Clinical Trials (PDQ®)
|Phase III||Biomarker/Laboratory analysis, Treatment||Closed||18 and over||NCI||NCI-2009-00476|
CDR0000617539, CALGB 40502, U10CA031946, P30CA014236, NCT00785291
This randomized phase III trial is studying different chemotherapy regimens with or without bevacizumab and their side effects and comparing how well they work in treating patients with stage IIIC or stage IV breast cancer. 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. 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. It is not yet known which treatment regimen is more effective in treating patients with breast cancer.
Further Study Information
I. 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 or without bevacizumab.
I. 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.
II. To compare the 12-month rate of progression in patients treated with these regimens.
III. 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.
IV. To compare overall survival of patients receiving these regimens. V. 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.
VI. To evaluate the relationships between SPARC overexpression and changes in blood levels of caveolin-1 (Cav-1) to PFS and secondary endpoints of response during treatment in these patients.
V. To evaluate the relationships between changes in blood levels of circulating tumor cells (CTCs) and circulating endothelial cells (CECs) to PFS and secondary endpoints of response during treatment in these patients.
VII. To evaluate the association of expression levels of the microtubule associated proteins tau and beta-tubulin isotype composition with PFS and secondary endpoints of response during treatment.
VIII. To investigate a potential CYP2C8*2/*3 by paclitaxel interaction with respect to progression-free survival (PFS).
IX. To determine if CYP2C8*2 and CPY2C8*3 are associated with paclitaxel-induced peripheral neuropathy.
X. To perform exploratory analysis of CYP3A4, CYP3A5, ABCB1 and ABCC2 polymorphisms with response and toxicity profiles.
XI. 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.
XII. To evaluate the relationship between physical activity behaviors at the time of study enrollment and progression-free and overall survival.
XIII. To identify baseline factors that predict the risk of grade 3, 4, or 5 toxicity in patients receiving treatment with weekly paclitaxel, nab-paclitaxel, or ixabepilone combined with or without bevacizumab.
XIV. To perform an exploratory analysis of whether other factors included in patient assessments (either individually or in combination) predict the risk of grade 3, 4, or 5 toxicity in patients receiving weekly paclitaxel, nab-paclitaxel, or ixabepilone combined with or without bevacizumab, with a specific focus on the relationship between pre-existing hypertension or neuropathy. (Exploratory) XV. To compare the associations of baseline factors to grade 3, 4, or 5 toxicity in patients receiving weekly paclitaxel, nab-paclitaxel, or ixabepilone combined with or without bevacizumab.
XVI. To explore whether longitudinal changes in factors are in association with the occurrence of grade 3, 4, or 5 toxicities in patients with weekly paclitaxel, nabpaclitaxel, or ixabepilone combined with or without bevacizumab. (Exploratory) XVII. To explore the association between grade 2-4 neuropathy and longitudinal changes in the following functional status measures: a) OARS MFAQ (IADL); b) MOS Physical Functioning; c) Karnofsky Performance Status Rated Healthcare Professional; d) Timed "Up and Go"; e) OARS Physical Health Section.
OUTLINE: This is a multicenter study. Patients are stratified according to taxane as adjuvant therapy (yes or no), estrogen receptor (ER) or progesterone receptor (PgR) status (ER-positive or PgR-positive vs both ER-negative and PgR-negative), physician's decision to use bevacizumab (yes vs no). 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. Patients may also receive 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. Patients may also receive bevacizumab as in arm I.
ARM III: (weekly ixabepilone) Patients receive ixabepilone IV over 60 minutes on days 1, 8, and 15. Patients may also receive 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. Blood samples may be collected at baseline and periodically during study for correlative studies. Tumor tissue samples from diagnosis may be also collected.
After completion of study therapy, patients are followed every 6 months for 2 years and then annually for up to 3 years.
- 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:
- 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
- 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-hoururine 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
- 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
- No prior chemotherapy regimen for metastatic disease
- 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
- There are no restrictions on core biopsies, placement of a vascular access device, or other minor procedures prior to registration.
- 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
Trial Lead Organizations/Sponsors
National Cancer Institute
|Hope S. Rugo||Principal Investigator|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00785291
ClinicalTrials.gov processed this data on July 22, 2014
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