Phase I Combination w/ Epirubicin

• Sponsor: R-Pharm (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00322374
• Collaborator: (none)
• Enrollment: 42
• Locations: 2
• Arms: 3
• Duration (Months): 30.1
• Patients Per Site: 21
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: Ixabepilone; Drug: Epirubicin	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Study of Ixabepilone in Combination With Epirubicin in Patients With Metastatic Breast Cancer
• Study Start Date: Aug 1, 2006
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
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.

Outcome Measures

Primary Outcome Measures

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

   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

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

   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

1. Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation [Evaluated continuously on study from Baseline to ≤30 days after the last dose of study drug.]

   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

2. Maximum Plasma Concentration (Cmax) of Single-dose Ixabepilone [From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion.]

   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.

3. Area Under the Curve, Extrapolated to Infinity (AUC[INF]) of Single-dose Ixabepilone [From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion.]

   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.

4. Terminal Half-life (T-Half) of Single-dose Ixabepilone [From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion.]

   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.

5. Clearance (CLT) of Single-dose Ixabepilone [From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion.]

   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.

6. Volume of Distribution at Steady State (Vss) of Single-dose Ixabepilone [From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion.]

   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.

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

   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.

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

   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.

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

   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.

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

    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.

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

    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.

12. Number Of Participants With A Best Overall Tumor Response of Complete Response, Partial Response, Stable Disease, And Progressive Disease [From Baseline (up to 2 weeks prior to starting therapy) to the end Cycle 2]

    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.

13. Duration of Tumor Response [Time (in months) when criteria for CR or PR are met (which ever occurs first) up to date of progressive disease.]

    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.

14. Number Of Participants With Tumor Response by Duration of Response Category [Time (in months) when criteria for CR or PR are met (which ever occurs first) up to date of progressive disease.]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Local Institution	Toulouse Cedex 3		France	31052
2	Local Institution	Milano		Italy	20133

Sponsors and Collaborators

• R-Pharm

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: R-Pharm
• ClinicalTrials.gov Identifier: NCT00322374
• Other Study ID Numbers: CA163-104; Eudract No: 2005-004864-22
• First Posted: May 5, 2006
• Last Update Posted: Mar 10, 2016
• Last Verified: Feb 1, 2016

• Additional relevant MeSH terms: Breast Neoplasms; Epirubicin; Epothilones

Study Results

Participant Flow

Arm/Group Title	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
Arm/Group Description	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.
Period Title: Enrollment
STARTED	0	0	0	42
COMPLETED	0	0	0	42
NOT COMPLETED	0	0	0	0
Period Title: Enrollment
STARTED	6	0	0	0
COMPLETED	0	0	0	0
NOT COMPLETED	6	0	0	0
Period Title: Enrollment
STARTED	0	30	0	0
COMPLETED	0	0	0	0
NOT COMPLETED	0	30	0	0
Period Title: Enrollment
STARTED	0	0	6	0
COMPLETED	0	0	0	0
NOT COMPLETED	0	0	6	0

Baseline Characteristics

Arm/Group Title	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
Arm/Group Description	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.	Total of all reporting groups
Overall Participants	6	30	6	42
Age, Customized (participants) [Number]
Between 18 and 65 years	6 100%	24 80%	5 83.3%	35 83.3%
>=65 years	0 0%	6 20%	1 16.7%	7 16.7%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57.5	57.5	53.5	57
Sex: Female, Male (Count of Participants)
Female	6 100%	30 100%	6 100%	42 100%
Male	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
France	5 83.3%	16 53.3%	3 50%	24 57.1%
Italy	1 16.7%	14 46.7%	3 50%	18 42.9%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Dose Limiting Toxicity (DLT)
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2
Arm/Group Description	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.
Measure Participants	6	6	6
Participants with DLT:Grade 4 (severe) neutropenia	1 16.7%	1 3.3%	2 33.3%
Total Participants with DLT	1 16.7%	1 3.3%	2 33.3%
Participants without DLT	5 83.3%	5 16.7%	4 66.7%

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	All Participants With Measurable Disease and Tumor Response
Arm/Group Description	All participants received Ixabepilone administered as a 3-hour IV infusion following a 3- to 5-minute IV infusion of Epirubicin every 21 days.
Measure Participants	42
MTD	30
R2PD	30

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2
Arm/Group Description	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.
Measure Participants	6	30	6
Deaths (total)	0 0%	0 0%	0 0%
Deaths within 30 days of last dose	0 0%	0 0%	0 0%
AEs	6 100%	30 100%	6 100%
SAEs	2 33.3%	8 26.7%	1 16.7%
Grade 3/4 AEs	6 100%	28 93.3%	6 100%
AEs leading to discontinuation of study treatment	4 66.7%	12 40%	1 16.7%

4. Secondary Outcome

Title	Maximum Plasma Concentration (Cmax) of Single-dose Ixabepilone
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2
Arm/Group Description	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.
Measure Participants	6	28	6
Mean (Standard Deviation) [ng/ml]	169.00 (44.42)	217.86 (53.56)	251.83 (48.56)

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2
Arm/Group Description	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.
Measure Participants	6	28	6
Mean (Standard Deviation) [ng·h/mL]	1760.42 (535.89)	2072.43 (399.60)	2100.56 (353.87)

6. Secondary Outcome

Title	Terminal Half-life (T-Half) of Single-dose Ixabepilone
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2
Arm/Group Description	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.
Measure Participants	6	28	6
Mean (Standard Deviation) [hours]	51.82 (15.47)	34.07 (11.75)	44.15 (18.41)

7. Secondary Outcome

Title	Clearance (CLT) of Single-dose Ixabepilone
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2
Arm/Group Description	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.
Measure Participants	6	28	6
Mean (Standard Deviation) [L/h]	26.03 (5.45)	24.62 (5.56)	26.68 (2.83)

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2
Arm/Group Description	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.
Measure Participants	6	28	6
Mean (Standard Deviation) [liters]	1331.65 (370.88)	803.21 (292.09)	1001.70 (317.23)

9. Secondary Outcome

Title	Epirubicin Cmax
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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2
Arm/Group Description	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.
Measure Participants	6	28	6
Mean (Standard Deviation) [ng/ml]	3306.53 (2125.45)	4139.00 (2598.19)	4533.08 (2490.83)

10. Secondary Outcome

Title	Epirubicin AUC(INF)
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2
Arm/Group Description	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.
Measure Participants	6	27	6
Mean (Standard Deviation) [ng·h/mL]	2489.37 (1488.39)	3132.67 (1685.32)	2595.44 (1017.64)

11. Secondary Outcome

Title	Epirubicin T-Half
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2
Arm/Group Description	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.
Measure Participants	6	27	6
Mean (Standard Deviation) [hours]	13.61 (3.33)	19.41 (6.31)	15.55 (2.92)

12. Secondary Outcome

Title	Epirubicin CLT
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2
Arm/Group Description	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.
Measure Participants	6	27	6
Mean (Standard Deviation) [L/h]	81.33 (70.84)	53.85 (32.87)	58.00 (38.82)

13. Secondary Outcome

Title	Epirubicin Vss
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2	Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2
Arm/Group Description	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.
Measure Participants	6	27	6
Mean (Standard Deviation) [liters]	912.83 (1500.018)	750.24 (977.352)	522.45 (657.97)

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	All Participants With Measurable Disease	All Response-evaluable Participants
Arm/Group Description	Participants with measurable disease at baseline per RECIST	Participants treated at the MTD with measurable disease at baseline per RECIST
Measure Participants	32	22
Complete Response	0 0%	0 0%
Partial Response	18 300%	9 30%
Stable Disease	11 183.3%	10 33.3%
Progressive Disease	3 50%	3 10%

15. Secondary Outcome

Title	Duration of Tumor Response
Description	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	All Participants With Measurable Disease and Tumor Response	All Response-evaluable Participants
Arm/Group Description	All participants with measurable disease and with a best tumor response of either CR or PR.	Participants treated at the MTD with a best response of either CR or PR.
Measure Participants	18	9
Median (Full Range) [months]	6.45	6.4

16. Secondary Outcome

Title	Number Of Participants With Tumor Response by Duration of Response Category
Description	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	All Participants With Measurable Disease and Tumor Response	All Response-evaluable Participants
Arm/Group Description	All participants with measurable disease and with a best tumor response of either CR or PR.	Participants treated at the MTD with a best response of either CR or PR.
Measure Participants	18	9
Response Duration < 4 Months	5 83.3%	1 3.3%
Response Duration ≥4 Months	13 216.7%	8 26.7%
Response Duration ≥6 Months	11 183.3%	6 20%

Adverse Events

Arm/Group Title	Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2		Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2		Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2
Arm/Group Description	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.
All Cause Mortality
	Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2		Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2		Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2		Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2		Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/6 (33.3%)		8/30 (26.7%)		1/6 (16.7%)
Blood and lymphatic system disorders
ANAEMIA	0/6 (0%)		1/30 (3.3%)		0/6 (0%)
NEUTROPENIA	0/6 (0%)		0/30 (0%)		1/6 (16.7%)
FEBRILE NEUTROPENIA	0/6 (0%)		1/30 (3.3%)		0/6 (0%)
FEBRILE BONE MARROW APLASIA	0/6 (0%)		2/30 (6.7%)		0/6 (0%)
Gastrointestinal disorders
NAUSEA	0/6 (0%)		2/30 (6.7%)		0/6 (0%)
VOMITING	1/6 (16.7%)		0/30 (0%)		0/6 (0%)
General disorders
PYREXIA	0/6 (0%)		2/30 (6.7%)		0/6 (0%)
Immune system disorders
HYPERSENSITIVITY	1/6 (16.7%)		0/30 (0%)		0/6 (0%)
Investigations
PLATELET COUNT DECREASED	0/6 (0%)		0/30 (0%)		1/6 (16.7%)
Musculoskeletal and connective tissue disorders
BACK PAIN	0/6 (0%)		1/30 (3.3%)		0/6 (0%)
Nervous system disorders
SYNCOPE	0/6 (0%)		0/30 (0%)		1/6 (16.7%)
CEREBROVASCULAR ACCIDENT	0/6 (0%)		1/30 (3.3%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2		Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2		Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		30/30 (100%)		6/6 (100%)
Blood and lymphatic system disorders
ANAEMIA	5/6 (83.3%)		20/30 (66.7%)		3/6 (50%)
LEUKOPENIA	3/6 (50%)		11/30 (36.7%)		3/6 (50%)
NEUTROPENIA	6/6 (100%)		30/30 (100%)		6/6 (100%)
THROMBOCYTOPENIA	1/6 (16.7%)		2/30 (6.7%)		0/6 (0%)
Cardiac disorders
TACHYCARDIA	1/6 (16.7%)		1/30 (3.3%)		0/6 (0%)
LEFT VENTRICULAR DYSFUNCTION	1/6 (16.7%)		0/30 (0%)		0/6 (0%)
Eye disorders
CONJUNCTIVITIS	0/6 (0%)		2/30 (6.7%)		1/6 (16.7%)
LACRIMATION INCREASED	1/6 (16.7%)		0/30 (0%)		0/6 (0%)
Gastrointestinal disorders
NAUSEA	5/6 (83.3%)		25/30 (83.3%)		4/6 (66.7%)
VOMITING	3/6 (50%)		21/30 (70%)		4/6 (66.7%)
DIARRHOEA	0/6 (0%)		7/30 (23.3%)		3/6 (50%)
DYSPEPSIA	1/6 (16.7%)		0/30 (0%)		1/6 (16.7%)
GASTRITIS	0/6 (0%)		5/30 (16.7%)		2/6 (33.3%)
STOMATITIS	0/6 (0%)		5/30 (16.7%)		0/6 (0%)
CONSTIPATION	1/6 (16.7%)		10/30 (33.3%)		1/6 (16.7%)
HAEMORRHOIDS	0/6 (0%)		2/30 (6.7%)		1/6 (16.7%)
GINGIVAL PAIN	1/6 (16.7%)		0/30 (0%)		0/6 (0%)
ABDOMINAL PAIN UPPER	0/6 (0%)		3/30 (10%)		0/6 (0%)
General disorders
FATIGUE	0/6 (0%)		4/30 (13.3%)		1/6 (16.7%)
PYREXIA	1/6 (16.7%)		3/30 (10%)		1/6 (16.7%)
ASTHENIA	4/6 (66.7%)		16/30 (53.3%)		2/6 (33.3%)
HYPERTHERMIA	1/6 (16.7%)		0/30 (0%)		0/6 (0%)
MUCOSAL INFLAMMATION	0/6 (0%)		10/30 (33.3%)		1/6 (16.7%)
Immune system disorders
HYPERSENSITIVITY	0/6 (0%)		3/30 (10%)		0/6 (0%)
Infections and infestations
ONYCHOMYCOSIS	1/6 (16.7%)		0/30 (0%)		0/6 (0%)
NASOPHARYNGITIS	0/6 (0%)		0/30 (0%)		1/6 (16.7%)
URINARY TRACT INFECTION	0/6 (0%)		0/30 (0%)		1/6 (16.7%)
VULVOVAGINAL MYCOTIC INFECTION	1/6 (16.7%)		0/30 (0%)		0/6 (0%)
Investigations
WEIGHT DECREASED	2/6 (33.3%)		6/30 (20%)		1/6 (16.7%)
HAEMOGLOBIN DECREASED	1/6 (16.7%)		8/30 (26.7%)		3/6 (50%)
PLATELET COUNT DECREASED	1/6 (16.7%)		1/30 (3.3%)		1/6 (16.7%)
BLOOD CREATININE INCREASED	0/6 (0%)		2/30 (6.7%)		0/6 (0%)
ALANINE AMINOTRANSFERASE INCREASED	1/6 (16.7%)		2/30 (6.7%)		1/6 (16.7%)
ASPARTATE AMINOTRANSFERASE INCREASED	0/6 (0%)		3/30 (10%)		2/6 (33.3%)
BLOOD ALKALINE PHOSPHATASE INCREASED	0/6 (0%)		0/30 (0%)		1/6 (16.7%)
ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED	0/6 (0%)		0/30 (0%)		1/6 (16.7%)
Metabolism and nutrition disorders
ANOREXIA	1/6 (16.7%)		5/30 (16.7%)		2/6 (33.3%)
HYPERGLYCAEMIA	0/6 (0%)		3/30 (10%)		1/6 (16.7%)
Musculoskeletal and connective tissue disorders
MYALGIA	0/6 (0%)		11/30 (36.7%)		4/6 (66.7%)
ARTHRITIS	1/6 (16.7%)		0/30 (0%)		0/6 (0%)
BACK PAIN	0/6 (0%)		2/30 (6.7%)		0/6 (0%)
BONE PAIN	0/6 (0%)		3/30 (10%)		0/6 (0%)
ARTHRALGIA	2/6 (33.3%)		9/30 (30%)		3/6 (50%)
MUSCLE SPASMS	1/6 (16.7%)		3/30 (10%)		0/6 (0%)
PAIN IN EXTREMITY	1/6 (16.7%)		4/30 (13.3%)		1/6 (16.7%)
Nervous system disorders
HEADACHE	2/6 (33.3%)		6/30 (20%)		1/6 (16.7%)
AREFLEXIA	1/6 (16.7%)		3/30 (10%)		0/6 (0%)
DYSGEUSIA	0/6 (0%)		9/30 (30%)		2/6 (33.3%)
DYSAESTHESIA	0/6 (0%)		5/30 (16.7%)		1/6 (16.7%)
HYPOREFLEXIA	3/6 (50%)		10/30 (33.3%)		2/6 (33.3%)
PARAESTHESIA	5/6 (83.3%)		15/30 (50%)		3/6 (50%)
SENSORY LOSS	2/6 (33.3%)		9/30 (30%)		0/6 (0%)
HYPOAESTHESIA	1/6 (16.7%)		2/30 (6.7%)		2/6 (33.3%)
HYPERAESTHESIA	0/6 (0%)		3/30 (10%)		0/6 (0%)
CRANIAL NEUROPATHY	0/6 (0%)		0/30 (0%)		1/6 (16.7%)
PERIPHERAL SENSORY NEUROPATHY	1/6 (16.7%)		2/30 (6.7%)		1/6 (16.7%)
Psychiatric disorders
ANXIETY	1/6 (16.7%)		1/30 (3.3%)		0/6 (0%)
Renal and urinary disorders
DYSURIA	1/6 (16.7%)		0/30 (0%)		0/6 (0%)
Reproductive system and breast disorders
BARTHOLINITIS	0/6 (0%)		0/30 (0%)		1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
COUGH	1/6 (16.7%)		2/30 (6.7%)		0/6 (0%)
DYSPHONIA	0/6 (0%)		3/30 (10%)		0/6 (0%)
RHINORRHOEA	1/6 (16.7%)		3/30 (10%)		0/6 (0%)
LUNG INFILTRATION	1/6 (16.7%)		0/30 (0%)		0/6 (0%)
Skin and subcutaneous tissue disorders
RASH	0/6 (0%)		0/30 (0%)		1/6 (16.7%)
BLISTER	1/6 (16.7%)		0/30 (0%)		0/6 (0%)
ALOPECIA	6/6 (100%)		21/30 (70%)		6/6 (100%)
DRY SKIN	2/6 (33.3%)		0/30 (0%)		0/6 (0%)
HYPERHIDROSIS	0/6 (0%)		0/30 (0%)		1/6 (16.7%)
NAIL DISORDER	3/6 (50%)		4/30 (13.3%)		0/6 (0%)
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME	2/6 (33.3%)		1/30 (3.3%)		0/6 (0%)
Vascular disorders
HOT FLUSH	0/6 (0%)		2/30 (6.7%)		1/6 (16.7%)
VENOUS INSUFFICIENCY	1/6 (16.7%)		1/30 (3.3%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.