Metastatic Breast Cancer
Conditions
Brief summary
The purpose of this clinical research study is to learn if ixabepilone plus bevacizumab is effective in shrinking or stopping the growth of cancer when given as first-line chemotherapy in participants with metastatic breast cancer. The study will also assess the safety of this combination treatment.
Interventions
DRUGIxabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg
Ixabepilone,16 mg/m\^2, administered as a 1-hour intravenous (IV) infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered as IV infusion every 2 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.
DRUGIxabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg
Ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity (After Cycle 4, dose reduction to 32 mg/m\^2 was to be implemented for all subsequent cycles.) Bevacizumab, 15 mg/kg, administered as IV infusion every 3 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.
DRUGPaclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg
Paclitaxel, 90 mg/m\^2, given as a 1-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered as IV infusion every 2 weeks. Bevacizumab infused over 90 minutes for the first dose, and if well tolerated, over 60 minutes for the second dose. If still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.
Sponsors
R-Pharm
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Locally recurrent or metastatic breast cancer, previously untreated with chemotherapy for advanced disease. * At least 1 target lesion per RECIST criteria. Locally recurrent disease must not be amenable to resection with curative intent. * No previous cytotoxic chemotherapy for locally recurrent/metastatic disease. * Relapse 12 months or more after completing prior adjuvant or neoadjuvant taxane therapy. * No previous breast cancer known to overexpress or amplify the human epidermal growth factor receptor 2 gene. * Prior hormonal therapy in adjuvant, recurrent, or metastatic setting allowed but must have been discontinued at least 2 weeks before randomization. * Karnofsky performance status of 80 to 100 or Eastern Cooperative Oncology Group performance status of 0 to 1. * Estimated life expectancy of at least 12 weeks. * Recovery from recent therapy (except for alopecia), including chemotherapy, immunotherapy, biologic therapy, or investigational product. Any such therapy must have been completed at least 3 weeks before randomization and at least 6 weeks from use of nitrosourea, or mitomycin. * Recovery from recent surgery and radiation therapy. At least 1 week since minor surgery and/or focal/palliative radiation therapy; at least 3 weeks from radiation; at least 4 weeks from major surgery; and at least 8 weeks from liver resection, thoracotomy, or neurosurgery. * Absolute neutrophil count ≥1500/mm\^3. * Hemoglobin ≥9 g/dL. * Platelets ≥100,000/mm\^3. * Total bilirubin ≤1.5 times the upper limit of normal (ULN). * Aspartate aminotransferase or alanine aminotransferase ≤2.5\*ULN. * Normal partial thromboplastin time and either international normalized ratio or prothrombin time \<1.5\*ULN. * Serum creatinine ≤1.5\*ULN or 24-hour creatinine clearance \>60 mL/min. * Urine dipstick for proteinuria \<2+ (negative, trace, or +1). Participants with ≥2+ proteinuria at baseline were to undergo 24-hour urine collection and demonstrate ≤1g of protein in 24 hours to be eligible.
Exclusion criteria
* Women of child-bearing potential (WOCBP) unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and up to 6 months after treatment with bevacizumab. * Women who were pregnant or breastfeeding. * Women with a positive pregnancy test on enrollment or prior to study drug administration. * Sexually active fertile men, whose partners were WOCBP, not using an adequate method of birth control. * Evidence of baseline sensory or motor neuropathy. * Serious infection or nonmalignant medical illnesses uncontrolled or the control of which could be jeopardized by this therapy. * History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, serious gastric ulcer, or bone fracture within 6 months of study entry. * History of hypertensive crisis or hypertensive encephalopathy. * Significant vascular disease. * Clinically significant cardiovascular disease. * Baseline left ventricular ejection fraction by multiple-gated acquisition scan or echocardiogram for subjects with prior exposure to anthracyclines not within institutional normal limits. * Symptomatic peripheral vascular disease. * History of high dose chemotherapy with bone marrow transplant or peripheral blood stem cell transplant within the previous 2 years. * Evidence of bleeding diathesis or coagulopathy. * Prior treatment with an epothilone or any antiangiogenic agent. * Concurrent nonhealing wound, ulcer, or fracture. * Any current or history of brain and/or leptomeningeal metastases. Psychiatric disorders or other conditions rendering the participant incapable of complying with the requirements of the protocol. * Any concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix. * Known allergy to any of the study drugs or their excipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Best Tumor Response of Partial Response (PR) or Complete Response (CR) While On-study | Baseline visit and then every 8 weeks to 12 months, then every 3 months until disease progression | CR=Disappearance of all clinical and radiologic evidence of target lesions; PR=At least 30% reduction in the sum of the longest diameter of all target lesions. |
| Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) | Baseline visit and then every 8 weeks to 12 months, then every 3 months until disease progression | Best tumor response was assessed with RECIST. Complete response (CR)=Disappearance of all evidence of target lesions; Partial response (PR)=At least 30% reduction from baseline in the sum of the longest diameter (LD) of all target lesions; Progressive disease (PD)=At least a 20% increase from baseline in the sum of LD of target lesions or the appearance of 1 or more new lesions; Stable disease (SD)=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. A response was confirmed if noted on 2 examinations at least 4 weeks apart. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Time to Response | Date of first PR or CR assessment to date of progression, death, or last tumor assessment (maximum participant time to response of 67 weeks) | Time to response was defined as the time from the first dose of study therapy until measurement criteria were first met for a PR or CR, whichever was recorded first. Time to response was computed only for participants whose best response was PR or CR. |
| Median Duration of Response | Date of first PR or CR assessment to date of progression, death, or last tumor assessment (maximum participant duration of response of 25 weeks) | Duration of response was computed for participants whose best response was either PR or CR. Duration of overall response was defined as the period from the time that measurement criteria were first met for PR or CR, whichever was recorded first, until the first date of documented PD or death. Participants who neither relapsed nor died were to be censored on the date of their last tumor assessment. |
| Percentage of Participants Surviving at 1 Year | Date first participant enrolled to 1 year | One year survival rates were computed using Kaplan-Meier estimates. |
| Percentage of Participants With Progression-free Survival at Week 24 | Date of randomization to Week 24 | Week 24 Progression-free Survival was defined as the number of participants who neither progressed nor died before Week 24. Computed using Kaplan-Meier estimates, only at the time of Interim Analysis, when all participants had been followed for 6 months. |
| Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | At initiation of treatment and throughout study, to a minimum of 30 days after last dose of study drug. Laboratory tests performed within 72 hours before start of each cycle | CTC, Version 3 used to assess parameters. CTC Gr=Grade; WBC=white blood cells; ANC=absolute neutrophil count. LLN=lower level of normal. WBC Gr 1:\<LLN to 3.0\*10\^9/L, Gr 2:\<3.0 to 2.0\*10\^9/L, Gr 3:\<2.0 to 1.0\*10\^9/L, Gr 4:\<1.0\*10\^9/L; ANC Gr 1:\<LLN to 1.5\*10\^9/L, Gr 2:\<1.5 to 1.0\*10\^9/L, Gr 3:\<1.0 to 0.5\*10\^9/L, Gr 4:\<0.5\*10\^9/L; Platelet count Gr 1:LLN to 75.0\*10\^9/L, Gr 2:\<75.0 to 50.0\*10\^9/L, Gr 3:\<50.0 to 25.0\*10\^9/L, Gr 4:\<25.0 to 10\^9/L; Hemoglobin Gr 1:\<LLN to 10.0 g/dL, Gr 2:\<10.0 to 8.0 g/dL, Gr 3:\<8.0 to 6.5 g/dL, Gr 4:\<6.5 g/dL. |
| Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | At initiation of treatment and throughout study, to a minimum of 30 days after last dose of study drug. Laboratory tests performed within 72 hours before start of each cycle | ULN=Upper limit of normal.ALT Gr 1:\>ULN to 2.5\*ULN, Gr 2: \>2.5 to 5.0\*ULN, Gr 3: \>5.0 to 20.0\*ULN, Gr 4: \>20.0\*ULN; AST Gr 1: \>ULN to 2.5\*ULN, Gr 2: \>2.5 to 5.0\*ULN, Gr 3: \>5.0 to 20.0\*ULN, Gr 4: \>20.0\*ULN; ALP Gr 1:\>ULN to 2.5\*ULN, Gr 2: \>2.5 to 5.0\*ULN, Gr 3: \>5.0 to 20.0\*ULN, Gr 4: \>20.0\*ULN; Total bilirubin Gr 1: \>ULN to 1.5\*ULN, Gr 2: \>1.5 to 3.0\*ULN, Gr 3: \>3.0 to 10.0\*ULN, Gr 4: \>10.0\*ULN. |
| Number of Participants With Abnormalities in Renal Function by Worst CTC Grade | At initiation of treatment and throughout study, to a minimum of 30 days after last dose of study drug. Laboratory tests performed within 72 hours before start of each cycle | Creatine Gr 1: \>ULN to 1.5\*ULN, Gr 2: 1.5 to 3.0\*ULN, Gr 3: \>3.0 to 6.0\*ULN, Gr 4: \>6.0\*ULN. |
| Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs | At initiation of treatment throughout study, to a minimum of 30 days after last dose of study drug | An AE is any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, drug dependency or abuse; is life-threatening, an important medical event, a congenital anomaly/birth defect; requires inpatient hospitalization; or prolongs existing hospitalization. Treatment related=possibly, probably, or certainly related to and of unknown relationship to study treatment. |
| Median Progression-free Survival (PFS) | Date of randomization to date of progression, death, or last tumor assessment (maximum participant PFS of 29 months) | PFS was defined as the time from randomization to progression or to death from any cause without prior documentation of progression. Participants who did not progress or die were to be censored on the date of their last tumor assessment. |
Countries
France, Italy, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
Of the 136 participants enrolled in this study, 123 were randomized. Of the 13 not randomized, 11 no longer met study criteria, 1 withdrew, and 1 was found to have extensive disease. Of the 123 randomized, 122 were treated, and 1 no longer met study criteria and was never treated.
Participants by arm
| Arm | Count |
|---|---|
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg Ixabepilone,16 mg/m\^2, administered as a 1-hour intravenous (IV) infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered after ixabepilone as IV infusion every 2 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity. | 46 |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg Ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity After Cycle 4, dose reduction to 32 mg/m\^2 implemented for all subsequent cycles. Bevacizumab, 15 mg/kg, administered after ixabepilone as IV infusion every 3 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity. | 45 |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg Paclitaxel, 90 mg/m\^2, given as a 1-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered as IV infusion every 2 weeks. Bevacizumab infused over 90 minutes for the first dose, and if well tolerated, over 60 minutes for the second dose. If still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity. | 32 |
| Total | 123 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 2 |
| Overall Study | Disease progression | 23 | 23 | 15 |
| Overall Study | High risk of allergic reaction | 0 | 1 | 0 |
| Overall Study | Investigator decision | 2 | 1 | 0 |
| Overall Study | Maximum clinical benefit | 3 | 5 | 5 |
| Overall Study | Never treated | 1 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 1 | 0 |
| Overall Study | Planned radiation for palliation | 0 | 1 | 0 |
| Overall Study | Poor or noncompliance | 0 | 0 | 1 |
| Overall Study | Still on treatment | 1 | 3 | 2 |
| Overall Study | Study drug toxicity | 11 | 8 | 6 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Total |
|---|---|---|---|---|
| Age, Continuous | 60.0 years | 59.0 years | 59.0 years | 59.0 years |
| Age, Customized >=65 years | 13 participants | 16 participants | 10 participants | 39 participants |
| Age, Customized Younger than 65 years | 33 participants | 29 participants | 22 participants | 84 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 43 Participants | 40 Participants | 31 Participants | 114 Participants |
| Sex: Female, Male Female | 46 Participants | 45 Participants | 32 Participants | 123 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 45 / 45 | 45 / 45 | 32 / 32 |
| serious Total, serious adverse events | 15 / 45 | 16 / 45 | 9 / 32 |
Outcome results
Primary
Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST)
Best tumor response was assessed with RECIST. Complete response (CR)=Disappearance of all evidence of target lesions; Partial response (PR)=At least 30% reduction from baseline in the sum of the longest diameter (LD) of all target lesions; Progressive disease (PD)=At least a 20% increase from baseline in the sum of LD of target lesions or the appearance of 1 or more new lesions; Stable disease (SD)=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. A response was confirmed if noted on 2 examinations at least 4 weeks apart.
Time frame: Baseline visit and then every 8 weeks to 12 months, then every 3 months until disease progression
Population: All randomized participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) | Partial Response | 20 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) | Unable to Determine | 1 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) | Progressive Disease | 5 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) | Complete Response | 2 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) | Stable Disease | 18 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) | Complete Response | 2 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) | Partial Response | 30 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) | Stable Disease | 9 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) | Progressive Disease | 3 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) | Unable to Determine | 1 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) | Stable Disease | 11 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) | Complete Response | 4 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) | Unable to Determine | 1 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) | Partial Response | 16 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) | Progressive Disease | 0 Participants |
Primary
Percentage of Participants With Best Tumor Response of Partial Response (PR) or Complete Response (CR) While On-study
CR=Disappearance of all clinical and radiologic evidence of target lesions; PR=At least 30% reduction in the sum of the longest diameter of all target lesions.
Time frame: Baseline visit and then every 8 weeks to 12 months, then every 3 months until disease progression
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Percentage of Participants With Best Tumor Response of Partial Response (PR) or Complete Response (CR) While On-study | 47.8 Percentage of participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Percentage of Participants With Best Tumor Response of Partial Response (PR) or Complete Response (CR) While On-study | 71.1 Percentage of participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Percentage of Participants With Best Tumor Response of Partial Response (PR) or Complete Response (CR) While On-study | 62.5 Percentage of participants |
Secondary
Median Duration of Response
Duration of response was computed for participants whose best response was either PR or CR. Duration of overall response was defined as the period from the time that measurement criteria were first met for PR or CR, whichever was recorded first, until the first date of documented PD or death. Participants who neither relapsed nor died were to be censored on the date of their last tumor assessment.
Time frame: Date of first PR or CR assessment to date of progression, death, or last tumor assessment (maximum participant duration of response of 25 weeks)
Population: Participants whose best response was CR or PR, as assessed by the investigator.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Median Duration of Response | 10.1 Months |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Median Duration of Response | 10.3 Months |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Median Duration of Response | 13.1 Months |
Secondary
Median Progression-free Survival (PFS)
PFS was defined as the time from randomization to progression or to death from any cause without prior documentation of progression. Participants who did not progress or die were to be censored on the date of their last tumor assessment.
Time frame: Date of randomization to date of progression, death, or last tumor assessment (maximum participant PFS of 29 months)
Population: All randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Median Progression-free Survival (PFS) | 9.6 Months |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Median Progression-free Survival (PFS) | 11.9 Months |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Median Progression-free Survival (PFS) | 13.5 Months |
Secondary
Median Time to Response
Time to response was defined as the time from the first dose of study therapy until measurement criteria were first met for a PR or CR, whichever was recorded first. Time to response was computed only for participants whose best response was PR or CR.
Time frame: Date of first PR or CR assessment to date of progression, death, or last tumor assessment (maximum participant time to response of 67 weeks)
Population: Participants whose best response was CR or PR, as assessed by the investigator.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Median Time to Response | 8.2 Weeks |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Median Time to Response | 8.3 Weeks |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Median Time to Response | 8.1 Weeks |
Secondary
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade
CTC, Version 3 used to assess parameters. CTC Gr=Grade; WBC=white blood cells; ANC=absolute neutrophil count. LLN=lower level of normal. WBC Gr 1:\<LLN to 3.0\*10\^9/L, Gr 2:\<3.0 to 2.0\*10\^9/L, Gr 3:\<2.0 to 1.0\*10\^9/L, Gr 4:\<1.0\*10\^9/L; ANC Gr 1:\<LLN to 1.5\*10\^9/L, Gr 2:\<1.5 to 1.0\*10\^9/L, Gr 3:\<1.0 to 0.5\*10\^9/L, Gr 4:\<0.5\*10\^9/L; Platelet count Gr 1:LLN to 75.0\*10\^9/L, Gr 2:\<75.0 to 50.0\*10\^9/L, Gr 3:\<50.0 to 25.0\*10\^9/L, Gr 4:\<25.0 to 10\^9/L; Hemoglobin Gr 1:\<LLN to 10.0 g/dL, Gr 2:\<10.0 to 8.0 g/dL, Gr 3:\<8.0 to 6.5 g/dL, Gr 4:\<6.5 g/dL.
Time frame: At initiation of treatment and throughout study, to a minimum of 30 days after last dose of study drug. Laboratory tests performed within 72 hours before start of each cycle
Population: All randomized participants who received any study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Absolute neutrophil count (ANC) (Grade 1) | 10 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | WBC (Grade 2) | 14 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | WBC (Grade 3) | 1 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | WBC (Grade 4) | 2 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | White blood cells (WBC) (Grade 1) | 11 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | ANC (Grade 2) | 9 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | ANC (Grade 3) | 5 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | ANC (Grade 4) | 2 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Platelet count (Grade 1) | 4 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Platelet count (Grade 2) | 1 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Platelet count (Grade 3) | 0 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Platelet count (Grade 4) | 2 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Hemoglobin (Grade 1) | 21 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Hemoglobin (Grade 2) | 3 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Hemoglobin (Grade 3) | 1 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Hemoglobin (Grade 4) | 1 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | ANC (Grade 2) | 10 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | ANC (Grade 3) | 17 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | ANC (Grade 4) | 10 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Hemoglobin (Grade 2) | 4 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Platelet count (Grade 1) | 15 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Platelet count (Grade 2) | 1 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Hemoglobin (Grade 4) | 0 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Platelet count (Grade 3) | 0 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | White blood cells (WBC) (Grade 1) | 12 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Hemoglobin (Grade 3) | 3 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | WBC (Grade 2) | 12 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Platelet count (Grade 4) | 1 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | WBC (Grade 3) | 14 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | WBC (Grade 4) | 4 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Absolute neutrophil count (ANC) (Grade 1) | 4 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Hemoglobin (Grade 1) | 20 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Platelet count (Grade 3) | 0 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | ANC (Grade 2) | 13 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Hemoglobin (Grade 1) | 17 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | WBC (Grade 3) | 3 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | ANC (Grade 3) | 6 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Hemoglobin (Grade 4) | 0 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | White blood cells (WBC) (Grade 1) | 12 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | ANC (Grade 4) | 1 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Platelet count (Grade 4) | 0 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Absolute neutrophil count (ANC) (Grade 1) | 6 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Platelet count (Grade 1) | 3 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Hemoglobin (Grade 2) | 3 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | WBC (Grade 2) | 11 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Platelet count (Grade 2) | 0 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | WBC (Grade 4) | 0 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | Hemoglobin (Grade 3) | 2 Participants |
Secondary
Number of Participants With Abnormalities in Liver Function by Worst CTC Grade
ULN=Upper limit of normal.ALT Gr 1:\>ULN to 2.5\*ULN, Gr 2: \>2.5 to 5.0\*ULN, Gr 3: \>5.0 to 20.0\*ULN, Gr 4: \>20.0\*ULN; AST Gr 1: \>ULN to 2.5\*ULN, Gr 2: \>2.5 to 5.0\*ULN, Gr 3: \>5.0 to 20.0\*ULN, Gr 4: \>20.0\*ULN; ALP Gr 1:\>ULN to 2.5\*ULN, Gr 2: \>2.5 to 5.0\*ULN, Gr 3: \>5.0 to 20.0\*ULN, Gr 4: \>20.0\*ULN; Total bilirubin Gr 1: \>ULN to 1.5\*ULN, Gr 2: \>1.5 to 3.0\*ULN, Gr 3: \>3.0 to 10.0\*ULN, Gr 4: \>10.0\*ULN.
Time frame: At initiation of treatment and throughout study, to a minimum of 30 days after last dose of study drug. Laboratory tests performed within 72 hours before start of each cycle
Population: All randomized participants who received any study drug and had samples available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | Alanine aminotransferase (ALT) (Grade 1) | 18 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | ALT (Grade 4) | 0 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | ALT (Grade 2) | 2 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | ALT (Grade 3) | 1 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | AST (Grade 1) | 20 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | AST (Grade 2) | 1 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | AST (Grade 3) | 1 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | AST (Grade 4) | 0 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | Alkaline phosphatase (ALP) (Grade 1) | 8 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | ALP (Grade 2) | 0 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | ALP (Grade 3) | 0 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | ALP (Grade 4) | 0 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | Total bilirubin (Grade 1) | 3 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | Total bilirubin (Grade 2) | 2 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | Total bilirubin (Grade 3) | 0 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | Total bilirubin (Grade 4) | 0 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | AST (Grade 2) | 1 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | AST (Grade 3) | 0 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | AST (Grade 4) | 0 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | Total bilirubin (Grade 2) | 0 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | Alkaline phosphatase (ALP) (Grade 1) | 11 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | ALP (Grade 2) | 3 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | Total bilirubin (Grade 4) | 0 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | ALP (Grade 3) | 0 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | Alanine aminotransferase (ALT) (Grade 1) | 13 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | Total bilirubin (Grade 3) | 0 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | ALP (Grade 4) | 0 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | ALT (Grade 2) | 4 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | ALT (Grade 3) | 0 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | ALT (Grade 4) | 0 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | AST (Grade 1) | 18 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | Total bilirubin (Grade 1) | 3 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | ALP (Grade 3) | 1 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | AST (Grade 2) | 1 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | Total bilirubin (Grade 1) | 2 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | Total bilirubin (Grade 3) | 0 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | AST (Grade 3) | 0 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | Total bilirubin (Grade 4) | 0 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | ALT (Grade 3) | 0 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | AST (Grade 4) | 0 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | Alanine aminotransferase (ALT) (Grade 1) | 13 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | AST (Grade 1) | 15 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | Alkaline phosphatase (ALP) (Grade 1) | 12 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | Total bilirubin (Grade 2) | 1 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | ALT (Grade 4) | 0 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | ALP (Grade 2) | 0 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | ALT (Grade 2) | 3 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Liver Function by Worst CTC Grade | ALP (Grade 4) | 0 Participants |
Secondary
Number of Participants With Abnormalities in Renal Function by Worst CTC Grade
Creatine Gr 1: \>ULN to 1.5\*ULN, Gr 2: 1.5 to 3.0\*ULN, Gr 3: \>3.0 to 6.0\*ULN, Gr 4: \>6.0\*ULN.
Time frame: At initiation of treatment and throughout study, to a minimum of 30 days after last dose of study drug. Laboratory tests performed within 72 hours before start of each cycle
Population: All randomized participants who received any study drug and had samples available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Renal Function by Worst CTC Grade | Creatinine (Grade 2) | 3 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Renal Function by Worst CTC Grade | Creatinine (Grade 1) | 5 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Renal Function by Worst CTC Grade | Creatinine (Grade 3) | 0 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Renal Function by Worst CTC Grade | Creatinine (Grade 4) | 0 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Renal Function by Worst CTC Grade | Creatinine (Grade 4) | 0 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Renal Function by Worst CTC Grade | Creatinine (Grade 3) | 0 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Renal Function by Worst CTC Grade | Creatinine (Grade 1) | 3 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Abnormalities in Renal Function by Worst CTC Grade | Creatinine (Grade 2) | 1 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Renal Function by Worst CTC Grade | Creatinine (Grade 1) | 3 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Renal Function by Worst CTC Grade | Creatinine (Grade 2) | 0 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Renal Function by Worst CTC Grade | Creatinine (Grade 3) | 0 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Abnormalities in Renal Function by Worst CTC Grade | Creatinine (Grade 4) | 0 Participants |
Secondary
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs
An AE is any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, drug dependency or abuse; is life-threatening, an important medical event, a congenital anomaly/birth defect; requires inpatient hospitalization; or prolongs existing hospitalization. Treatment related=possibly, probably, or certainly related to and of unknown relationship to study treatment.
Time frame: At initiation of treatment throughout study, to a minimum of 30 days after last dose of study drug
Population: All randomized participants who received any study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs | Deaths | 12 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs | SAEs | 15 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs | Treatment-related SAEs | 7 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs | Treatment-related AEs Leading to Discontinuation | 24 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs | AEs Leading to Discontinuation | 26 Participants |
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs | Treatment-related AEs | 43 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs | Treatment-related AEs | 45 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs | Deaths | 15 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs | Treatment-related AEs Leading to Discontinuation | 23 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs | AEs Leading to Discontinuation | 25 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs | SAEs | 16 Participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs | Treatment-related SAEs | 9 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs | SAEs | 9 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs | Treatment-related SAEs | 5 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs | Treatment-related AEs | 32 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs | Treatment-related AEs Leading to Discontinuation | 20 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs | Deaths | 5 Participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) Treatment-related SAEs, Treatment-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, Treatment-related AEs | AEs Leading to Discontinuation | 21 Participants |
Secondary
Percentage of Participants Surviving at 1 Year
One year survival rates were computed using Kaplan-Meier estimates.
Time frame: Date first participant enrolled to 1 year
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Percentage of Participants Surviving at 1 Year | 91 Percentage of participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Percentage of Participants Surviving at 1 Year | 89 Percentage of participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Percentage of Participants Surviving at 1 Year | 91 Percentage of participants |
Secondary
Percentage of Participants With Progression-free Survival at Week 24
Week 24 Progression-free Survival was defined as the number of participants who neither progressed nor died before Week 24. Computed using Kaplan-Meier estimates, only at the time of Interim Analysis, when all participants had been followed for 6 months.
Time frame: Date of randomization to Week 24
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg | Percentage of Participants With Progression-free Survival at Week 24 | 75 Percentage of participants |
| Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg | Percentage of Participants With Progression-free Survival at Week 24 | 86 Percentage of participants |
| Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg | Percentage of Participants With Progression-free Survival at Week 24 | 94 Percentage of participants |