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Paclitaxel, Nab-paclitaxel, or Ixabepilone With or Without Bevacizumab in Treating Patients With Stage IIIC or Stage IV Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00785291
Recruitment Status : Completed
First Posted : November 5, 2008
Results First Posted : July 2, 2015
Last Update Posted : October 10, 2022
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Description
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Brief Summary:
This randomized phase III trial studies the side effects and how well different chemotherapy regimens with or without bevacizumab work in treating patients with stage IIIC or stage IV breast cancer. Drugs used in chemotherapy, such as paclitaxel, paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel), and ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bevacizumab may block tumor growth by targeting certain cells and slowing the growth of blood vessels to the tumor. It is not yet known which treatment regimen is more effective in treating patients with breast cancer.

Condition or disease Intervention/treatment Phase
Estrogen Receptor Negative Estrogen Receptor Positive HER2/Neu Negative HER2/Neu Positive Progesterone Receptor Negative Progesterone Receptor Positive Recurrent Breast Carcinoma Stage IIIC Breast Cancer AJCC v6 Stage IV Breast Cancer AJCC v6 and v7 Biological: Bevacizumab Drug: Ixabepilone Other: Laboratory Biomarker Analysis Drug: Nab-paclitaxel Drug: Paclitaxel Other: Questionnaire Administration Phase 3

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Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 799 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase III Trial of Weekly Paclitaxel Compared to Weekly Nanoparticle Albumin Bound Nab-paclitaxel or Ixabepilone With or Without Bevacizumab as First-Line Therapy for Locally Recurrent or Metastatic Breast Cancer
Actual Study Start Date : October 13, 2008
Actual Primary Completion Date : December 31, 2013
Actual Study Completion Date : June 15, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Arm A (Paclitaxel)
Patients receive 90 mg/m^2 paclitaxel IV over 1 hour on days 1, 8, and 15. Patients may receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15.
 Biological: Bevacizumab
Given IV
Other Names:
  • ABP 215
  • Anti-VEGF
  • Anti-VEGF Humanized Monoclonal Antibody
  • Anti-VEGF Monoclonal Antibody SIBP04
  • Anti-VEGF rhuMAb
  • Avastin
  • Bevacizumab awwb
  • Bevacizumab Biosimilar ABP 215
  • Bevacizumab Biosimilar BEVZ92
  • Bevacizumab Biosimilar BI 695502
  • Bevacizumab Biosimilar CBT 124
  • Bevacizumab Biosimilar CT-P16
  • Bevacizumab Biosimilar FKB238
  • Bevacizumab Biosimilar GB-222
  • Bevacizumab Biosimilar HD204
  • Bevacizumab Biosimilar HLX04
  • Bevacizumab Biosimilar IBI305
  • Bevacizumab Biosimilar LY01008
  • Bevacizumab Biosimilar MIL60
  • Bevacizumab Biosimilar Mvasi
  • Bevacizumab Biosimilar MYL-1402O
  • Bevacizumab Biosimilar QL 1101
  • Bevacizumab Biosimilar RPH-001
  • Bevacizumab Biosimilar SCT501
  • Bevacizumab Biosimilar Zirabev
  • Bevacizumab-awwb
  • Bevacizumab-bvzr
  • BP102
  • BP102 Biosimilar
  • HD204
  • Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer
  • Mvasi
  • MYL-1402O
  • Recombinant Humanized Anti-VEGF Monoclonal Antibody
  • rhuMab-VEGF
  • SCT501
  • SIBP 04
  • SIBP-04
  • SIBP04
  • Zirabev

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Other: Questionnaire Administration
Ancillary studies
Experimental: Arm B (Nab-paclitaxel)
Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Patients may also receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15.
 Biological: Bevacizumab
Given IV
Other Names:
  • ABP 215
  • Anti-VEGF
  • Anti-VEGF Humanized Monoclonal Antibody
  • Anti-VEGF Monoclonal Antibody SIBP04
  • Anti-VEGF rhuMAb
  • Avastin
  • Bevacizumab awwb
  • Bevacizumab Biosimilar ABP 215
  • Bevacizumab Biosimilar BEVZ92
  • Bevacizumab Biosimilar BI 695502
  • Bevacizumab Biosimilar CBT 124
  • Bevacizumab Biosimilar CT-P16
  • Bevacizumab Biosimilar FKB238
  • Bevacizumab Biosimilar GB-222
  • Bevacizumab Biosimilar HD204
  • Bevacizumab Biosimilar HLX04
  • Bevacizumab Biosimilar IBI305
  • Bevacizumab Biosimilar LY01008
  • Bevacizumab Biosimilar MIL60
  • Bevacizumab Biosimilar Mvasi
  • Bevacizumab Biosimilar MYL-1402O
  • Bevacizumab Biosimilar QL 1101
  • Bevacizumab Biosimilar RPH-001
  • Bevacizumab Biosimilar SCT501
  • Bevacizumab Biosimilar Zirabev
  • Bevacizumab-awwb
  • Bevacizumab-bvzr
  • BP102
  • BP102 Biosimilar
  • HD204
  • Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer
  • Mvasi
  • MYL-1402O
  • Recombinant Humanized Anti-VEGF Monoclonal Antibody
  • rhuMab-VEGF
  • SCT501
  • SIBP 04
  • SIBP-04
  • SIBP04
  • Zirabev

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Nab-paclitaxel
Given IV
Other Names:
  • ABI 007
  • ABI-007
  • Abraxane
  • Albumin-bound Paclitaxel
  • Albumin-Stabilized Nanoparticle Paclitaxel
  • Nanoparticle Albumin-bound Paclitaxel
  • Nanoparticle Paclitaxel
  • Paclitaxel Albumin
  • paclitaxel albumin-stabilized nanoparticle formulation
  • Protein-bound Paclitaxel

Other: Questionnaire Administration
Ancillary studies
Experimental: Arm C (Ixabepilone)
Patients receive ixabepilone IV over 60 minutes on days 1, 8, and 15. Patients may also receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. (closed to accrual as of 7/18/11)
 Biological: Bevacizumab
Given IV
Other Names:
  • ABP 215
  • Anti-VEGF
  • Anti-VEGF Humanized Monoclonal Antibody
  • Anti-VEGF Monoclonal Antibody SIBP04
  • Anti-VEGF rhuMAb
  • Avastin
  • Bevacizumab awwb
  • Bevacizumab Biosimilar ABP 215
  • Bevacizumab Biosimilar BEVZ92
  • Bevacizumab Biosimilar BI 695502
  • Bevacizumab Biosimilar CBT 124
  • Bevacizumab Biosimilar CT-P16
  • Bevacizumab Biosimilar FKB238
  • Bevacizumab Biosimilar GB-222
  • Bevacizumab Biosimilar HD204
  • Bevacizumab Biosimilar HLX04
  • Bevacizumab Biosimilar IBI305
  • Bevacizumab Biosimilar LY01008
  • Bevacizumab Biosimilar MIL60
  • Bevacizumab Biosimilar Mvasi
  • Bevacizumab Biosimilar MYL-1402O
  • Bevacizumab Biosimilar QL 1101
  • Bevacizumab Biosimilar RPH-001
  • Bevacizumab Biosimilar SCT501
  • Bevacizumab Biosimilar Zirabev
  • Bevacizumab-awwb
  • Bevacizumab-bvzr
  • BP102
  • BP102 Biosimilar
  • HD204
  • Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer
  • Mvasi
  • MYL-1402O
  • Recombinant Humanized Anti-VEGF Monoclonal Antibody
  • rhuMab-VEGF
  • SCT501
  • SIBP 04
  • SIBP-04
  • SIBP04
  • Zirabev

Drug: Ixabepilone
Given IV
Other Names:
  • (1S,3S,7S,10R,11S,12S,16R)-7,11-Dihydroxy-8,8,10,12,16-pentamethyl-3-[(1E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-17-oxa-4-azabicyclo[14.1.0]heptadecane-5,9-dione
  • Azaepothilone B
  • BMS 247550
  • BMS-247550
  • BMS247550
  • Epothilone
  • Epothilone-B BMS 247550
  • Ixempra

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Questionnaire Administration
Ancillary studies


Outcome Measures
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Primary Outcome Measures :
  1. Progression Free Survival [ Time Frame: Time from randomization to progression or death due to any cause, whichever occurs first (up to 5 years) ]
    Progression-free survival (PFS) is defined as the interval from registration until first disease progression, regardless of site, or death resulting from any cause, which ever occurred first. Distribution was estimated using the Kaplan Meier product-limit method. Progression is defined as a 20% increase in the sum of longest diameter of target lesions (per Response Evaluation Criteria in Solid Tumors [RECIST] criteria).


Secondary Outcome Measures :
  1. Objective Tumor Response Rate [ Time Frame: Up to 5 years ]
    Response was defined by the Response Evaluation Criteria in Solid Tumors (RECIST). A responding participant had either a Complete Response (disappearance of all target lesions) or Partial Response (30% decrease in sum of longest diameter of target lesions).

  2. Time to Treatment Failure [ Time Frame: Time from randomization until progression, death, or yearly termination of protocol therapy (up to 5 years) ]
    Time from registration until treatment failure, defined as early termination of protocol therapy for any reason, first disease progression or death without progression. Surviving participants who were failure free were censored as date last known alive and failure free. Distribution was estimated using the Kaplan Meier product-limit method.

  3. 12 Month Progression Free Survival [ Time Frame: 12 months ]
    Percentage of participants who were alive and progression free at 12 months. The 12 month progression free survival, with 95% confidence interval, was estimated using the Kaplan Meier method.

  4. Overall Survival [ Time Frame: Time from randomization to death or last follow-up (up to 5 years) ]
    Overall survival was measured as the interval from study entry until death, from any cause, or last contact. Distribution was estimated using the Kaplan Meier product-limit method.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic confirmation of invasive cancer of the breast
  • Stage IV disease or stage IIIC disease (using American Joint Committee on Cancer [AJCC] criteria, 6th edition) not amenable to local therapy
  • Patients may not have a "currently active" second malignancy other than non-melanoma skin cancers; patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse
  • Patients with human epidermal growth factor receptor 2 (HER2) negative disease are eligible; patients with HER2+ disease are eligible providing they have previously received trastuzumab or lapatinib; documentation of progression on HER2 directed therapy is not required; Her2/neu status must be known at the time of protocol registration
  • Estrogen receptor (ER) and progesterone receptor (PgR) status must be known at the time of registration; ER and/or PgR >= 1% cells will be considered positive
  • Prior treatment may include adjuvant or neoadjuvant taxane, however, the interval between completion of adjuvant or neoadjuvant therapy and disease recurrence must be >= 12 months
  • No prior chemotherapy for metastatic breast cancer
  • Any number of prior hormonal therapies are allowed; the last dose should have been administered at least 7 days prior to the initiation of protocol therapy
  • Prior radiotherapy must be completed at least 2 weeks prior to study entry
  • Treatment with bisphosphonates is allowed and recommended as per American Society of Clinical Oncology (ASCO) guidelines
  • Prior trastuzumab or lapatinib required for patients with HER2 overexpressing tumors
  • Prior treatment with bevacizumab is allowed

  • Patients must not have had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study registration, and must have fully recovered from any such procedure

    • The following are not considered to be major procedures: thoracentesis, paracentesis, port placement, laparoscopy, thoracoscopy, bronchoscopy, endoscopic ultrasonographic procedures, mediastinoscopy, skin biopsies, incisional biopsies and routine dental procedures
  • Patients must not have anticipation of need for a major surgical procedure during the course of the study

  • There are no restrictions on core biopsies, placement of a vascular access device or other minor procedures prior to registration

    • Placement of a vascular access device after starting study therapy should be performed between day 15 and 28 of a treatment cycle (but not less than 48 hours before the next dose of bevacizumab) to allow for sufficient healing

  • Patients must have measurable disease (target lesions): measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 2.0 cm with conventional techniques or as >= 1 cm with spiral computed tomography (CT) scan

    • Lesions that are considered non-measurable include the following:

      • Bone lesions
      • Leptomeningeal disease
      • Ascites
      • Pleural/pericardial effusion
      • Inflammatory breast disease
      • Lymphangitis cutis/pulmonitis
      • Abdominal masses that are not confirmed and followed by imaging techniques
      • Cystic lesions
  • Patients with pre-existing peripheral neuropathy >= grade 2 are not eligible for this study
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status of =< 1 to be eligible for this trial
  • Women must not be pregnant or breast feeding; premenopausal women must have a negative serum or urine beta-human chorionic gonadotropin (Hcg)
  • Patients with a history of Common Terminology Criteria for Adverse Events (CTCAE) grade >= 3 hypersensitivity to paclitaxel or Cremophor® EL are not eligible
  • Patients with a history of abdominal fistula, or intra-abdominal abscess within 6 months prior to study registration are not eligible
  • Patients with a history of gastrointestinal (GI) perforation within 12 months prior to registration are not eligible
  • Patients with a history of significant bleeding episodes (e.g., hemoptysis, upper or lower GI bleeding) within 6 months prior to registration are not eligible

  • Patients must not have a history of clinically significant cardiovascular disease that includes the following:

    • Uncontrolled hypertension defined as systolic blood pressure > 150 and/or diastolic blood pressure > 90 mmHg on antihypertensive medications or any prior history of hypertensive crisis or hypertensive encephalopathy
    • History of myocardial infarction or unstable angina within past 6 months
    • New York Heart Association (NYHA) congestive heart failure grade 2 or greater
    • Symptomatic peripheral vascular disease
    • Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or arterial thrombotic events
  • Patients on full dose anticoagulants must be on a stable dose of warfarin, or be on a stable dose of low molecular weight (LMW) heparin; patients receiving anti-platelet or on daily prophylactic dose aspirin are eligible, as are patients receiving stable doses of anticoagulation for atrial fibrillation
  • Patients may not have a history of stroke or transient ischemic attack within 6 months prior to study registration
  • Patients with a history of seizures must be well controlled with standard medication
  • Patients must not have progressing or untreated central nervous system (CNS) metastases or leptomeningeal disease; patients with a history of resected brain metastases with stable magnetic resonance imaging (MRI) scans for 3 months including within 4 weeks of study start are eligible; patients with a history of gamma knife radiosurgery or whole brain radiation with stable MRI scans for 3 months including within 4 weeks of study start are eligible
  • No serious, non-healing wound, ulcer or bone fracture
  • Life expectancy of >= 12 weeks
  • Granulocytes >= 1,500/ul
  • Platelet count >= 100,000/ul
  • Creatinine =< 2.0 mg/dL
  • Bilirubin < 1.5 mg/dL (unless due to Gilbert's syndrome)
  • Transaminases (aspartate aminotransferase [AST], alanine aminotransferase [ALT]) =< 2.5 x upper limit of normal (ULN)
  • Serum or urine beta-Hcg negative in premenopausal women of child-bearing potential

  • Urine protein =< 1+ protein* or urine protein: creatinine ratio (UPC) < 1

    • Patients discovered to have >= 2+ proteinuria at baseline must undergo a 24-hour urine collection that must demonstrate < 1 g of protein/24 hr or UPC ratio =< 1 to allow participation in the study
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00785291


Locations
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Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Hope S Rugo Alliance for Clinical Trials in Oncology
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00785291    
Other Study ID Numbers: NCI-2009-00476
NCI-2009-00476 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CTSU 40502
CDR0000617539
NCCTG N063H
CALGB-40502
PCALGB-40502_A11PAMDREVW01
CALGB 40502 ( Other Identifier: Alliance for Clinical Trials in Oncology )
CALGB-40502 ( Other Identifier: CTEP )
U10CA180821 ( U.S. NIH Grant/Contract )
U10CA031946 ( U.S. NIH Grant/Contract )
First Posted: November 5, 2008    Key Record Dates
Results First Posted: July 2, 2015
Last Update Posted: October 10, 2022
Last Verified: October 2022
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Epothilones
Epothilone B
Albumin-Bound Paclitaxel
Bevacizumab
Antineoplastic Agents, Immunological
Endothelial Growth Factors
Antibodies
Immunoglobulins
 Antibodies, Monoclonal
Immunoglobulin G
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Immunologic Factors