Metastatic Breast Cancer
Conditions
Brief summary
Tumor response information was obtained for all participants who received at least 2 cycles of study drug, underwent requisite baseline and on-treatment disease assessments and had at least one post-treatment assessment. Tumor response assessment in evaluable participants was done according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
Interventions
DRUGIxabepilone
Infusion, intravenous (IV), Cycle = 21 days. Dose escalation study.
DRUGEpirubicin
Infusion, intravenous (IV): 75 mg/m\^2. Cycle = 21 days, up to 10 cycles or cumulative dose of 800 mg/m².
Sponsors
R-Pharm
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women ≥18 years * Histologically or cytologically confirmed diagnosis of metastatic breast cancer * Measurable or nonmeasurable disease defined by Response Evaluation Criteria In Solid Tumors (RECIST)
Exclusion criteria
* Number of prior chemotherapy lines of treatment in the metastatic setting ≥2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Dose Limiting Toxicity (DLT) | From Baseline to the end of Cycle 1 (Day 21) | DLT: any of the following considered related to ixabepilone, epirubicin or combination occurring in Cycle 1: Absolute neutrophil count \<500 cells/mm\^3 for ≥7 consecutive days or febrile neutropenia of any duration;Grade(Gr)4 thrombocytopenia \<25,000 cells/mm\^3 or Gr3 w/bleeding requiring platelet transfusion;Any other drug-related Gr3/4 non-hematologic toxicity except Gr3 injection site reaction, fatigue, transient arthralgia/myalgia;Delayed recovery to Gr≤1 or baseline (except for alopecia) from toxicity related to treatment w/ ixabepilone + epirubicin delaying initiation of next cycle ≥3 wks |
| Ixabepilone Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (R2PD) | Day 21 of Cycle 1 | The MTD was the highest dose in which 0/6 or 1/6 participants experienced DLT with at least 2 out of no more than 6 participants experiencing DLT at the next higher dose level. The RP2D was based on the MTD and the assessment of any relevant chronic toxicity. To obtain further confidence in the RP2D, a total maximum of 30 evaluable participants were enrolled at the MTD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve, Extrapolated to Infinity (AUC[INF]) of Single-dose Ixabepilone | From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion. | PK is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. AUC(INF)=area under the plasma concentration-time curve from time zero extrapolated to infinite time of single-dose ixabepilone administered with IV dose of epirubicin 75 mg/m\^2. |
| Terminal Half-life (T-Half) of Single-dose Ixabepilone | From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion. | PK is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. T-Half=terminal-phase elimination half-life in plasma of single-dose ixabepilone administered with IV dose of epirubicin 75 mg/m\^2, derived from plasma concentration versus time data. |
| Clearance (CLT) of Single-dose Ixabepilone | From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion. | PK is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. CLT= Total body clearance from plasma of single-dose ixabepilone administered with IV dose of epirubicin 75 mg/m\^2, derived from plasma concentration versus time data. |
| Volume of Distribution at Steady State (Vss) of Single-dose Ixabepilone | From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion. | PK is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. Vss= Volume of distribution at steady-state of single-dose ixabepilone administered with IV dose of epirubicin 75 mg/m\^2, derived from plasma concentration versus time data. |
| Epirubicin Cmax | From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion. | PK is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. Cmax=maximum observed plasma concentration of epirubicin administered IV 75 mg/m\^2, derived from plasma concentration versus time data. |
| Epirubicin AUC(INF) | From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion. | PK is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. AUC(INF)=the area under the plasma concentration-time curve from time zero extrapolated to infinity of epirubicin administered IV 75 mg/m\^2, derived from plasma concentration versus time data. |
| Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation | Evaluated continuously on study from Baseline to ≤30 days after the last dose of study drug. | AEs and SAEs considered possibly, probably, or certainly related to study treatment, graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death).SAE= any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization/prolongation of existing hospitalization, results in persistent/significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event |
| Epirubicin CLT | From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion. | PK is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. CLT= Total body clearance from plasma of epirubicin administered IV 75 mg/m\^2, derived from plasma concentration versus time data. |
| Epirubicin Vss | From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion. | PK is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. Vss= Volume of distribution at steady-state of epirubicin administered IV 75 mg/m\^2, derived from plasma concentration versus time data. |
| Number Of Participants With A Best Overall Tumor Response of Complete Response, Partial Response, Stable Disease, And Progressive Disease | From Baseline (up to 2 weeks prior to starting therapy) to the end Cycle 2 | Information on all tumor lesions was obtained at baseline by radiologic techniques, or if appropriate by physical examination (e.g. subcutaneous nodules). Measurable tumors were evaluated using Response Evaluation Criteria In Solid Tumors (RECIST) criteria, wherein complete response (CR) = disappearance of all target lesions; partial response (PR) = ≥30% decrease in the sum of the longest diameter of target lesions; progressive disease (PD)= ≥20% increase in the sum of the longest diameter of target lesions, and stable disease (SD) = small changes that do not meet above criteria. |
| Duration of Tumor Response | Time (in months) when criteria for CR or PR are met (which ever occurs first) up to date of progressive disease. | Defined as the interval measured from the time that the measurement criteria are first met for CR or PR, whichever occurs first, until the date of documented progressive disease or death. CR= disappearance of all target lesions; PR= ≥30% decrease in the sum of the longest diameter of target lesions. |
| Number Of Participants With Tumor Response by Duration of Response Category | Time (in months) when criteria for CR or PR are met (which ever occurs first) up to date of progressive disease. | Duration of response was defined as the interval measured from the time that the measurement criteria are first met for CR or PR, whichever occurs first, until the date of documented progressive disease or death; PR= ≥30% decrease in the sum of the longest diameter of target lesions. |
| Epirubicin T-Half | From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion. | PK is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. T-Half=terminal-phase elimination half-life in plasma of epirubicin administered IV dose 75 mg/m\^2, derived from plasma concentration versus time data. |
| Maximum Plasma Concentration (Cmax) of Single-dose Ixabepilone | From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion. | Pharmacokinetics (PK) is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. Cmax=maximum observed plasma concentration of single-dose ixabepilone administered with IV dose of epirubicin 75 mg/m\^2, derived from plasma concentration versus time data. |
Countries
France, Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 Participants received 25 mg/m\^2 Ixabepilone as a 3-hour IV infusion following a 3- to 5-minute IV infusion of 75 mg/m\^2 epirubicin every 21 days. | 6 |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 Participants received 30 mg/m\^2 Ixabepilone as a 3-hour IV infusion following a 3- to 5-minute IV infusion of 75 mg/m\^2 epirubicin every 21 days. | 30 |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 Participants received 35 mg/m\^2 Ixabepilone as a 3-hour IV infusion following a 3- to 5-minute IV infusion of 75 mg/m\^2 epirubicin every 21 days. | 6 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| First Escalation | Documented Disease Progression | 0 | 6 | 0 | 0 |
| First Escalation | Participant Request | 0 | 1 | 0 | 0 |
| First Escalation | Physician Decision | 0 | 12 | 0 | 0 |
| First Escalation | Study Drug Toxicity | 0 | 11 | 0 | 0 |
| Second Escalation | Physician Decision | 0 | 0 | 5 | 0 |
| Second Escalation | Study Drug Toxicity | 0 | 0 | 1 | 0 |
| Starting Dose | Physician Decision | 2 | 0 | 0 | 0 |
| Starting Dose | Study Drug Toxicity | 4 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | Total | Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 |
|---|---|---|---|---|
| Age, Continuous | 53.5 years | 57 years | 57.5 years | 57.5 years |
| Age, Customized >=65 years | 1 participants | 7 participants | 0 participants | 6 participants |
| Age, Customized Between 18 and 65 years | 5 participants | 35 participants | 6 participants | 24 participants |
| Region of Enrollment France | 3 participants | 24 participants | 5 participants | 16 participants |
| Region of Enrollment Italy | 3 participants | 18 participants | 1 participants | 14 participants |
| Sex: Female, Male Female | 6 Participants | 42 Participants | 6 Participants | 30 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 30 / 30 | 6 / 6 |
| serious Total, serious adverse events | 2 / 6 | 8 / 30 | 1 / 6 |
Outcome results
Primary
Ixabepilone Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (R2PD)
The MTD was the highest dose in which 0/6 or 1/6 participants experienced DLT with at least 2 out of no more than 6 participants experiencing DLT at the next higher dose level. The RP2D was based on the MTD and the assessment of any relevant chronic toxicity. To obtain further confidence in the RP2D, a total maximum of 30 evaluable participants were enrolled at the MTD.
Time frame: Day 21 of Cycle 1
Population: The evaluable participant population consisted of participants who met the minimum safety evaluation requirements of the study: participant received ≥1 dose of ixabepilone and epirubicin in Cycle 1, completed adequate safety evaluations, and were observed for ≥21 days following the first dose or the participant experienced DLT.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (R2PD) | R2PD | 30 mg^m2 |
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (R2PD) | MTD | 30 mg^m2 |
Primary
Number of Participants With a Dose Limiting Toxicity (DLT)
DLT: any of the following considered related to ixabepilone, epirubicin or combination occurring in Cycle 1: Absolute neutrophil count \<500 cells/mm\^3 for ≥7 consecutive days or febrile neutropenia of any duration;Grade(Gr)4 thrombocytopenia \<25,000 cells/mm\^3 or Gr3 w/bleeding requiring platelet transfusion;Any other drug-related Gr3/4 non-hematologic toxicity except Gr3 injection site reaction, fatigue, transient arthralgia/myalgia;Delayed recovery to Gr≤1 or baseline (except for alopecia) from toxicity related to treatment w/ ixabepilone + epirubicin delaying initiation of next cycle ≥3 wks
Time frame: From Baseline to the end of Cycle 1 (Day 21)
Population: The evaluable participant population consisted of participants who met the minimum safety evaluation requirements of the study: participant received ≥1 dose of ixabepilone and epirubicin in Cycle 1, completed adequate safety evaluations, and was observed for ≥21 days following the first dose or the participant experienced DLT.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With a Dose Limiting Toxicity (DLT) | Total Participants with DLT | 1 Participants |
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With a Dose Limiting Toxicity (DLT) | Participants with DLT:Grade 4 (severe) neutropenia | 1 Participants |
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With a Dose Limiting Toxicity (DLT) | Participants without DLT | 5 Participants |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With a Dose Limiting Toxicity (DLT) | Total Participants with DLT | 1 Participants |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With a Dose Limiting Toxicity (DLT) | Participants with DLT:Grade 4 (severe) neutropenia | 1 Participants |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With a Dose Limiting Toxicity (DLT) | Participants without DLT | 5 Participants |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With a Dose Limiting Toxicity (DLT) | Participants with DLT:Grade 4 (severe) neutropenia | 2 Participants |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With a Dose Limiting Toxicity (DLT) | Participants without DLT | 4 Participants |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With a Dose Limiting Toxicity (DLT) | Total Participants with DLT | 2 Participants |
Secondary
Area Under the Curve, Extrapolated to Infinity (AUC[INF]) of Single-dose Ixabepilone
PK is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. AUC(INF)=area under the plasma concentration-time curve from time zero extrapolated to infinite time of single-dose ixabepilone administered with IV dose of epirubicin 75 mg/m\^2.
Time frame: From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion.
Population: Participants who had received any treatment with ixabepilone and epirubicin and had adequate concentration profiles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Area Under the Curve, Extrapolated to Infinity (AUC[INF]) of Single-dose Ixabepilone | 1760.42 ng·h/mL | Standard Deviation 535.89 |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Area Under the Curve, Extrapolated to Infinity (AUC[INF]) of Single-dose Ixabepilone | 2072.43 ng·h/mL | Standard Deviation 399.6 |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | Area Under the Curve, Extrapolated to Infinity (AUC[INF]) of Single-dose Ixabepilone | 2100.56 ng·h/mL | Standard Deviation 353.87 |
Secondary
Clearance (CLT) of Single-dose Ixabepilone
PK is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. CLT= Total body clearance from plasma of single-dose ixabepilone administered with IV dose of epirubicin 75 mg/m\^2, derived from plasma concentration versus time data.
Time frame: From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion.
Population: Participants who had received any treatment with ixabepilone and epirubicin and had adequate concentration profiles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Clearance (CLT) of Single-dose Ixabepilone | 26.03 L/h | Standard Deviation 5.45 |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Clearance (CLT) of Single-dose Ixabepilone | 24.62 L/h | Standard Deviation 5.56 |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | Clearance (CLT) of Single-dose Ixabepilone | 26.68 L/h | Standard Deviation 2.83 |
Secondary
Duration of Tumor Response
Defined as the interval measured from the time that the measurement criteria are first met for CR or PR, whichever occurs first, until the date of documented progressive disease or death. CR= disappearance of all target lesions; PR= ≥30% decrease in the sum of the longest diameter of target lesions.
Time frame: Time (in months) when criteria for CR or PR are met (which ever occurs first) up to date of progressive disease.
Population: Participants with measurable disease who received any treatment, as well as response evaluable participants. Evaluations were based on tumor measurements collected on the case report form using RECIST incorporating the use of target/non-target lesions.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Duration of Tumor Response | 6.45 months |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Duration of Tumor Response | 6.4 months |
Secondary
Epirubicin AUC(INF)
PK is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. AUC(INF)=the area under the plasma concentration-time curve from time zero extrapolated to infinity of epirubicin administered IV 75 mg/m\^2, derived from plasma concentration versus time data.
Time frame: From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion.
Population: Participants who had received any treatment with ixabepilone and epirubicin and had adequate concentration profiles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Epirubicin AUC(INF) | 2489.37 ng·h/mL | Standard Deviation 1488.39 |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Epirubicin AUC(INF) | 3132.67 ng·h/mL | Standard Deviation 1685.32 |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | Epirubicin AUC(INF) | 2595.44 ng·h/mL | Standard Deviation 1017.64 |
Secondary
Epirubicin CLT
PK is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. CLT= Total body clearance from plasma of epirubicin administered IV 75 mg/m\^2, derived from plasma concentration versus time data.
Time frame: From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion.
Population: Participants who had received any treatment with ixabepilone and epirubicin and had adequate concentration profiles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Epirubicin CLT | 81.33 L/h | Standard Deviation 70.84 |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Epirubicin CLT | 53.85 L/h | Standard Deviation 32.87 |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | Epirubicin CLT | 58.00 L/h | Standard Deviation 38.82 |
Secondary
Epirubicin Cmax
PK is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. Cmax=maximum observed plasma concentration of epirubicin administered IV 75 mg/m\^2, derived from plasma concentration versus time data.
Time frame: From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion.
Population: Participants who had received any treatment with ixabepilone and epirubicin and had adequate concentration profiles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Epirubicin Cmax | 3306.53 ng/ml | Standard Deviation 2125.45 |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Epirubicin Cmax | 4139.00 ng/ml | Standard Deviation 2598.19 |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | Epirubicin Cmax | 4533.08 ng/ml | Standard Deviation 2490.83 |
Secondary
Epirubicin T-Half
PK is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. T-Half=terminal-phase elimination half-life in plasma of epirubicin administered IV dose 75 mg/m\^2, derived from plasma concentration versus time data.
Time frame: From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion.
Population: Participants who had received any treatment with ixabepilone and epirubicin and had adequate concentration profiles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Epirubicin T-Half | 13.61 hours | Standard Deviation 3.33 |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Epirubicin T-Half | 19.41 hours | Standard Deviation 6.31 |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | Epirubicin T-Half | 15.55 hours | Standard Deviation 2.92 |
Secondary
Epirubicin Vss
PK is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. Vss= Volume of distribution at steady-state of epirubicin administered IV 75 mg/m\^2, derived from plasma concentration versus time data.
Time frame: From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion.
Population: Participants who had received any treatment with ixabepilone and epirubicin and had adequate concentration profiles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Epirubicin Vss | 912.83 liters | Standard Deviation 1500.018 |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Epirubicin Vss | 750.24 liters | Standard Deviation 977.352 |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | Epirubicin Vss | 522.45 liters | Standard Deviation 657.97 |
Secondary
Maximum Plasma Concentration (Cmax) of Single-dose Ixabepilone
Pharmacokinetics (PK) is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. Cmax=maximum observed plasma concentration of single-dose ixabepilone administered with IV dose of epirubicin 75 mg/m\^2, derived from plasma concentration versus time data.
Time frame: From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion.
Population: Participants who had received any treatment with ixabepilone and epirubicin and had adequate concentration profiles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Maximum Plasma Concentration (Cmax) of Single-dose Ixabepilone | 169.00 ng/ml | Standard Deviation 44.42 |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Maximum Plasma Concentration (Cmax) of Single-dose Ixabepilone | 217.86 ng/ml | Standard Deviation 53.56 |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | Maximum Plasma Concentration (Cmax) of Single-dose Ixabepilone | 251.83 ng/ml | Standard Deviation 48.56 |
Secondary
Number Of Participants With A Best Overall Tumor Response of Complete Response, Partial Response, Stable Disease, And Progressive Disease
Information on all tumor lesions was obtained at baseline by radiologic techniques, or if appropriate by physical examination (e.g. subcutaneous nodules). Measurable tumors were evaluated using Response Evaluation Criteria In Solid Tumors (RECIST) criteria, wherein complete response (CR) = disappearance of all target lesions; partial response (PR) = ≥30% decrease in the sum of the longest diameter of target lesions; progressive disease (PD)= ≥20% increase in the sum of the longest diameter of target lesions, and stable disease (SD) = small changes that do not meet above criteria.
Time frame: From Baseline (up to 2 weeks prior to starting therapy) to the end Cycle 2
Population: Participants with measurable disease who received any treatment, as well as response evaluable participants. Evaluations were based on tumor measurements collected on the case report form using RECIST incorporating the use of target/non-target lesions.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Number Of Participants With A Best Overall Tumor Response of Complete Response, Partial Response, Stable Disease, And Progressive Disease | Complete Response | 0 participants |
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Number Of Participants With A Best Overall Tumor Response of Complete Response, Partial Response, Stable Disease, And Progressive Disease | Partial Response | 18 participants |
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Number Of Participants With A Best Overall Tumor Response of Complete Response, Partial Response, Stable Disease, And Progressive Disease | Stable Disease | 11 participants |
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Number Of Participants With A Best Overall Tumor Response of Complete Response, Partial Response, Stable Disease, And Progressive Disease | Progressive Disease | 3 participants |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Number Of Participants With A Best Overall Tumor Response of Complete Response, Partial Response, Stable Disease, And Progressive Disease | Progressive Disease | 3 participants |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Number Of Participants With A Best Overall Tumor Response of Complete Response, Partial Response, Stable Disease, And Progressive Disease | Complete Response | 0 participants |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Number Of Participants With A Best Overall Tumor Response of Complete Response, Partial Response, Stable Disease, And Progressive Disease | Stable Disease | 10 participants |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Number Of Participants With A Best Overall Tumor Response of Complete Response, Partial Response, Stable Disease, And Progressive Disease | Partial Response | 9 participants |
Secondary
Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation
AEs and SAEs considered possibly, probably, or certainly related to study treatment, graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death).SAE= any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization/prolongation of existing hospitalization, results in persistent/significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event
Time frame: Evaluated continuously on study from Baseline to ≤30 days after the last dose of study drug.
Population: All participants who received at least 1 cycle of therapy were evaluable for safety; adverse events and other symptoms were graded according to CTCAE Version 3.0.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation | Deaths (total) | 0 participants |
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation | Deaths within 30 days of last dose | 0 participants |
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation | AEs | 6 participants |
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation | SAEs | 2 participants |
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation | Grade 3/4 AEs | 6 participants |
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation | AEs leading to discontinuation of study treatment | 4 participants |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation | AEs leading to discontinuation of study treatment | 12 participants |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation | Deaths (total) | 0 participants |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation | SAEs | 8 participants |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation | Grade 3/4 AEs | 28 participants |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation | Deaths within 30 days of last dose | 0 participants |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation | AEs | 30 participants |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation | Deaths within 30 days of last dose | 0 participants |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation | AEs | 6 participants |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation | AEs leading to discontinuation of study treatment | 1 participants |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation | SAEs | 1 participants |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation | Deaths (total) | 0 participants |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation | Grade 3/4 AEs | 6 participants |
Secondary
Number Of Participants With Tumor Response by Duration of Response Category
Duration of response was defined as the interval measured from the time that the measurement criteria are first met for CR or PR, whichever occurs first, until the date of documented progressive disease or death; PR= ≥30% decrease in the sum of the longest diameter of target lesions.
Time frame: Time (in months) when criteria for CR or PR are met (which ever occurs first) up to date of progressive disease.
Population: Participants with measurable disease who received any treatment, as well as response evaluable participants. Evaluations were based on tumor measurements collected on the case report form using RECIST incorporating the use of target/non-target lesions.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Number Of Participants With Tumor Response by Duration of Response Category | Response Duration ≥4 Months | 13 participants |
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Number Of Participants With Tumor Response by Duration of Response Category | Response Duration < 4 Months | 5 participants |
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Number Of Participants With Tumor Response by Duration of Response Category | Response Duration ≥6 Months | 11 participants |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Number Of Participants With Tumor Response by Duration of Response Category | Response Duration < 4 Months | 1 participants |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Number Of Participants With Tumor Response by Duration of Response Category | Response Duration ≥4 Months | 8 participants |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Number Of Participants With Tumor Response by Duration of Response Category | Response Duration ≥6 Months | 6 participants |
Secondary
Terminal Half-life (T-Half) of Single-dose Ixabepilone
PK is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. T-Half=terminal-phase elimination half-life in plasma of single-dose ixabepilone administered with IV dose of epirubicin 75 mg/m\^2, derived from plasma concentration versus time data.
Time frame: From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion.
Population: Participants who had received any treatment with ixabepilone and epirubicin and had adequate concentration profiles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Terminal Half-life (T-Half) of Single-dose Ixabepilone | 51.82 hours | Standard Deviation 15.47 |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Terminal Half-life (T-Half) of Single-dose Ixabepilone | 34.07 hours | Standard Deviation 11.75 |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | Terminal Half-life (T-Half) of Single-dose Ixabepilone | 44.15 hours | Standard Deviation 18.41 |
Secondary
Volume of Distribution at Steady State (Vss) of Single-dose Ixabepilone
PK is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. Vss= Volume of distribution at steady-state of single-dose ixabepilone administered with IV dose of epirubicin 75 mg/m\^2, derived from plasma concentration versus time data.
Time frame: From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion.
Population: Participants who had received any treatment with ixabepilone and epirubicin and had adequate concentration profiles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Volume of Distribution at Steady State (Vss) of Single-dose Ixabepilone | 1331.65 liters | Standard Deviation 370.88 |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Volume of Distribution at Steady State (Vss) of Single-dose Ixabepilone | 803.21 liters | Standard Deviation 292.09 |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | Volume of Distribution at Steady State (Vss) of Single-dose Ixabepilone | 1001.70 liters | Standard Deviation 317.23 |