Phase II Trial of Neoadjuvant Chemotherapy [NCT] With Weekly Nanoparticle Albumin-bound Paclitaxel [Nab-paclitaxel; Abraxane®] in Combination With Carboplatin and Bevacizumab in Women With Clinical Stages I-III Breast Cancer
18 Years
N/A
Female
Breast Cancer
Trial Information
Phase II Trial of Neoadjuvant Chemotherapy [NCT] With Weekly Nanoparticle Albumin-bound Paclitaxel [Nab-paclitaxel; Abraxane®] in Combination With Carboplatin and Bevacizumab in Women With Clinical Stages I-III Breast Cancer
OBJECTIVES:
Primary
- To determine the complete pathological response (pCR) in the breast/axillary lymph
nodes in women with stage II or III breast cancer treated with neoadjuvant therapy
comprising paclitaxel albumin-stabilized nanoparticle formulation, carboplatin, and
bevacizumab followed by surgery and adjuvant bevacizumab.
- To determine the side effects of this regimen in these patients.
Secondary
- To evaluate dynamic contrast-enhanced magnetic resonance imaging in assessing pCR.
- To measure LZTS1 gene expression before and after neoadjuvant therapy to evaluate
whether LZTS1 gene expression correlates with pCR.
- To evaluate the feasibility and toxicity of adjuvant bevacizumab when administered for
6 months.
OUTLINE:
- Neoadjuvant therapy: Patients receive paclitaxel albumin-stabilized nanoparticle
formulation IV over 30 minutes and carboplatin 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
for 5 courses. After completion of course 5, patients receive paclitaxel
albumin-stabilized nanoparticle formulation IV over 30 minutes and carboplatin IV over
30 minutes on days 1, 8, and 15. Patients then proceed to surgery.
- Surgery: Approximately 4-5 weeks after completion of neoadjuvant therapy, patients
undergo definitive surgery (either lumpectomy or mastectomy). Patients with
node-positive disease or inflammatory breast cancer at baseline also undergo axillary
lymph node dissection. Patients then proceed to adjuvant therapy.
- Adjuvant therapy: Beginning approximately 6 weeks after surgery, patients receive
bevacizumab IV over 30-90 minutes once every 3 weeks for 6 months. Patients with
hormone receptor-positive disease also receive endocrine therapy. Patients may also
receive additional adjuvant chemotherapy or radiotherapy at the discretion of the
treating physician.
Patients undergo dynamic contrast-enhanced magnetic resonance imaging at baseline, after
course 2 of neoadjuvant therapy, and after completion of neoadjuvant therapy (prior to
definitive surgery) for assessment of tumor response. Tumor tissue is collected at baseline
and during surgery for correlative laboratory studies. LZST1 gene expression is assessed by
immunohistochemistry before and after neoadjuvant therapy.
Inclusion Criteria
Inclusion:
- Histologically confirmed breast cancer
- Clinically or radiographically measurable residual tumor after core biopsy
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Age ≥18 yrs
- Absolute neutrophil count ≥ 1,500/mm³
- Hemoglobin ≥ 9 g/dL
- Platelet count ≥ 100,000/ mm³
- Creatinine ≤ 1.5 times upper limit of normal (ULN)
- Urine protein:creatinine ratio < 1.0
- AST and ALT ≤ 2.5 times ULN
- Alkaline phosphatase ≤ 2.5 times ULN
- Bilirubin normal
- Women of childbearing potential must use effective contraception
- Left ventricular ejection fraction (LVEF) normal by echocardiogram or MUGA
Exclusion:
- No residual tumor after initial biopsy
- Peripheral neuropathy of grade 2 or higher
- HER-2 neu overexpression either by IHC 3+ or FISH+
- No history of any prior treatment of breast cancer.
- No history of unstable angina or myocardial infarction within the past 12 months
- Pregnant or nursing women
- Anticoagulation therapy within the last 6 months
- History of gastrointestinal bleeding
- Recent hemoptysis
- No known hepatitis B or HIV seropositivity
- No inadequately controlled hypertension, defined as systolic blood pressure (BP) >
150 mm Hg and/or diastolic BP > 100 mm Hg despite antihypertensive medications
- History of hypertensive crisis or hypertensive encephalopathy
- New York Heart Association class II-IV congestive heart failure
- History of stroke or transient ischemic attack at any time
- Significant vascular disease (e.g., aortic aneurysm or aortic dissection)
- No symptomatic peripheral vascular disease
- Evidence of bleeding diathesis or coagulopathy
- Significant traumatic injury within the past 28 days
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within the past 6 months
- Serious, non-healing wound, ulcer, or bone fracture
- Known hypersensitivity to any component of bevacizumab
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Pathologic complete response (pCR) and side effects of weekly nab-paclitaxel, carboplatin and bevacizumab.
Outcome Time Frame:
every 4 weeks
Safety Issue:
No
Principal Investigator
Ewa Mrozek, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Ohio State University
Authority:
United States: Food and Drug Administration
Study ID:
OSU-07074
NCT ID:
NCT00675259
Start Date:
July 2008
Completion Date:
Related Keywords:
- Breast Cancer
- stage II breast cancer
- stage IIIA breast cancer
- stage IIIB breast cancer
- stage IIIC breast cancer
- Breast Neoplasms
Name | Location |
|---|---|
| Ohio State University Medical Center | Columbus, Ohio 43210 |
