Ixabepilone and Liposomal Doxorubicin in Advanced Ovarian Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00182767
• Collaborator: (none)
• Enrollment: 45
• Locations: 5
• Arm: 1
• Duration (Months): 99.9
• Patients Per Site: 9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This trial is studying the side effects and best dose of ixabepilone when given together with pegylated liposomal doxorubicin hydrochloride and to see how well they work in treating women with advanced ovarian epithelial, primary peritoneal cavity, or fallopian tube cancer or metastatic breast cancer. Drugs used in chemotherapy, such as ixabepilone and pegylated liposomal doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

Condition or Disease	Intervention/Treatment	Phase
Fallopian Tube Cancer; Female Reproductive Cancer; Recurrent Breast Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer	Drug: ixabepilone; Drug: pegylated liposomal doxorubicin hydrochloride	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the maximum tolerated dose and recommended phase II dose of ixabepilone when combined with pegylated doxorubicin hydrochloride (HCl) liposome (pegylated liposomal doxorubicin hydrochloride) in women with previously treated advanced ovarian epithelial, primary peritoneal cavity, or fallopian tube cancer or metastatic breast cancer.

2. To determine the safety profile of this regimen in these patients. III. To determine the clinical efficacy of this regimen in patients with platinum- and taxane-resistant advanced ovarian epithelial, primary peritoneal cavity, or fallopian tube cancer.

OUTLINE: This is a phase I, multicenter, open-label, dose-escalation study of ixabepilone followed by a phase II study.

Patients receive ixabepilone intravenously (IV) over 3 hours and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1. Courses repeat every 21-28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for up to 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Study of BMS-247550 and Pegylated Liposomal Doxorubicin (Doxil®) in Patients With Advanced Epithelial Ovarian Cancer or Primary Peritoneal Cancer Who Have Been Previously Treated With a Platinum and a Taxane
• Study Start Date: Jan 1, 2006
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (ixabepilone and doxorubicin) Ixabepilone IV over 3 hours and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1.	Drug: ixabepilone; Given IV; Other Names: BMS-247550 epothilone B lactam Ixempra ; Drug: pegylated liposomal doxorubicin hydrochloride; Given IV; Other Names: CAELYX Dox-SL DOXIL doxorubicin hydrochloride liposome LipoDox

Outcome Measures

Primary Outcome Measures

1. Incidence of Dose-limiting Toxicity (DLT), Graded Using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 4.0 (Phase I) [28 days]

   Dose-Limiting Toxicities are assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events classification and usually encompasses all grade 3 or higher toxicities

2. Maximum Tolerated Dose [Once 2 DLT events occur in patients during the first 28 days of treatment (cycle 1), the preceding dose will be designated the maximum tolerated dose (MTD).]

   The phase I component of the study included 30 patients with breast and ovarian cancer. A protocol amendment was made during phase I trial from a treatment regimen of Schedule A (ixabepilone every 3-4 weeks) to Schedule B (ixabepilone every week). The maximum tolerated dose was determined to be the preceding dose of any dose that resulted in 2 DLT events. Schedule B was carried forward to the phase II trial. The Maximum Tolerated Dose for Schedule B is reported. Please see (Chuang et al., 2010) for additional details

Secondary Outcome Measures

1. Proportion of Patients Responding to Therapy (Complete Response [CR], Partial Response [PR], or Stable Disease [SD]), Assessed According to Response Evaluation Criteria in Solid Tumors (RECIST) and Cancer Antigen-125 (CA-125) Response Criteria (Phase II) [Up to 2 years]

2. Progression-free Survival [The time from start of treatment to time of progression or death, assessed up to 2 years]

   We will summarize progression-free survival by Kaplan-Meier survival analysis.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of 1 of the following: advanced ovarian epithelial, primary peritoneal cavity, or fallopian tube cancer (phase I and

1. or metastatic breast cancer (phase I only).

• Platinum- and taxane-resistant disease, defined as a disease-free interval of < 6 months after completion of platinum- and taxane-based chemotherapy. Disease progression during the regimen (phase II) or previously treated with >= 2 prior regimens for metastatic breast cancer, including 1 taxane-based regimen in the adjuvant or metastatic setting (phase I).

• Meets 1 of the following criteria: Previously treated with a standard course of taxane- and platinum-based chemotherapy for ovarian epithelial, primary peritoneal cavity, or fallopian tube cancer, that is platinum-refractory or -sensitive disease (phase I );

• Measurable or evaluable disease, meeting 1 of the following criteria: unidimensionally measurable lesion, known disease and CA 125 > 50 U/mL on 2 occasions >= 1 week apart or known disease and CA 27-29, CA 15-3, or CA 125 > 50 U/mL on 2 occasions >= 1 week apart (for breast cancer patients)

• ECOG 0-2 or Karnofsky 60-100%

• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered.

• At least 1 week since prior chemotherapy if given on a daily or weekly schedule and recovered.

• At least 3 weeks since prior radiotherapy and recovered.

• Recovered for more than 4 weeks from all adverse events related to prior agents.

• Normal organ function including:

• Normal bilirubin

• WBC >= 3,000/mm3

• Absolute neutrophil count >= 1,500/mm3

• Platelet count >= 100,000/mm3

• AST and ALT =< 2.5 times upper limit of normal (ULN)

• Creatinine =< 1.5 times ULN or Creatinine clearance ≥ 60 mL/min

Exclusion criteria:

• No other concurrent investigational agents.

• No concurrent combination antiretroviral therapy for HIV-positive patients.

• No other concurrent anticancer therapy.

• Has received a previous chemotherapy regimen for this cancer that included drugs such as docetaxel or paclitaxel.

• Life expectancy of more than 3 months

• No symptomatic congestive heart failure

• No unstable angina pectoris

• No cardiac arrhythmia

• Not pregnant or nursing

• Fertile patients must use effective contraception

• No history of allergic reaction attributed to compounds of similar chemical or biological composition to Cremophor® or study drugs

• No neuropathy >= grade 2

• No ongoing or active infection

• No psychiatric illness or social situation that would preclude study compliance.

• No other uncontrolled illness.

• No active brain metastases, including any of the following: evidence of cerebral edema by CT scan or MRI, evidence of disease progression on prior imaging studies, requirement for steroids or clinical symptoms of brain metastasis.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Connecticut	Farmington	Connecticut	United States	06030
2	Women's Cancer Care Associates LLC	Albany	New York	United States	12208
3	Albert Einstein College of Medicine	Bronx	New York	United States	10461
4	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467-2490
5	Weill Medical College of Cornell University	New York	New York	United States	10065

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ellen Chuang, Montefiore Medical Center - Moses Campus

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00182767
• Other Study ID Numbers: NCI-2009-00140; NCI-2009-00140; 0504007857; 7229; N01CM62204; P30CA013330
• First Posted: Sep 16, 2005
• Last Update Posted: Mar 10, 2016
• Last Verified: Feb 1, 2014

• Additional relevant MeSH terms: Breast Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Recurrence; Doxorubicin; Liposomal doxorubicin; Epothilone B; Epothilones

Study Results

Participant Flow

Recruitment Details	A total of 45 patients were enrolled and treated between January 2006 and May 2011

Arm/Group Title	Ixabepilone: 24mg/m2 and Doxil 30 mg/m2: Level 1	Ixabepilone: 32mg/m2 and Doxil 30 mg/m2: Level 2	Ixabepilone: 40mg/m2 and Doxil 30 mg/m2: Level 3	Ixabepilone: 13mg/m2 and Doxil 30 mg/m2: Level 4	Ixabepilone: 16mg/m2 and Doxil 30 mg/m2: Level 5
Arm/Group Description	Ixabepilone IV over 3 hours and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1. ixabepilone: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV	Ixabepilone IV over 3 hours and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1. ixabepilone: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV	Ixabepilone IV over 3 hours and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1. ixabepilone: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV	Ixabepilone IV over 3 hours on days 1, 8 and 15 and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1. ixabepilone: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV	Ixabepilone IV over 3 hours on days 1, 8 and 15 and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1. ixabepilone: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV
Period Title: Overall Study
STARTED	6	6	6	3	24
COMPLETED	6	6	6	3	24
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Treatment (Ixabepilone and Doxorubicin)
Arm/Group Description	Ixabepilone IV over 3 hours and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes. ixabepilone: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV
Overall Participants	45
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59
Sex: Female, Male (Count of Participants)
Female	45 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Incidence of Dose-limiting Toxicity (DLT), Graded Using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 4.0 (Phase I)
Description	Dose-Limiting Toxicities are assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events classification and usually encompasses all grade 3 or higher toxicities
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ixabepilone 24mg/m2 and Doxorubicin 30mg/m2: Level 1	Ixabepilone 32mg/m2 and Doxorubicin 30mg/m2: Level 2	Ixabepilone 40mg/m2 and Doxorubicin 30mg/m2: Level 3	Ixabepilone 13mg/m2 and Doxorubicin 30mg/m2: Level 4	Ixabepilone 16mg/m2 and Doxorubicin 30mg/m2: Level 5
Arm/Group Description	Ixabepilone IV over 3 hours and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1 every 21 days ixabepilone: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV	Ixabepilone IV over 3 hours and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1 every 21 days ixabepilone: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV	Ixabepilone IV over 3 hours and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1 every 21 days ixabepilone: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV	Ixabepilone IV over 3 hours on days 1, 8 and 15 and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1 every 28 days ixabepilone: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV	Ixabepilone IV over 3 hours on days 1, 8 and 15 and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1 every 28 days ixabepilone: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV
Measure Participants	6	6	6	3	9
Number [participants]	1 2.2%	1 NaN	2 NaN	0 NaN	0 NaN

2. Secondary Outcome

Title	Proportion of Patients Responding to Therapy (Complete Response [CR], Partial Response [PR], or Stable Disease [SD]), Assessed According to Response Evaluation Criteria in Solid Tumors (RECIST) and Cancer Antigen-125 (CA-125) Response Criteria (Phase II)
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Ixabepilone and Doxorubicin)
Arm/Group Description	Ixabepilone IV over 3 hours and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes. ixabepilone: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV
Measure Participants	45
Ovarian Cancer	20 44.4%
Breast Cancer	7 15.6%

3. Secondary Outcome

Title	Progression-free Survival
Description	We will summarize progression-free survival by Kaplan-Meier survival analysis.
Time Frame	The time from start of treatment to time of progression or death, assessed up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Ixabepilone and Doxorubicin)
Arm/Group Description	Ixabepilone IV over 3 hours and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1. ixabepilone: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV
Measure Participants	45
Median (95% Confidence Interval) [months]	4.1

4. Primary Outcome

Title	Maximum Tolerated Dose
Description	The phase I component of the study included 30 patients with breast and ovarian cancer. A protocol amendment was made during phase I trial from a treatment regimen of Schedule A (ixabepilone every 3-4 weeks) to Schedule B (ixabepilone every week). The maximum tolerated dose was determined to be the preceding dose of any dose that resulted in 2 DLT events. Schedule B was carried forward to the phase II trial. The Maximum Tolerated Dose for Schedule B is reported. Please see (Chuang et al., 2010) for additional details
Time Frame	Once 2 DLT events occur in patients during the first 28 days of treatment (cycle 1), the preceding dose will be designated the maximum tolerated dose (MTD).

Outcome Measure Data

Analysis Population Description

The phase I component of the study included 30 patients with breast and ovarian cancer.

Arm/Group Title	Treatment (Ixabepilone and Doxorubicin)
Arm/Group Description	Ixabepilone IV over 3 hours and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes. ixabepilone: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV
Measure Participants	30
Number [mg/m2]	16

Adverse Events

Arm/Group Title	Ixabepilone 24mg/m2 and Doxorubicin 30mg/m2: Level 1		Ixabepilone 32mg/m2 and Doxorubicin 30mg/m2: Level 2		Ixabepilone 40mg/m2 and Doxorubicin 30mg/m2: Level 3		Ixabepilone 13mg/m2 and Doxorubicin 30mg/m2: Level 4		Ixabepilone 16mg/m2 and Doxorubicin 30mg/m2: Level 5
Arm/Group Description	Ixabepilone IV over 3 hours and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1. ixabepilone: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV		Ixabepilone IV over 3 hours and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1. ixabepilone: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV		Ixabepilone IV over 3 hours and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1. ixabepilone: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV		Ixabepilone IV over 3 hours on days 1, 8 and 15 and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1 ixabepilone: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV		Ixabepilone IV over 3 hours on days 1, 8 and 15 and pegylated liposomal doxorubicin hydrochloride IV over 30-60 minutes on day 1 ixabepilone: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV
All Cause Mortality
	Ixabepilone 24mg/m2 and Doxorubicin 30mg/m2: Level 1		Ixabepilone 32mg/m2 and Doxorubicin 30mg/m2: Level 2		Ixabepilone 40mg/m2 and Doxorubicin 30mg/m2: Level 3		Ixabepilone 13mg/m2 and Doxorubicin 30mg/m2: Level 4		Ixabepilone 16mg/m2 and Doxorubicin 30mg/m2: Level 5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Ixabepilone 24mg/m2 and Doxorubicin 30mg/m2: Level 1		Ixabepilone 32mg/m2 and Doxorubicin 30mg/m2: Level 2		Ixabepilone 40mg/m2 and Doxorubicin 30mg/m2: Level 3		Ixabepilone 13mg/m2 and Doxorubicin 30mg/m2: Level 4		Ixabepilone 16mg/m2 and Doxorubicin 30mg/m2: Level 5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		6/6 (100%)		6/6 (100%)		3/3 (100%)		24/24 (100%)
Blood and lymphatic system disorders
Anemia	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	4/24 (16.7%)	4
Gastrointestinal disorders
Constipation	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Mucositis	1/6 (16.7%)	1	2/6 (33.3%)	2	1/6 (16.7%)	1	0/3 (0%)	0	2/24 (8.3%)	2
Vomiting	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Dehydration	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Abdominal pain	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/24 (4.2%)	1
Small intestinal obstruction	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/24 (8.3%)	2
Nausea	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/24 (4.2%)	1
Ascites	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/24 (4.2%)	1
Diarrhea	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/24 (4.2%)	1
General disorders
Fatigue	0/6 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	2	0/3 (0%)	0	2/24 (8.3%)	2
Death NOS	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/24 (4.2%)	1
Infections and infestations
Infection with grade 3 or 4 neutrophils	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Lung infections	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Catheter related infection	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/24 (0%)	0
Investigations
Blood Bilirubin increased	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
White blood cell count decreased	1/6 (16.7%)	1	1/6 (16.7%)	1	1/6 (16.7%)	1	2/3 (66.7%)	2	1/24 (4.2%)	1
Neutrophils count decreased	1/6 (16.7%)	1	1/6 (16.7%)	1	1/6 (16.7%)	1	1/3 (33.3%)	1	5/24 (20.8%)	5
Platelet count decreased	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/24 (8.3%)	2
Metabolism and nutrition disorders
Hypokalemia	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Hypophosphatemia	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/24 (4.2%)	1
Hypercalcemia	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/24 (4.2%)	1
Musculoskeletal and connective tissue disorders
Bone pain	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Chest Wall Pain	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Nervous system disorders
CNS cerebrovascular ischemia	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Neuropathy: Sensory	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Headache	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Ataxia	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/24 (4.2%)	1
Psychiatric disorders
Anxiety	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/24 (4.2%)	1
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Dyspnea	0/6 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1	0/3 (0%)	0	1/24 (4.2%)	1
Pleural Effusion	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/24 (4.2%)	1
Skin and subcutaneous tissue disorders
Rash: desquamation	0/6 (0%)	0	0/6 (0%)	0	3/6 (50%)	3	0/3 (0%)	0	1/24 (4.2%)	1
Hand-foot skin reaction	1/6 (16.7%)	1	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Vascular disorders
Thromboembolic event	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	1/3 (33.3%)	1	2/24 (8.3%)	2
Hot flashes	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/24 (4.2%)	1
Other (Not Including Serious) Adverse Events
	Ixabepilone 24mg/m2 and Doxorubicin 30mg/m2: Level 1		Ixabepilone 32mg/m2 and Doxorubicin 30mg/m2: Level 2		Ixabepilone 40mg/m2 and Doxorubicin 30mg/m2: Level 3		Ixabepilone 13mg/m2 and Doxorubicin 30mg/m2: Level 4		Ixabepilone 16mg/m2 and Doxorubicin 30mg/m2: Level 5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		6/6 (100%)		6/6 (100%)		3/3 (100%)		24/24 (100%)
Blood and lymphatic system disorders
Anemia	0/6 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	2	2/3 (66.7%)	2	9/24 (37.5%)	9
Cardiac disorders
Sinus tachycardia	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Palpitations	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/24 (8.3%)	2
Eye disorders
Blurred vision	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/24 (8.3%)	2
Dry eye	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Gastrointestinal disorders
Nausea	3/6 (50%)	3	2/6 (33.3%)	2	2/6 (33.3%)	2	2/3 (66.7%)	2	11/24 (45.8%)	11
Anorexia	2/6 (33.3%)	2	2/6 (33.3%)	2	2/6 (33.3%)	2	2/3 (66.7%)	2	7/24 (29.2%)	7
Dyspepsia	2/6 (33.3%)	2	0/6 (0%)	0	2/6 (33.3%)	2	2/3 (66.7%)	2	1/24 (4.2%)	1
Vomiting	1/6 (16.7%)	1	0/6 (0%)	0	1/6 (16.7%)	1	2/3 (66.7%)	2	6/24 (25%)	6
Abdominal distension	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/24 (8.3%)	2
Ascites	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Diarrhea	0/6 (0%)	0	2/6 (33.3%)	2	1/6 (16.7%)	1	2/3 (66.7%)	2	6/24 (25%)	6
Small intestinal obstruction	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Constipation	0/6 (0%)	0	2/6 (33.3%)	2	2/6 (33.3%)	2	1/3 (33.3%)	1	7/24 (29.2%)	7
Dysphagia	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	2/24 (8.3%)	2
Mucositis oral	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	2/3 (66.7%)	2	7/24 (29.2%)	7
Esophagitis	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	1/24 (4.2%)	1
Abdominal pain	0/6 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	2	0/3 (0%)	0	3/24 (12.5%)	3
Dehydration	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/24 (0%)	0
Dry mouth	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/24 (8.3%)	2
General disorders
Fatigue	3/6 (50%)	3	3/6 (50%)	3	0/6 (0%)	0	3/3 (100%)	3	15/24 (62.5%)	15
Fever	0/6 (0%)	0	3/6 (50%)	3	1/6 (16.7%)	1	0/3 (0%)	0	1/24 (4.2%)	1
Chills	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	1/24 (4.2%)	1
Edema limbs	0/6 (0%)	0	2/6 (33.3%)	2	1/6 (16.7%)	1	0/3 (0%)	0	6/24 (25%)	6
Gait disturbance	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/24 (8.3%)	2
Hepatobiliary disorders
Hepatic Pain	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/24 (0%)	0
Infections and infestations
Rash maculo-papular	1/6 (16.7%)	1	1/6 (16.7%)	1	0/6 (0%)	0	2/3 (66.7%)	2	6/24 (25%)	6
Soft tissue infection	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Upper respiratory infection	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	1/24 (4.2%)	1
skin infection	0/6 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	2	0/3 (0%)	0	0/24 (0%)	0
Nail infection	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/24 (0%)	0
Urinary tract infection	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	3/24 (12.5%)	3
Injury, poisoning and procedural complications
Bruising	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/24 (8.3%)	2
Investigations
Platelet count decreased	1/6 (16.7%)	1	0/6 (0%)	0	1/6 (16.7%)	1	2/3 (66.7%)	2	1/24 (4.2%)	1
Creatinine increased	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Metabolism and nutrition disorders
Hypoglycemia	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/24 (8.3%)	2
Hypokalemia	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/24 (8.3%)	2
Musculoskeletal and connective tissue disorders
Pain in extremity	2/6 (33.3%)	2	0/6 (0%)	0	2/6 (33.3%)	2	0/3 (0%)	0	4/24 (16.7%)	4
Back pain	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	3/24 (12.5%)	3
Neck pain	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Myalgia	1/6 (16.7%)	1	2/6 (33.3%)	2	1/6 (16.7%)	1	0/3 (0%)	0	1/24 (4.2%)	1
Arthralgia	0/6 (0%)	0	2/6 (33.3%)	2	1/6 (16.7%)	1	0/3 (0%)	0	1/24 (4.2%)	1
Generalized muscle weakness	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/24 (0%)	0
Bone pain	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/24 (0%)	0
Nervous system disorders
Dysgeusia	1/6 (16.7%)	1	1/6 (16.7%)	1	2/6 (33.3%)	2	1/3 (33.3%)	1	3/24 (12.5%)	3
Peripheral motor neuropathy	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Headache	1/6 (16.7%)	1	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	4/24 (16.7%)	4
Peripheral sensory neuropathy	0/6 (0%)	0	1/6 (16.7%)	1	3/6 (50%)	3	1/3 (33.3%)	1	10/24 (41.7%)	10
Ischemia cerebrovascular	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/24 (0%)	0
Dizziness	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	4/24 (16.7%)	4
Psychiatric disorders
Insomnia	1/6 (16.7%)	1	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	4/24 (16.7%)	4
Depression	0/6 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1	0/3 (0%)	0	2/24 (8.3%)	2
Depression	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/24 (8.3%)	2
Anxiety	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/24 (8.3%)	2
Renal and urinary disorders
Urinary tract pain	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/24 (0%)	0
Reproductive system and breast disorders
Breast pain	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Vaginal dryness	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Vaginal inflammation	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Vaginal hemorrhage	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/24 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hiccups	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/24 (4.2%)	1
Pharyngolaryngeal pain	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/24 (0%)	0
Sinus disorder	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	1/3 (33.3%)	1	1/24 (4.2%)	1
Pleural effusion	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Dyspnea	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	1/3 (33.3%)	1	5/24 (20.8%)	5
Voice alteration	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/24 (0%)	0
Cough	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	2/3 (66.7%)	2	5/24 (20.8%)	5
Allergic Rhinitis	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	6/24 (25%)	6
Skin and subcutaneous tissue disorders
Alopecia	2/6 (33.3%)	2	2/6 (33.3%)	2	2/6 (33.3%)	2	1/3 (33.3%)	1	6/24 (25%)	6
Nail loss	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/24 (0%)	0
Hand and foot syndrome	0/6 (0%)	0	0/6 (0%)	0	4/6 (66.7%)	4	0/3 (0%)	0	2/24 (8.3%)	2
Skin hyperpigmentation	0/6 (0%)	0	0/6 (0%)	0	3/6 (50%)	3	0/3 (0%)	0	2/24 (8.3%)	2
Pruritus	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/24 (0%)	0
Rash: acneiform	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	3/24 (12.5%)	3
Dry skin	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/24 (8.3%)	2
Vascular disorders
Phlebitis	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/24 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.