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

History of Changes

Results First Received: July 6, 2010

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Single Group Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Metastatic Breast Cancer
Interventions:	Drug: Ixabepilone Drug: Epirubicin

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
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.
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.
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.
All Participants	No text entered.

Participant Flow for 4 periods

Period 1: Enrollment

	Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2	All Participants
STARTED	0	0	0	42
COMPLETED	0	0	0	42
NOT COMPLETED	0	0	0	0

Period 2: Starting Dose

	Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2	All Participants
STARTED	6	0	0	0
COMPLETED	0	0	0	0
NOT COMPLETED	6	0	0	0
Documented Disease Progression	0	0	0	0
Physician Decision	2	0	0	0
Study Drug Toxicity	4	0	0	0
Participant Request	0	0	0	0

Period 3: First Escalation

	Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2	All Participants
STARTED	0	30	0	0
COMPLETED	0	0	0	0
NOT COMPLETED	0	30	0	0
Documented Disease Progression	0	6	0	0
Physician Decision	0	12	0	0
Study Drug Toxicity	0	11	0	0
Participant Request	0	1	0	0

Period 4: Second Escalation

	Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2	All Participants
STARTED	0	0	6	0
COMPLETED	0	0	0	0
NOT COMPLETED	0	0	6	0
Physician Decision	0	0	5	0
Study Drug Toxicity	0	0	1	0

Baseline Characteristics

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Reporting Groups

	Description
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.
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.
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.
Total	Total of all reporting groups

Baseline Measures

	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
Number of Participants [units: participants]	6	30	6	42
Age, Customized [units: participants]
Between 18 and 65 years	6	24	5	35
>=65 years	0	6	1	7
Age [units: years] Median ( Full Range )	57.5 ( 48 to 61 )	57.5 ( 38 to 69 )	53.5 ( 33 to 68 )	57 ( 33 to 69 )
Gender [units: participants]
Female	6	30	6	42
Male	0	0	0	0
Region of Enrollment [units: participants]
France	5	16	3	24
Italy	1	14	3	18

Outcome Measures

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1. Primary:

Number of Participants With a Dose Limiting Toxicity (DLT) [ Time Frame: From Baseline to the end of Cycle 1 (Day 21) ]

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2. Primary:

Ixabepilone Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (R2PD) [ Time Frame: Day 21 of Cycle 1 ]

Show Outcome Measure 2

3. Secondary:

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. ]

Show Outcome Measure 3

4. Secondary:

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. ]

Show Outcome Measure 4

5. Secondary:

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. ]

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6. Secondary:

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. ]

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7. Secondary:

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. ]

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8. Secondary:

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. ]

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9. Secondary:

Epirubicin Cmax [ Time Frame: From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion. ]

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Measure Type	Secondary
Measure Title	Epirubicin Cmax
Measure Description	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.
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who had received any treatment with ixabepilone and epirubicin and had adequate concentration profiles.

Reporting Groups

	Description
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.
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.
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.

Measured Values

	Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2
Number of Participants Analyzed [units: participants]	6	28	6
Epirubicin Cmax [units: ng/ml] Mean ± Standard Deviation	3306.53 ± 2125.45	4139.00 ± 2598.19	4533.08 ± 2490.83

No statistical analysis provided for Epirubicin Cmax

10. Secondary:

Epirubicin AUC(INF) [ Time Frame: From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion. ]

Show Outcome Measure 10

11. Secondary:

Epirubicin T-Half [ Time Frame: From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion. ]

Show Outcome Measure 11

12. Secondary:

Epirubicin CLT [ Time Frame: From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion. ]

Show Outcome Measure 12

13. Secondary:

Epirubicin Vss [ Time Frame: From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion. ]

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14. Secondary:

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 ]

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15. Secondary:

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. ]

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16. Secondary:

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. ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com

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

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