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Bevacizumab and Paclitaxel, Paclitaxel Albumin-Stabilized Nanoparticle Formulation, or Ixabepilone in Treating Patients With Stage IIIC or Stage IV Breast Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), February 2010
First Received: November 4, 2008   Last Updated: February 6, 2010   History of Changes
Sponsor: Cancer and Leukemia Group B
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00785291
  Purpose

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as paclitaxel, paclitaxel albumin-stabilized nanoparticle formulation, and ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known which treatment regimen is more effective in treating patients with breast cancer.

PURPOSE: This randomized phase III trial is studying bevacizumab to see how well it works when given together with paclitaxel, paclitaxel albumin-stabilized nanoparticle formulation, or ixabepilone in treating patients with stage IIIC or stage IV breast cancer.


Condition Intervention Phase
Breast Cancer
Biological: bevacizumab
Drug: ixabepilone
Drug: paclitaxel
Drug: paclitaxel albumin-stabilized nanoparticle formulation
Phase III

Study Type: Interventional
Study Design: Treatment, Randomized
Official Title: A Randomized Phase III Trial of Weekly Paclitaxel Compared to Weekly Nanoparticle Albumin Bound NAB-Paclitaxel or Ixabepilone Combined With Bevacizumab as First-Line Therapy for Locally Recurrent or Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective tumor response as assessed by RECIST criteria [ Designated as safety issue: No ]
  • Duration of tumor response [ Designated as safety issue: No ]
  • Time to treatment failure [ Designated as safety issue: No ]
  • Probability of being progression-free at 12 months [ Designated as safety issue: No ]
  • Treatment-related toxicity as assessed by CTCAE version 3.0 [ Designated as safety issue: Yes ]
  • Overall survival [ Designated as safety issue: No ]

Estimated Enrollment: 900
Study Start Date: October 2008
Estimated Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm I: Active Comparator
Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Biological: bevacizumab
Given IV
Drug: paclitaxel
Given IV
Arm II: Experimental
Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Biological: bevacizumab
Given IV
Drug: paclitaxel albumin-stabilized nanoparticle formulation
Given IV
Arm III: Experimental
Patients receive ixabepilone IV over 60 minutes on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Biological: bevacizumab
Given IV
Drug: ixabepilone
Given IV

Detailed Description:

OBJECTIVES:

Primary

  • To compare the progression-free survival of patients with stage IIIC or IV breast cancer treated with paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel) versus ixabepilone versus paclitaxel with concurrent bevacizumab.

Secondary

  • To compare the objective response rate, duration of response, and time to treatment failure in patients receiving nab-paclitaxel versus paclitaxel, and to separately compare these endpoints in patients receiving ixabepilone versus paclitaxel.
  • To compare the 12-month rate of progression in patients treated with these regimens.
  • To compare treatment-related toxicities in patients receiving these regimens, according to the rates of grade 3/4 sensory neuropathy and the rates of peripheral neuropathy assessed by the FACT/GOG neurotoxicity subscale.
  • To compare overall survival of patients receiving these regimens.
  • To prospectively collect data on sociodemographics, non-cancer morbidities, and receipt of post-trial therapy to evaluate the role of potential disparities on survival from cancer.
  • To evaluate the relationship between physical activity behaviors at the time of study enrollment and progression-free and overall survival.

OUTLINE: This is a multicenter study. Patients are stratified according to taxane as adjuvant therapy (yes or no) and estrogen receptor (ER) or progesterone receptor (PgR) status (ER-positive or PgR-positive vs both ER-negative and PgR-negative). Patients are randomized to 1 of 3 treatment arms.

  • Arm I (weekly paclitaxel): Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15.
  • Arm II (weekly paclitaxel albumin-stabilized nanoparticle formulation [nab-paclitaxel]): Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15 and bevacizumab as in arm I.
  • Arm III (weekly ixabepilone): Patients receive ixabepilone IV over 60 minutes on days 1, 8, and 15 and bevacizumab as in arm I.

In all arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients complete questionnaires about peripheral neuropathy at baseline and before each course of therapy. They also complete questionnaires about sociodemographics, non-cancer comorbidities, social support, physical activity, and post-trial therapy at baseline and periodically thereafter.

After completion of study therapy, patients are followed every 6 months for 2 years and then annually for up to 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed invasive breast cancer

    • Stage IIIC or IV (locally recurrent or metastatic) disease not amenable to local therapy
  • Measurable disease (target lesions), defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 2.0 cm with conventional techniques or as ≥ 1 cm with spiral CT scan
  • No non-measurable lesions, including any of the following:

    • Ascites
    • Pleural/pericardial effusion
    • Inflammatory breast disease
    • Lymphangitis cutis/pulmonitis
    • Bone lesions
    • Leptomeningeal disease
    • Cystic lesions
    • Abdominal masses not confirmed and followed by imaging techniques
  • HER2/neu status must be known

    • HER2-positive disease allowed provided patient received prior trastuzumab (Herceptin®) or lapatinib (documentation of progression on HER2-directed therapy is not required)
  • No progressing or untreated CNS metastases or leptomeningeal disease

    • History of resected brain metastases with stable MRI scans for 3 months, including within the past 4 weeks allowed
    • History of gamma-knife radiosurgery or whole-brain radiation with stable MRI scans for 3 months, including within the past 4 weeks allowed
  • Hormone receptor status must be known

    • Estrogen receptor (ER)- and progesterone receptor (PgR)-positive if ≥ 1% cells are positive

PATIENT CHARACTERISTICS:

  • Menopausal status not specified
  • ECOG (Zubrod) performance status 0-1
  • Life expectancy ≥ 12 weeks
  • Granulocytes ≥ 1,500/μL
  • Platelet count ≥ 100,000/μL
  • Creatinine ≤ 2.0 mg/dL
  • Bilirubin < 1.5 mg/dL (unless due to Gilbert's syndrome)
  • AST and ALT ≤ 2.5 times upper limit of normal
  • Urine protein ≤ 1+ OR urine protein:creatinine ratio < 1

    • Patients with proteinuria ≥ 2+ at baseline must undergo a 24-hour urine collection that demonstrates < 1 g of protein/24 hr or UPC ratio ≤ 1
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • History of seizures allowed if well controlled with standard medication
  • No history of hypersensitivity to paclitaxel or Cremophor® EL CTCAE grade ≥ 3
  • No other active malignancy except nonmelanoma skin cancer (patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to have less than 30% risk of relapse)
  • No history of abdominal fistula or intra-abdominal abscess within 6 months prior to study registration
  • No history of gastrointestinal (GI) perforation within the past 12 months
  • No history of significant bleeding episodes (e.g., hemoptysis, upper or lower GI bleeding) within the past 6 months
  • No history of stroke or transient ischemic attack within the past 6 months
  • No history of clinically significant cardiovascular disease including any of the following:

    • Uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg and/or diastolic BP > 90 mm Hg on antihypertensive medications
    • Prior history of hypersensitivity or hypertensive encephalopathy
    • History of myocardial infarction or unstable angina within past 6 months
    • NYHA congestive heart failure class II-IV
    • Symptomatic peripheral vascular disease
    • Significant vascular disease (e.g., aortic aneurysm or aortic dissection) or arterial thrombotic events
  • No serious, non-healing wound, ulcer, or bone fracture
  • No significant traumatic injury in the past 28 days
  • No peripheral neuropathy ≥ grade 2

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior chemotherapy regimen for metastatic or locally advanced breast cancer
  • Adjuvant or neoadjuvant taxane allowed provided interval between completion of adjuvant therapy and disease recurrence is ≥ 12 months
  • At least 2 weeks since prior radiotherapy
  • At least 28 days since prior major surgical procedure or open biopsy and fully recovered
  • At least 7 days since prior core biopsy or other minor surgical procedure

    • Vascular access device placement allowed
  • At least 7 days since prior hormonal therapy

    • Any number of prior hormonal therapies allowed
  • Prior trastuzumab or lapatinib ditosylate for HER2-overexpressing tumors allowed
  • Prior bevacizumab allowed
  • Prior and concurrent bisphosphonate treatment allowed
  • No concurrent major surgical procedure
  • No concurrent palliative radiotherapy
  • No concurrent aprepitant
  • No concurrent pegfilgrastim
  • No other concurrent chemotherapy or anticancer hormone therapy
  • Concurrent full-dose anticoagulants allowed but patient must be on a stable dose of warfarin or low molecular weight heparin

    • Anti-platelet therapy or on daily prophylactic-dose aspirin allowed
    • Stable doses of anticoagulation for atrial fibrillation allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00785291

  Show 413 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
Investigators
Study Chair: Hope S. Rugo, MD University of California, San Francisco
Investigator: Alan P. Lyss, MD CCOP - Heartland Research Consortium
Investigator: Alvaro Moreno Aspitia, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Cancer and Leukemia Group B ( Richard L. Schilsky )
Study ID Numbers: CDR0000617539, CALGB-40502
Study First Received: November 4, 2008
Last Updated: February 6, 2010
ClinicalTrials.gov Identifier: NCT00785291     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
male breast cancer
recurrent breast cancer
stage IIIC breast cancer
stage IV breast cancer

Additional relevant MeSH terms:
Skin Diseases
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Growth Substances
Epothilones
Physiological Effects of Drugs
Mitosis Modulators
Breast Neoplasms
Bevacizumab
Antimitotic Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Paclitaxel
Therapeutic Uses
Tubulin Modulators
Growth Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents, Phytogenic
Breast Diseases

ClinicalTrials.gov processed this record on February 08, 2010