Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Epirubicin

Epothilones

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Tubulin Modulators

Antimitotic Agents

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.

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.

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.

Infusion, intravenous (IV), Cycle = 21 days. Dose escalation study.

Ixabepilone

Infusion, intravenous (IV): 75 mg/m\^2. Cycle = 21 days, up to 10 cycles or cumulative dose of 800 mg/m².

Bristol-Myers Squibb

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.

Phase I Combination w/ Epirubicin

A Phase I Study of Ixabepilone in Combination With Epirubicin in Patients With Metastatic Breast Cancer

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

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

R-Pharm

Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2

Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2

Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2

Total

Between 18 and 65 years

>=65 years

Age, Customized

Age, Continuous

Sex: Female, Male

France

Italy

Region of Enrollment

BMS Study Director

Participants with DLT:Grade 4 (severe) neutropenia

Total Participants with DLT

Participants without DLT

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.

Number of Participants With a Dose Limiting Toxicity (DLT)

R2PD

All participants received Ixabepilone administered as a 3-hour IV infusion following a 3- to 5-minute IV infusion of Epirubicin every 21 days.

All Participants With Measurable Disease and Tumor Response

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.

Ixabepilone Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (R2PD)

Deaths (total)

Deaths within 30 days of last dose

SAEs

Grade 3/4 AEs

AEs leading to discontinuation of study treatment

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.

Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation

Participants who had received any treatment with ixabepilone and epirubicin and had adequate concentration profiles.

Maximum Plasma Concentration (Cmax) of Single-dose Ixabepilone

Area Under the Curve, Extrapolated to Infinity (AUC[INF]) of Single-dose Ixabepilone

Terminal Half-life (T-Half) of Single-dose Ixabepilone

Clearance (CLT) of Single-dose Ixabepilone

Volume of Distribution at Steady State (Vss) of Single-dose Ixabepilone

Epirubicin Cmax

Epirubicin AUC(INF)

Epirubicin T-Half

Epirubicin CLT

Epirubicin Vss

Complete Response

Partial Response

Stable Disease

Progressive Disease

Participants with measurable disease at baseline per RECIST

All Participants With Measurable Disease

Participants treated at the MTD with measurable disease at baseline per RECIST

All Response-evaluable Participants

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.

Number Of Participants With A Best Overall Tumor Response of Complete Response, Partial Response, Stable Disease, And Progressive Disease

All participants with measurable disease and with a best tumor response of either CR or PR.

Spots Global Cancer Trial Database for Phase I Combination w/ Epirubicin

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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