Clinical trial NCT00370552: A Trial of 2 Schedules of Ixabepilone Plus Bevacizumab and Paclitaxel Plus Bevacizumab for Breast Cancer
Official title: A Phase II Open Label, Randomized, 3 Arm Trial of 2 Schedules of Ixabepilone Plus Bevacizumab and Paclitaxel Plus Bevacizumab as First Line Therapy for Locally Recurrent or Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Lead sponsor: R-Pharm
Sponsor class: INDUSTRY
First posted: 2006-08-31
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Best Tumor Response of Partial Response (PR) or Complete Response (CR) While On-study
timeFrame: Baseline visit and then every 8 weeks to 12 months, then every 3 months until disease progression
measure: Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Baseline visit and then every 8 weeks to 12 months, then every 3 months until disease progression
Secondary outcomes:
measure: Percentage of Participants With Progression-free Survival at Week 24
timeFrame: Date of randomization to Week 24
measure: Median Progression-free Survival (PFS)
timeFrame: Date of randomization to date of progression, death, or last tumor assessment (maximum participant PFS of 29 months)
measure: Median Time to Response
timeFrame: Date of first PR or CR assessment to date of progression, death, or last tumor assessment (maximum participant time to response of 67 weeks)
measure: Median Duration of Response
timeFrame: Date of first PR or CR assessment to date of progression, death, or last tumor assessment (maximum participant duration of response of 25 weeks)
measure: Percentage of Participants Surviving at 1 Year
timeFrame: Date first participant enrolled to 1 year
measure: 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
timeFrame: At initiation of treatment throughout study, to a minimum of 30 days after last dose of study drug
measure: Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade
timeFrame: 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
measure: Number of Participants With Abnormalities in Liver Function by Worst CTC Grade
timeFrame: 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
measure: Number of Participants With Abnormalities in Renal Function by Worst CTC Grade
timeFrame: 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
Other outcomes:
Locations:
city: Burbank
country: United States
facility: East Valley Hematology And Oncology Medical Group
state: California
city: La Verne
country: United States
facility: Wilshire Oncology Medical Group, Inc.
state: California
city: San Francisco
country: United States
facility: Ucsf-Comprehensive Cancer Center
state: California
city: Iowa City
country: United States
facility: University Of Iowa Hospitals And Clinics
state: Iowa
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center
state: Missouri
city: New York
country: United States
facility: Weill Medical College Of Cornell University
state: New York
city: Besancon Cedex
country: France
facility: Local Institution
city: Clermont-Ferrand
country: France
facility: Local Institution
city: Marseille Cedex 9
country: France
facility: Local Institution
city: Paris Cedex 10
country: France
facility: Local Institution
city: Saint Herblain
country: France
facility: Local Institution
city: Strasbourg Cedex
country: France
facility: Local Institution
city: Tours Cedex
country: France
facility: Local Institution
city: Cuneo
country: Italy
facility: Local Institution
city: Meldola Fc
country: Italy
facility: Local Institution
city: Milano
country: Italy
facility: Local Institution
city: Modena
country: Italy
facility: Local Institution
city: Napoli
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Hospitalet De Llobregat
country: Spain
facility: Local Institution
city: Jaen
country: Spain
facility: Local Institution
city: Chelmsford
country: United Kingdom
facility: Local Institution
state: Essex
city: Manchester
country: United Kingdom
facility: Local Institution
state: Greater Manchester
city: Nottingham
country: United Kingdom
facility: Local Institution
state: Nottinghamshire
city: Merseyside
country: United Kingdom
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: