Carboplatin and Nab-Paclitaxel With or Without Vorinostat in Treating Women With Newly Diagnosed Operable Breast Cancer
Breast Cancer
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, ductal breast carcinoma, lobular breast carcinoma
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed infiltrating ductal breast cancer by core needle biopsy
- Mixed ductal and lobular disease allowed
- Infiltrating lobular cancer allowed in the run-in portion only
Unresected, clinically measurable disease, meeting 1 of the following clinical staging criteria:
- T2, T3, or T4 lesion, any N, M0
- T1c, N1-3,M0
- Patients with skin metastases to the ipsilateral breast for whom chemotherapy is planned prior to definitive surgery are eligible for the primary study portion
- HER2-negative disease
Hormone receptor status* meeting 1 of the following criteria:
- Estrogen receptor (ER)-negative and progesterone receptor (PR)-negative
- ER-positive (grade II or III) and PR-positive or PR-negative NOTE: *Any ER or PR status for the run-in portion
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- Menopausal status not specified
- ANC ≥ 1,500/mm³
- Platelet count ≥ 150,000/mm³
- Hemoglobin ≥ 9 g/dL
- Creatinine ≤ 1.5 times the upper limit of normal (ULN)
- Creatinine clearance ≥ 50 mL/min
- Total bilirubin normal
- AST(SGOT) and ALT(SGPT) ≤ 2.5 times (ULN)
- alkaline phosphatase ≤ 2.5 times ULN
- PT such that INR ≤ 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and PTT ≤ ULN
- Adequate cardiac function defined as no evidence of PR prolongation or AV block on baseline electrocardiogram (ECG)
- Willing to use effective, non-hormonal contraception while on treatment and for at least 3 months thereafter
- Not pregnant or nursing
- No pre-existing peripheral neuropathy ≥ grade 2
- No history of severe hypersensitivity reaction to any drug formulated with polysorbate 80 or to E. coli-derived products
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat
- No medical condition which, in the opinion of the investigator, puts the patient at risk of potentially serious complications while on this therapy
PRIOR CONCURRENT THERAPY:
- At least 4 weeks since prior valproic acid or other histone deacetylase inhibitor
No prior chemotherapy, radiotherapy, or endocrine therapy for this cancer
- Prior tamoxifen or raloxifene or another agent for prevention of breast cancer allowed as long as the patient has discontinued the treatment ≥ 1 month prior to baseline study biopsy
- No systemic treatment for prior cancer within the past 5 years (primary study portion)
- No prior or ongoing systemic treatment for this cancer (primary study portion)
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent histone deacetylase inhibitor
- No other concurrent chemotherapy, antiestrogen therapy, radiotherapy, or other investigational systemic therapy
- No other concurrent biologic therapy
- No other concurrent investigational drugs
Sites / Locations
- University of Alabama Comprehensive Cancer Center
- Indiana University Purdue University of Indianapolis
- Anne Arundel Health System
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Mayo Clinic Cancer Center
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Arm I
Arm II
Patients receive carboplatin IV and paclitaxel albumin-stabilized nanoparticle formulation IV on day 1 and an oral placebo on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.