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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Infusion, intravenous (IV), Cycle = 21 days. Dose escalation study.
Infusion, intravenous (IV): 75 mg/m\^2. Cycle = 21 days, up to 10 cycles or cumulative dose of 800 mg/m².
Local Institution
Toulouse, France
Local Institution
Milan, Italy
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)
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
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.
Maximum Plasma Concentration (Cmax) of Single-dose Ixabepilone
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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.
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.