropenia, 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion or 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) for Pertuzumab in Combination With Docetaxel | Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22 | Cmax refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and prior to the administration of a second dose and is measures as micrograms per milliliter (μg/mL). |
| Area Under the Concentration Curve From Time Zero to the Last Visit (AUC [0-last]) for Pertuzumab in Combination With Docetaxel | Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22 | The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC0-last is calculated from time 0 (prior to administration of medication) to last measured data point. The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as micrograms times days per milliliter (μg\*day/mL). |
| AUC From Time Zero to Infinity (AUC [0-infinity]) for Pertuzumab in Combination With Docetaxel | Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22 | The AUC0-infinity is calculated from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as μg\*day/mL. |
| Clearance (Cl) of Pertuzimab in Combination With Docetaxel | Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22 | Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It is measured as milliliters per day (mL/day). |
| Volume of Distribution (Vz) at Steady State of Pertuzumab in Combination With Docetaxel | Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22 | The volume of distribution at steady state (Vz), also known as apparent volume of distribution, is a pharmacological, theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma. |
| Mean Residence Time (MRT) of Pertuzumab | Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22 | MRT is the average time that pertuzumab is present in the systemic circulation and is measured in days. |
| Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Weeks 7 (Cycle 2),13 (Cycle 4) and Final Visit Up to 22 weeks | Best Overall response was evaluated as Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD). CR: complete disappearance of all target lesions. PR: at least a 30 percent (%) decrease in the sum of the longest diameters. SD: neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of the longest diameters since the treatment started. PD: at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters of the target lesions recorded since the treatment started, including screening, or the appearance of one or more new lesions. If participants withdrew due to insufficient therapeutic response or death and had no tumor measurements at the final visit, they were counted under progressive disease for final visit. |
| Plasma Decay Half Life (t1/2) for Pertuzumab in Combination With Docetaxel | Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22 | The biological half-life or terminal half-life of pertuzumab is the time in days it takes for it to lose half of its pharmacologic activity. |
| t1/2 for Docetaxel Alone and in Combination With Pertuzumab | Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose | The biological half-life or terminal half-life of docetaxel is the time in hours it takes for it to lose half of its pharmacologic activity. Data for docetaxel alone arms were analyzed for the timepoints on Day 1 prior to the administration of pertuzumab. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. |
| Tmax for Docetaxel Alone and in Combination With Pertuzumab | Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose | Tmax is defined as the time after administration of a drug when the maximum plasma concentration is reached; Data for docetaxel alone arms were analyzed for the timepoints on Day 1 prior to the administration of pertuzumab. When the rate of absorption equals the rate of elimination. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. |
| Cmax for Docetaxel Alone and in Combination With Pertuzumab | Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose | Cmax refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and prior to the administration of a second dose and is measures as nanograms per milliliter (ng/mL). The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. |
| AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab | Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose | The AUC0-infinity is calculated from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as ng\*h/mL. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. |
| Vss for Docetaxel Alone and in Combination With Pertuzumab | Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose | The volume of distribution at steady state (Vss), also known as apparent volume of distribution, is a pharmacological, theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. |
| CL for Docetaxel Alone and in Combination With Pertuzumab | Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose | Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It is measured as milliliters per hour per meter squared (mL/h/m\^2). The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. |
| Number of Participants With DLTs | From Baseline until 4 weeks after the end of treatment | DLTs were defined as any of the following: 1) Any non-hematological toxicity greter than or equal to (≥) Grade 3 according t0 CTCAE version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management, 2) Grade 4 neutropenia lasting greater than (\>) 7 days, 3) Febrile neutropenia, 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion or 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds. |
| Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Baseline, Weeks 7(Cycle 2), 13 (Cycle 4) and Final Visit Up to Week 22 | Ejection fraction (EF) is the fraction of outbound blood pumped from the heart with each heartbeat. It is commonly measured by echocardiogram and serves as a general measure of a person's cardiac function. Changes in LVEF were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria. The decrease in LVEF has been categorized as follows: A) Increase, no change, decrease from baseline less than (\<) 10%; B) Absolute value \<50% and decrease from baseline greater than or equal to (≥) 10%; C) Absolute value \<50% and decrease from baseline≥15% ; D) Other. If participants withdrew due to insufficient therapeutic response or death and had no tumor measurements at the final visit, they were counted under progressive disease for final visit. |
Countries
Netherlands, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel 60 Plus (+) Pertuzumab 1050 Participants received 60 mg/m\^2 docetaxel and 1050 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication. | 6 |
| Docetaxel 75 + Pertuzumab 1050 Participants received 75 mg/m\^2 docetaxel and 1050 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication. | 2 |
| Docetaxel 75 + Pertuzumab 420 Participants received 75 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication. | 6 |
| Docetaxel 100 + Pertuzumab 420 Participants received 100 mg/m\^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication. | 5 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1: First 6 Cycles | Adverse Event | 2 | 1 | 0 | 1 |
| Period 1: First 6 Cycles | Completed 6 Cycles of Therapy | 1 | 1 | 4 | 2 |
| Period 1: First 6 Cycles | Insufficient Therapeutic Response | 2 | 0 | 2 | 2 |
| Period 1: First 6 Cycles | Refused Treatment | 1 | 0 | 0 | 0 |
| Period 2: Extension Phase | Adverse Event | 0 | 0 | 1 | 0 |
| Period 2: Extension Phase | Insufficient Therapeutic Response | 1 | 0 | 2 | 0 |
| Period 2: Extension Phase | Refused Treatment | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Docetaxel 60 Plus (+) Pertuzumab 1050 | Docetaxel 75 + Pertuzumab 1050 | Docetaxel 75 + Pertuzumab 420 | Docetaxel 100 + Pertuzumab 420 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 58.2 years STANDARD_DEVIATION 5.38 | 62.5 years STANDARD_DEVIATION 9.19 | 59.5 years STANDARD_DEVIATION 6.06 | 45.0 years STANDARD_DEVIATION 20.21 | 55.6 years STANDARD_DEVIATION 12.55 |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 1 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 5 Participants | 2 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 2 / 2 | 6 / 6 | 5 / 5 |
| serious Total, serious adverse events | 3 / 6 | 2 / 2 | 0 / 6 | 3 / 5 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of Docetaxel in Combination of Pertuzumab
A prior dose level was defined as an MTD if at a certain dose level, there were greater than or equal to (≥) 2 out of 6 participants who had Dose Limiting Toxicities (DLTs). If there were no DLTs or DLTs were seen in less than (\<) 2 participants in the highest dose level, that was considered as MTD. Participants received escalating doses of docetaxel and pertuzumab until DLTs were observed. DLTs were defined as any of the following: 1) Any non-hematological toxicity ≥ Grade 3 according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management, 2) Grade 4 neutropenia lasting greater than (\>) 7 days, 3) Febrile neutropenia, 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion or 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds.
Time frame: Cycle 1 Up to Day 15
Population: Safety Population: included all participants who received any amount of study medication and who had at least one post-baseline safety follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entire Study Population | Maximum Tolerated Dose (MTD) of Docetaxel in Combination of Pertuzumab | 75.0 mg/m^2 |
Secondary
Area Under the Concentration Curve From Time Zero to the Last Visit (AUC [0-last]) for Pertuzumab in Combination With Docetaxel
The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC0-last is calculated from time 0 (prior to administration of medication) to last measured data point. The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as micrograms times days per milliliter (μg\*day/mL).
Time frame: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22
Population: ITT population; Participants in any cohort infused with the specified dose of pertuzumab were included in analysis.~n = number of participants analyzed at the specified timepoint for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Entire Study Population | Area Under the Concentration Curve From Time Zero to the Last Visit (AUC [0-last]) for Pertuzumab in Combination With Docetaxel | Cycle 1 (n=8,11,0) | 2390 μg*day/mL | Standard Deviation 584 |
| Entire Study Population | Area Under the Concentration Curve From Time Zero to the Last Visit (AUC [0-last]) for Pertuzumab in Combination With Docetaxel | Cycle 2 (n=7,0,10) | 3500 μg*day/mL | Standard Deviation 551 |
| Pertuzumab 840 | Area Under the Concentration Curve From Time Zero to the Last Visit (AUC [0-last]) for Pertuzumab in Combination With Docetaxel | Cycle 1 (n=8,11,0) | 1749 μg*day/mL | Standard Deviation 543 |
| Pertuzumab 840 | Area Under the Concentration Curve From Time Zero to the Last Visit (AUC [0-last]) for Pertuzumab in Combination With Docetaxel | Cycle 2 (n=7,0,10) | NA μg*day/mL | — |
| Pertuzumab 420 | Area Under the Concentration Curve From Time Zero to the Last Visit (AUC [0-last]) for Pertuzumab in Combination With Docetaxel | Cycle 1 (n=8,11,0) | NA μg*day/mL | — |
| Pertuzumab 420 | Area Under the Concentration Curve From Time Zero to the Last Visit (AUC [0-last]) for Pertuzumab in Combination With Docetaxel | Cycle 2 (n=7,0,10) | 1491 μg*day/mL | Standard Deviation 472 |
Secondary
AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab
The AUC0-infinity is calculated from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as ng\*h/mL. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1.
Time frame: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose
Population: ITT population; Data from Cohort 2 (docetaxel 75 mg/m\^2 and pertuzumab 1050 mg) were excluded because there were only 2 participant data. It was planned not to report PK data, if less than or equal to 2 participants were analyzed. n= number of participants analyzed at the specified cycle.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Entire Study Population | AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | 1838 ng*h/mL | Standard Deviation 244 |
| Entire Study Population | AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | NA ng*h/mL | — |
| Pertuzumab 840 | AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | NA ng*h/mL | — |
| Pertuzumab 840 | AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | 1734 ng*h/mL | Standard Deviation 409 |
| Pertuzumab 420 | AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | 3744 ng*h/mL | Standard Deviation 1304 |
| Pertuzumab 420 | AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | NA ng*h/mL | — |
| Docetaxel 100 + Pertuzumab 420 | AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | NA ng*h/mL | — |
| Docetaxel 100 + Pertuzumab 420 | AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | 3496 ng*h/mL | Standard Deviation 1211 |
| Docetaxel 100 Alone | AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | 5930 ng*h/mL | Standard Deviation 2137 |
| Docetaxel 100 Alone | AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | NA ng*h/mL | — |
| Docetaxel 100 + Pertuzumab 420 | AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | NA ng*h/mL | — |
| Docetaxel 100 + Pertuzumab 420 | AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | 5218 ng*h/mL | Standard Deviation 2216 |
Secondary
AUC From Time Zero to Infinity (AUC [0-infinity]) for Pertuzumab in Combination With Docetaxel
The AUC0-infinity is calculated from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as μg\*day/mL.
Time frame: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22
Population: ITT population; Participants in any cohort infused with the specified dose of pertuzumab were included in analysis.~n = number of participants analyzed at the specified timepoint for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Entire Study Population | AUC From Time Zero to Infinity (AUC [0-infinity]) for Pertuzumab in Combination With Docetaxel | Cycle 1 (n=8,11,0) | 3951 μg*day/mL | Standard Deviation 919 |
| Entire Study Population | AUC From Time Zero to Infinity (AUC [0-infinity]) for Pertuzumab in Combination With Docetaxel | Cycle 2 (n=7,0,10) | 6856 μg*day/mL | Standard Deviation 2335 |
| Pertuzumab 840 | AUC From Time Zero to Infinity (AUC [0-infinity]) for Pertuzumab in Combination With Docetaxel | Cycle 1 (n=8,11,0) | 2796 μg*day/mL | Standard Deviation 967 |
| Pertuzumab 840 | AUC From Time Zero to Infinity (AUC [0-infinity]) for Pertuzumab in Combination With Docetaxel | Cycle 2 (n=7,0,10) | NA μg*day/mL | — |
| Pertuzumab 420 | AUC From Time Zero to Infinity (AUC [0-infinity]) for Pertuzumab in Combination With Docetaxel | Cycle 1 (n=8,11,0) | NA μg*day/mL | — |
| Pertuzumab 420 | AUC From Time Zero to Infinity (AUC [0-infinity]) for Pertuzumab in Combination With Docetaxel | Cycle 2 (n=7,0,10) | 2762 μg*day/mL | Standard Deviation 892 |
Secondary
Clearance (Cl) of Pertuzimab in Combination With Docetaxel
Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It is measured as milliliters per day (mL/day).
Time frame: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22
Population: ITT population; Participants in any cohort infused with the specified dose of pertuzumab were included in analysis.~n = number of participants analyzed at the specified timepoint for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Entire Study Population | Clearance (Cl) of Pertuzimab in Combination With Docetaxel | Cycle 1 (n=8,11,0) | 282 mL/day | Standard Deviation 83 |
| Entire Study Population | Clearance (Cl) of Pertuzimab in Combination With Docetaxel | Cycle 2 (n=7,0,10) | 167 mL/day | Standard Deviation 49 |
| Pertuzumab 840 | Clearance (Cl) of Pertuzimab in Combination With Docetaxel | Cycle 1 (n=8,11,0) | 329 mL/day | Standard Deviation 97 |
| Pertuzumab 840 | Clearance (Cl) of Pertuzimab in Combination With Docetaxel | Cycle 2 (n=7,0,10) | NA mL/day | — |
| Pertuzumab 420 | Clearance (Cl) of Pertuzimab in Combination With Docetaxel | Cycle 1 (n=8,11,0) | NA mL/day | — |
| Pertuzumab 420 | Clearance (Cl) of Pertuzimab in Combination With Docetaxel | Cycle 2 (n=7,0,10) | 169 mL/day | Standard Deviation 60 |
Secondary
CL for Docetaxel Alone and in Combination With Pertuzumab
Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It is measured as milliliters per hour per meter squared (mL/h/m\^2). The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1.
Time frame: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose
Population: ITT population; Data from Cohort 2 (docetaxel 75 mg/m\^2 and pertuzumab 1050 mg) were excluded because there were only 2 participant data. It was planned not to report PK data, if less than or equal to 2 participants were analyzed. n= number of participants analyzed at the specified cycle.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Entire Study Population | CL for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | 33128 mL/h/m^2 | Standard Deviation 4396 |
| Entire Study Population | CL for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | NA mL/h/m^2 | — |
| Pertuzumab 840 | CL for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | NA mL/h/m^2 | — |
| Pertuzumab 840 | CL for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | 35813 mL/h/m^2 | Standard Deviation 6216 |
| Pertuzumab 420 | CL for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | 22013 mL/h/m^2 | Standard Deviation 7031 |
| Pertuzumab 420 | CL for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | NA mL/h/m^2 | — |
| Docetaxel 100 + Pertuzumab 420 | CL for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | NA mL/h/m^2 | — |
| Docetaxel 100 + Pertuzumab 420 | CL for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | 23747 mL/h/m^2 | Standard Deviation 8175 |
| Docetaxel 100 Alone | CL for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | 18913 mL/h/m^2 | Standard Deviation 7245 |
| Docetaxel 100 Alone | CL for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | NA mL/h/m^2 | — |
| Docetaxel 100 + Pertuzumab 420 | CL for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | NA mL/h/m^2 | — |
| Docetaxel 100 + Pertuzumab 420 | CL for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | 22976 mL/h/m^2 | Standard Deviation 12679 |
Secondary
Cmax for Docetaxel Alone and in Combination With Pertuzumab
Cmax refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and prior to the administration of a second dose and is measures as nanograms per milliliter (ng/mL). The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1.
Time frame: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose
Population: ITT population; Data from Cohort 2 (docetaxel 75 mg/m\^2 and pertuzumab 1050 mg) were excluded because there were only 2 participant data. It was planned not to report PK data, if less than or equal to 2 participants were analyzed. n= number of participants analyzed at the specified cycle.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Entire Study Population | Cmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | 1642 ng/mL | Standard Deviation 274 |
| Entire Study Population | Cmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | NA ng/mL | — |
| Pertuzumab 840 | Cmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | NA ng/mL | — |
| Pertuzumab 840 | Cmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | 1695 ng/mL | Standard Deviation 331 |
| Pertuzumab 420 | Cmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | 3128 ng/mL | Standard Deviation 895 |
| Pertuzumab 420 | Cmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | NA ng/mL | — |
| Docetaxel 100 + Pertuzumab 420 | Cmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | NA ng/mL | — |
| Docetaxel 100 + Pertuzumab 420 | Cmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | 2722 ng/mL | Standard Deviation 912 |
| Docetaxel 100 Alone | Cmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | 5450 ng/mL | Standard Deviation 1867 |
| Docetaxel 100 Alone | Cmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | NA ng/mL | — |
| Docetaxel 100 + Pertuzumab 420 | Cmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | NA ng/mL | — |
| Docetaxel 100 + Pertuzumab 420 | Cmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | 4705 ng/mL | Standard Deviation 1871 |
Secondary
Maximum Observed Plasma Concentration (Cmax) for Pertuzumab in Combination With Docetaxel
Cmax refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and prior to the administration of a second dose and is measures as micrograms per milliliter (μg/mL).
Time frame: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22
Population: ITT population; Participants in any cohort infused with the specified dose of pertuzumab were included in analysis. n = number of participants analyzed at the specified timepoint for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Entire Study Population | Maximum Observed Plasma Concentration (Cmax) for Pertuzumab in Combination With Docetaxel | Cycle 1 (n=8,11,0) | 301.0 μg/mL | Standard Deviation 93 |
| Entire Study Population | Maximum Observed Plasma Concentration (Cmax) for Pertuzumab in Combination With Docetaxel | Cycle 2 (n=7,0,10) | 368.0 μg/mL | Standard Deviation 79 |
| Pertuzumab 840 | Maximum Observed Plasma Concentration (Cmax) for Pertuzumab in Combination With Docetaxel | Cycle 1 (n=8,11,0) | 255.0 μg/mL | Standard Deviation 84 |
| Pertuzumab 840 | Maximum Observed Plasma Concentration (Cmax) for Pertuzumab in Combination With Docetaxel | Cycle 2 (n=7,0,10) | NA μg/mL | — |
| Pertuzumab 420 | Maximum Observed Plasma Concentration (Cmax) for Pertuzumab in Combination With Docetaxel | Cycle 1 (n=8,11,0) | NA μg/mL | — |
| Pertuzumab 420 | Maximum Observed Plasma Concentration (Cmax) for Pertuzumab in Combination With Docetaxel | Cycle 2 (n=7,0,10) | 150.0 μg/mL | Standard Deviation 43 |
Secondary
Mean Residence Time (MRT) of Pertuzumab
MRT is the average time that pertuzumab is present in the systemic circulation and is measured in days.
Time frame: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22
Population: ITT population; Participants in any cohort infused with the specified dose of pertuzumab were included in analysis.~n = number of participants analyzed at the specified timepoint for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Entire Study Population | Mean Residence Time (MRT) of Pertuzumab | Cycle 1 (n=8,11,0) | 17.8 days | Standard Deviation 5.8 |
| Entire Study Population | Mean Residence Time (MRT) of Pertuzumab | Cycle 2 (n=7,0,10) | 29.5 days | Standard Deviation 18.5 |
| Pertuzumab 840 | Mean Residence Time (MRT) of Pertuzumab | Cycle 1 (n=8,11,0) | 15.8 days | Standard Deviation 6.7 |
| Pertuzumab 840 | Mean Residence Time (MRT) of Pertuzumab | Cycle 2 (n=7,0,10) | NA days | — |
| Pertuzumab 420 | Mean Residence Time (MRT) of Pertuzumab | Cycle 1 (n=8,11,0) | NA days | — |
| Pertuzumab 420 | Mean Residence Time (MRT) of Pertuzumab | Cycle 2 (n=7,0,10) | 25.8 days | Standard Deviation 13.2 |
Secondary
Number of Participants With DLTs
DLTs were defined as any of the following: 1) Any non-hematological toxicity greter than or equal to (≥) Grade 3 according t0 CTCAE version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management, 2) Grade 4 neutropenia lasting greater than (\>) 7 days, 3) Febrile neutropenia, 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion or 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds.
Time frame: From Baseline until 4 weeks after the end of treatment
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entire Study Population | Number of Participants With DLTs | 0 number of participants |
| Pertuzumab 840 | Number of Participants With DLTs | 2 number of participants |
| Pertuzumab 420 | Number of Participants With DLTs | 0 number of participants |
| Docetaxel 100 + Pertuzumab 420 | Number of Participants With DLTs | 2 number of participants |
Secondary
Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
Best Overall response was evaluated as Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD). CR: complete disappearance of all target lesions. PR: at least a 30 percent (%) decrease in the sum of the longest diameters. SD: neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of the longest diameters since the treatment started. PD: at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters of the target lesions recorded since the treatment started, including screening, or the appearance of one or more new lesions. If participants withdrew due to insufficient therapeutic response or death and had no tumor measurements at the final visit, they were counted under progressive disease for final visit.
Time frame: Weeks 7 (Cycle 2),13 (Cycle 4) and Final Visit Up to 22 weeks
Population: ITT population; n = number of participants still receiving treatment at the specified cycle for each arm respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entire Study Population | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 2: CR (n=6,1,6,4) | 0.0 percentage of participants |
| Entire Study Population | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Final visit:PR (n=6,2,6,5) | 0.0 percentage of participants |
| Entire Study Population | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 4:PD (n=5,1,5,3) | 20.0 percentage of participants |
| Entire Study Population | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 2:SD (n=6,1,6,4) | 83.3 percentage of participants |
| Entire Study Population | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 4:Missing (n=5,1,5,3) | 0.0 percentage of participants |
| Entire Study Population | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Final visit:CR (n=6,2,6,5) | 0.0 percentage of participants |
| Entire Study Population | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 2:PD (n=6,1,6,4) | 16.7 percentage of participants |
| Entire Study Population | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 2:PR (n=6,1,6,4) | 0.0 percentage of participants |
| Entire Study Population | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Final visit:PD (n=6,2,6,5) | 50.0 percentage of participants |
| Entire Study Population | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 2:Missing (n=6,1,6,4) | 0.0 percentage of participants |
| Entire Study Population | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 4:CR (n=5,1,5,3) | 0.0 percentage of participants |
| Entire Study Population | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Final visit:SD (n=6,2,6,5) | 33.3 percentage of participants |
| Entire Study Population | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 4:PR (n=5,1,5,3) | 0.0 percentage of participants |
| Entire Study Population | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Final visit:Missing (n=6,2,6,5) | 16.7 percentage of participants |
| Entire Study Population | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 4:SD (n=5,1,5,3) | 80.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 4:SD (n=5,1,5,3) | 100.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Final visit:PR (n=6,2,6,5) | 0.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 2:Missing (n=6,1,6,4) | 0.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 4:PD (n=5,1,5,3) | 0.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 2:PR (n=6,1,6,4) | 0.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Final visit:CR (n=6,2,6,5) | 0.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Final visit:SD (n=6,2,6,5) | 50.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 4:Missing (n=5,1,5,3) | 0.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 2:SD (n=6,1,6,4) | 100.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 4:PR (n=5,1,5,3) | 0.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Final visit:Missing (n=6,2,6,5) | 50.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Final visit:PD (n=6,2,6,5) | 0.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 4:CR (n=5,1,5,3) | 0.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 2:PD (n=6,1,6,4) | 0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 2: CR (n=6,1,6,4) | 0.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 4:SD (n=5,1,5,3) | 40.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 2: CR (n=6,1,6,4) | 0.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 2:PR (n=6,1,6,4) | 0.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 2:SD (n=6,1,6,4) | 83.3 percentage of participants |
| Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 2:PD (n=6,1,6,4) | 16.7 percentage of participants |
| Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 2:Missing (n=6,1,6,4) | 0.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 4:CR (n=5,1,5,3) | 0.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 4:PR (n=5,1,5,3) | 20.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 4:PD (n=5,1,5,3) | 40.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 4:Missing (n=5,1,5,3) | 0.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Final visit:CR (n=6,2,6,5) | 0.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Final visit:PR (n=6,2,6,5) | 16.7 percentage of participants |
| Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Final visit:SD (n=6,2,6,5) | 33.3 percentage of participants |
| Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Final visit:PD (n=6,2,6,5) | 50.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Final visit:Missing (n=6,2,6,5) | 0.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 4:PR (n=5,1,5,3) | 0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 2:PR (n=6,1,6,4) | 0.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Final visit:PR (n=6,2,6,5) | 0.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 4:CR (n=5,1,5,3) | 0.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 2:Missing (n=6,1,6,4) | 0.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 2: CR (n=6,1,6,4) | 0.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Final visit:SD (n=6,2,6,5) | 20.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 2:PD (n=6,1,6,4) | 25.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 2:SD (n=6,1,6,4) | 75.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Final visit:Missing (n=6,2,6,5) | 20.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 4:Missing (n=5,1,5,3) | 0.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 4:PD (n=5,1,5,3) | 33.3 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Final visit:PD (n=6,2,6,5) | 60.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Final visit:CR (n=6,2,6,5) | 0.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Cycle 4:SD (n=5,1,5,3) | 66.7 percentage of participants |
Secondary
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint
Ejection fraction (EF) is the fraction of outbound blood pumped from the heart with each heartbeat. It is commonly measured by echocardiogram and serves as a general measure of a person's cardiac function. Changes in LVEF were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria. The decrease in LVEF has been categorized as follows: A) Increase, no change, decrease from baseline less than (\<) 10%; B) Absolute value \<50% and decrease from baseline greater than or equal to (≥) 10%; C) Absolute value \<50% and decrease from baseline≥15% ; D) Other. If participants withdrew due to insufficient therapeutic response or death and had no tumor measurements at the final visit, they were counted under progressive disease for final visit.
Time frame: Baseline, Weeks 7(Cycle 2), 13 (Cycle 4) and Final Visit Up to Week 22
Population: ITT population; n = number of participants still receiving treatment at the specified cycle for each arm, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entire Study Population | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Final Visit: B (n=3,1,5,2) | 0.0 percentage of participants |
| Entire Study Population | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Final Visit: D (n=3,1,5,2) | 33.3 percentage of participants |
| Entire Study Population | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 4: D (n=5,1,4,3) | 0.0 percentage of participants |
| Entire Study Population | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 2: A (n=6,1,6,4) | 83.3 percentage of participants |
| Entire Study Population | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Final Visit: A (n=3,1,5,2) | 66.7 percentage of participants |
| Entire Study Population | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 2: C (n=6,1,6,4) | 0.0 percentage of participants |
| Entire Study Population | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 2: D (n=6,1,6,4) | 16.7 percentage of participants |
| Entire Study Population | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 2: B (n=6,1,6,4) | 0.0 percentage of participants |
| Entire Study Population | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Final Visit: C (n=3,1,5,2) | 0.0 percentage of participants |
| Entire Study Population | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 4: A (n=5,1,4,3) | 100.0 percentage of participants |
| Entire Study Population | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 4: B (n=5,1,4,3) | 0.0 percentage of participants |
| Entire Study Population | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 4: C (n=5,1,4,3) | 0.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 2: B (n=6,1,6,4) | 0.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 4: C (n=5,1,4,3) | 0.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 2: D (n=6,1,6,4) | 0.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Final Visit: A (n=3,1,5,2) | 100.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Final Visit: B (n=3,1,5,2) | 0.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 4: D (n=5,1,4,3) | 0.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 2: A (n=6,1,6,4) | 100.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 4: B (n=5,1,4,3) | 0.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 4: A (n=5,1,4,3) | 100.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 2: C (n=6,1,6,4) | 0.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Final Visit: D (n=3,1,5,2) | 0.0 percentage of participants |
| Pertuzumab 840 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Final Visit: C (n=3,1,5,2) | 0.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 4: D (n=5,1,4,3) | 0.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 2: A (n=6,1,6,4) | 100.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 2: B (n=6,1,6,4) | 0.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 2: C (n=6,1,6,4) | 0.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 2: D (n=6,1,6,4) | 0.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 4: A (n=5,1,4,3) | 75.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 4: B (n=5,1,4,3) | 25.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 4: C (n=5,1,4,3) | 0.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Final Visit: A (n=3,1,5,2) | 80.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Final Visit: B (n=3,1,5,2) | 0.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Final Visit: C (n=3,1,5,2) | 0.0 percentage of participants |
| Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Final Visit: D (n=3,1,5,2) | 20.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 4: B (n=5,1,4,3) | 0.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 4: A (n=5,1,4,3) | 100.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 2: A (n=6,1,6,4) | 100.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Final Visit: B (n=3,1,5,2) | 0.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 2: D (n=6,1,6,4) | 0.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 2: C (n=6,1,6,4) | 0.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Final Visit: D (n=3,1,5,2) | 0.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Final Visit: C (n=3,1,5,2) | 0.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 4: D (n=5,1,4,3) | 0.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 4: C (n=5,1,4,3) | 0.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Cycle 2: B (n=6,1,6,4) | 0.0 percentage of participants |
| Docetaxel 100 + Pertuzumab 420 | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Final Visit: A (n=3,1,5,2) | 100.0 percentage of participants |
Secondary
Plasma Decay Half Life (t1/2) for Pertuzumab in Combination With Docetaxel
The biological half-life or terminal half-life of pertuzumab is the time in days it takes for it to lose half of its pharmacologic activity.
Time frame: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22
Population: ITT population; Participants in any cohort infused with the specified dose of pertuzumab were included in analysis. number (n) equals (=) number of participants analyzed at the specified timepoint for each arm, respectively.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Entire Study Population | Plasma Decay Half Life (t1/2) for Pertuzumab in Combination With Docetaxel | Cycle 1 (n=8,11,0) | 12.65 days |
| Entire Study Population | Plasma Decay Half Life (t1/2) for Pertuzumab in Combination With Docetaxel | Cycle 2 (n=7,0,10) | 19.02 days |
| Pertuzumab 840 | Plasma Decay Half Life (t1/2) for Pertuzumab in Combination With Docetaxel | Cycle 1 (n=8,11,0) | 11.65 days |
| Pertuzumab 840 | Plasma Decay Half Life (t1/2) for Pertuzumab in Combination With Docetaxel | Cycle 2 (n=7,0,10) | NA days |
| Pertuzumab 420 | Plasma Decay Half Life (t1/2) for Pertuzumab in Combination With Docetaxel | Cycle 1 (n=8,11,0) | NA days |
| Pertuzumab 420 | Plasma Decay Half Life (t1/2) for Pertuzumab in Combination With Docetaxel | Cycle 2 (n=7,0,10) | 18.46 days |
Secondary
t1/2 for Docetaxel Alone and in Combination With Pertuzumab
The biological half-life or terminal half-life of docetaxel is the time in hours it takes for it to lose half of its pharmacologic activity. Data for docetaxel alone arms were analyzed for the timepoints on Day 1 prior to the administration of pertuzumab. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1.
Time frame: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose
Population: ITT population; Data from Cohort 2 (docetaxel 75 mg/m\^2 and pertuzumab 1050 mg) were excluded because there were only 2 participant data. It was planned not to report PK data, if less than or equal to 2 participants were analyzed. n= number of participants analyzed at the specified cycle.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Entire Study Population | t1/2 for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2(n=0,6,0,6,0,4) | NA days |
| Entire Study Population | t1/2 for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | 17.7 days |
| Pertuzumab 840 | t1/2 for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2(n=0,6,0,6,0,4) | 19.7 days |
| Pertuzumab 840 | t1/2 for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | NA days |
| Pertuzumab 420 | t1/2 for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2(n=0,6,0,6,0,4) | NA days |
| Pertuzumab 420 | t1/2 for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | 12.0 days |
| Docetaxel 100 + Pertuzumab 420 | t1/2 for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | NA days |
| Docetaxel 100 + Pertuzumab 420 | t1/2 for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2(n=0,6,0,6,0,4) | 13.8 days |
| Docetaxel 100 Alone | t1/2 for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | 8.92 days |
| Docetaxel 100 Alone | t1/2 for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2(n=0,6,0,6,0,4) | NA days |
| Docetaxel 100 + Pertuzumab 420 | t1/2 for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | NA days |
| Docetaxel 100 + Pertuzumab 420 | t1/2 for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2(n=0,6,0,6,0,4) | 11.8 days |
Secondary
Tmax for Docetaxel Alone and in Combination With Pertuzumab
Tmax is defined as the time after administration of a drug when the maximum plasma concentration is reached; Data for docetaxel alone arms were analyzed for the timepoints on Day 1 prior to the administration of pertuzumab. When the rate of absorption equals the rate of elimination. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1.
Time frame: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose
Population: ITT population; Data from Cohort 2 (docetaxel 75 mg/m\^2 and pertuzumab 1050 mg) were excluded because there were only 2 participant data. It was planned not to report PK data, if less than or equal to 2 participants were analyzed. n= number of participants analyzed at the specified cycle.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Entire Study Population | Tmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | 0.50 days |
| Entire Study Population | Tmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | NA days |
| Pertuzumab 840 | Tmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | NA days |
| Pertuzumab 840 | Tmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | 0.90 days |
| Pertuzumab 420 | Tmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | 0.50 days |
| Pertuzumab 420 | Tmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | NA days |
| Docetaxel 100 + Pertuzumab 420 | Tmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | NA days |
| Docetaxel 100 + Pertuzumab 420 | Tmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | 0.90 days |
| Docetaxel 100 Alone | Tmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | 0.90 days |
| Docetaxel 100 Alone | Tmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | NA days |
| Docetaxel 100 + Pertuzumab 420 | Tmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | NA days |
| Docetaxel 100 + Pertuzumab 420 | Tmax for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | 0.70 days |
Secondary
Volume of Distribution (Vz) at Steady State of Pertuzumab in Combination With Docetaxel
The volume of distribution at steady state (Vz), also known as apparent volume of distribution, is a pharmacological, theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma.
Time frame: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22
Population: ITT population; Participants in any cohort infused with the specified dose of pertuzumab were included in analysis.~n = number of participants analyzed at the specified timepoint for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Entire Study Population | Volume of Distribution (Vz) at Steady State of Pertuzumab in Combination With Docetaxel | Cycle 2 (n=7,0,10) | 4672 mL | Standard Deviation 1221 |
| Entire Study Population | Volume of Distribution (Vz) at Steady State of Pertuzumab in Combination With Docetaxel | Cycle 1 (n=8,11,0) | 5214 mL | Standard Deviation 1386 |
| Pertuzumab 840 | Volume of Distribution (Vz) at Steady State of Pertuzumab in Combination With Docetaxel | Cycle 1 (n=8,11,0) | 5355 mL | Standard Deviation 1680 |
| Pertuzumab 840 | Volume of Distribution (Vz) at Steady State of Pertuzumab in Combination With Docetaxel | Cycle 2 (n=7,0,10) | NA mL | — |
| Pertuzumab 420 | Volume of Distribution (Vz) at Steady State of Pertuzumab in Combination With Docetaxel | Cycle 2 (n=7,0,10) | 4233 mL | Standard Deviation 1555 |
| Pertuzumab 420 | Volume of Distribution (Vz) at Steady State of Pertuzumab in Combination With Docetaxel | Cycle 1 (n=8,11,0) | NA mL | — |
Secondary
Vss for Docetaxel Alone and in Combination With Pertuzumab
The volume of distribution at steady state (Vss), also known as apparent volume of distribution, is a pharmacological, theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1.
Time frame: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose
Population: ITT population; Data from Cohort 2 (docetaxel 75 mg/m\^2 and pertuzumab 1050 mg) were excluded because there were only 2 participant data. It was planned not to report PK data, if less than or equal to 2 participants were analyzed. n= number of participants analyzed at the specified cycle.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Entire Study Population | Vss for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | 786981 mL/m^2 | Standard Deviation 218139 |
| Entire Study Population | Vss for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | NA mL/m^2 | — |
| Pertuzumab 840 | Vss for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | 1023569 mL/m^2 | Standard Deviation 335711 |
| Pertuzumab 840 | Vss for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | NA mL/m^2 | — |
| Pertuzumab 420 | Vss for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | NA mL/m^2 | — |
| Pertuzumab 420 | Vss for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | 410174 mL/m^2 | Standard Deviation 184216 |
| Docetaxel 100 + Pertuzumab 420 | Vss for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | NA mL/m^2 | — |
| Docetaxel 100 + Pertuzumab 420 | Vss for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | 566759 mL/m^2 | Standard Deviation 361946 |
| Docetaxel 100 Alone | Vss for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | 254233 mL/m^2 | Standard Deviation 85054 |
| Docetaxel 100 Alone | Vss for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | NA mL/m^2 | — |
| Docetaxel 100 + Pertuzumab 420 | Vss for Docetaxel Alone and in Combination With Pertuzumab | Cycle 2 (n=0,6,0,6,0,4) | 428863 mL/m^2 | Standard Deviation 283977 |
| Docetaxel 100 + Pertuzumab 420 | Vss for Docetaxel Alone and in Combination With Pertuzumab | Cycle 1 (n=6,0,6,0,5,0) | NA mL/m^2 | — |