Phase I Combination w/ Epirubicin

Metastatic Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00322374
• Other study ID #: CA163-104
• Secondary ID: Eudract No: 2005
• Status: Completed
• Phase: Phase 1
• First received: May 1, 2006
• Last updated: February 9, 2016
• Start date: August 2006
• Est. completion date: February 2009

Study information

• Verified date: February 2016
• Source: R-Pharm
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy:Commissario Straordinario dell' Istituto Nazionale per lo Studio e la Cura dei Tumori
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: February 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Metastatic Breast Cancer

Intervention

Drug:
• Ixabepilone
Infusion, intravenous (IV), Cycle = 21 days. Dose escalation study.
• Epirubicin
Infusion, intravenous (IV): 75 mg/m^2. Cycle = 21 days, up to 10 cycles or cumulative dose of 800 mg/m².

Locations

Country	Name	City	State
France	Local Institution	Toulouse Cedex 3
Italy	Local Institution	Milano

Sponsors (1)

Lead Sponsor	Collaborator
R-Pharm

Countries where clinical trial is conducted

France,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	From Baseline to the end of Cycle 1 (Day 21)	Yes
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.	Day 21 of Cycle 1	Yes
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	Evaluated continuously on study from Baseline to =30 days after the last dose of study drug.	Yes
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.	From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion.	No
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.	From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion.	No
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.	From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion.	No
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.	From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion.	No
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.	From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion.	No
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.	From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion.	No
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.	From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion.	No
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.	From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion.	No
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.	From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion.	No
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.	From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion.	No
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.	From Baseline (up to 2 weeks prior to starting therapy) to the end Cycle 2	No
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 (in months) when criteria for CR or PR are met (which ever occurs first) up to date of progressive disease.	No
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 (in months) when criteria for CR or PR are met (which ever occurs first) up to date of progressive disease.	No

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