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Phase I Combination w/ Epirubicin

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00322374
First received: May 1, 2006
Last updated: April 21, 2011
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Metastatic Breast Cancer
Drug: Ixabepilone
Drug: Epirubicin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Ixabepilone in Combination With Epirubicin in Patients With Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Number of Participants With a Dose Limiting Toxicity (DLT) [ Time Frame: From Baseline to the end of Cycle 1 (Day 21) ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Day 21 of Cycle 1 ] [ Designated as safety issue: Yes ]
    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 Outcome Measures:
  • Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation [ Time Frame: Evaluated continuously on study from Baseline to ≤30 days after the last dose of study drug. ] [ Designated as safety issue: Yes ]
    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

  • Maximum Plasma Concentration (Cmax) of Single-dose Ixabepilone [ Time Frame: From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion. ] [ Designated as safety issue: No ]
    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.

  • Area Under the Curve, Extrapolated to Infinity (AUC[INF]) of Single-dose Ixabepilone [ Time Frame: From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion. ] [ Designated as safety issue: No ]
    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 [ Time Frame: From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion. ] [ Designated as safety issue: No ]
    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 [ Time Frame: From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion. ] [ Designated as safety issue: No ]
    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 [ Time Frame: From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion. ] [ Designated as safety issue: No ]
    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 [ Time Frame: From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion. ] [ Designated as safety issue: No ]
    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) [ Time Frame: From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion. ] [ Designated as safety issue: No ]
    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.

  • Epirubicin T-Half [ Time Frame: From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion. ] [ Designated as safety issue: No ]
    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.

  • Epirubicin CLT [ Time Frame: From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion. ] [ Designated as safety issue: No ]
    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 [ Time Frame: From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion. ] [ Designated as safety issue: No ]
    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 [ Time Frame: From Baseline (up to 2 weeks prior to starting therapy) to the end Cycle 2 ] [ Designated as safety issue: No ]
    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 Frame: Time (in months) when criteria for CR or PR are met (which ever occurs first) up to date of progressive disease. ] [ Designated as safety issue: No ]
    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 Frame: Time (in months) when criteria for CR or PR are met (which ever occurs first) up to date of progressive disease. ] [ Designated as safety issue: No ]
    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.


Enrollment: 42
Study Start Date: August 2006
Study Completion Date: February 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 25 mg/m^2 Ixabepilone plus 75 mg/m^2 Epirubicin
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.
Drug: Ixabepilone
Infusion, intravenous (IV), Cycle = 21 days. Dose escalation study.
Other Names:
  • IXEMPRA®
  • BMS-247550
  • Epothilone
Drug: Epirubicin
Infusion, intravenous (IV): 75 mg/m^2. Cycle = 21 days, up to 10 cycles or cumulative dose of 800 mg/m².
Experimental: 30 mg/m^2 Ixabepilone plus 75 mg/m^2 Epirubicin
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.
Drug: Ixabepilone
Infusion, intravenous (IV), Cycle = 21 days. Dose escalation study.
Other Names:
  • IXEMPRA®
  • BMS-247550
  • Epothilone
Drug: Epirubicin
Infusion, intravenous (IV): 75 mg/m^2. Cycle = 21 days, up to 10 cycles or cumulative dose of 800 mg/m².
Experimental: 35 mg/m^2 Ixabepilone plus 75 mg/m^2 Epirubicin
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.
Drug: Ixabepilone
Infusion, intravenous (IV), Cycle = 21 days. Dose escalation study.
Other Names:
  • IXEMPRA®
  • BMS-247550
  • Epothilone
Drug: Epirubicin
Infusion, intravenous (IV): 75 mg/m^2. Cycle = 21 days, up to 10 cycles or cumulative dose of 800 mg/m².

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00322374

Locations
France
Local Institution
Toulouse Cedex 3, France, 31052
Italy
Local Institution
Milano, Italy, 20133
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00322374     History of Changes
Other Study ID Numbers: CA163-104, Eudract No: 2005-004864-22
Study First Received: May 1, 2006
Results First Received: July 6, 2010
Last Updated: April 21, 2011
Health Authority: Italy:Commissario Straordinario dell' Istituto Nazionale per lo Studio e la Cura dei Tumori

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Epirubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 20, 2014