Effect of Chemotherapy and Radiation Prior to Surgery for Triple Negative Breast Cancer

Phase 2

Terminated

Interventions: Drug: Cisplatin
Radiation: Radiation Therapy
Procedure: Mastectomy

Brief Summary: The purpose of this study is to determine whether Cisplatin when given with radiation therapy prior to surgery is effective in improving response to treatment in breast cancer patients. Tumor, blood and bone marrow samples will be collected in this study and will also help researchers determine if cisplatin is able to change tumor DNA so it cannot multiply itself and create more tumor cells, and cause the tumor cells to die.

Detailed Description: After Diagnosis: Clinical Stage IIB, III Breast Cancer, Triple Negative

Week 0: Port-A-Cath placement Tumor biopsy (Core and FNA) Blood collection Bone marrow aspiration Sentinel Lymph node biopsy, if axillary US negative

Week 1: Chemo \& Radiation Day 1: Radiation Therapy, Cisplatin 75mg/m\^2 (cycle 1) Days 2-5: Radiation Therapy

Week 2: Radiation Day 1-5: Radiation Therapy

Week 3: Radiation Days 1-5: Radiation Therapy

Week 4: Chemo \& Radiation Day 1: Radiation Therapy, Cisplatin 75mg/m\^2 (cycle 2) Days 2-5: Radiation Therapy

Week 5: Radiation Days 1-5: Radiation Therapy

Week 6: Radiation Days 1-5: Radiation Therapy

Week 7: Chemo Day 1: Cisplatin 75mg/m\^2 (cycle 3)

Week 10: Chemo Day 1:Cisplatin 75mg/m\^2 (cycle 4)

Week 13: Surgery Mastectomy with/without axillary lymph node dissection Tumor biopsy (Core and FNA) Blood collection Bone marrow aspiration

Week 15 - 21: Recommended (physician discretion) Adjuvant Chemo Dose dense Doxorubicin: 60mg/m\^2 \& Cyclophosphamide: 600mg/m\^2, every 2 weeks for 4 cycles

Week 21 - 29: Recommended (physician discretion) Adjuvant Chemo Paclitaxel: 175mg/m\^2 every 2 weeks for 4 cycles

Week 52 IVAD Removal, Bone marrow aspiration

Follow-Up (up to 5 years) Q 3 months for year 1 Q 6 months for year 2-3 Q 1 year for years 4-5

Recruitment & Eligibility

Inclusion Criteria

Patients must be >= 18 years of age
Patients must be newly diagnosed with primary invasive ductal breast adenocarcinoma.
Tumor classified as clinically stage T2, T3 or T4 with any N (NX, N1, N2, or N3).
Tumor does not express the following biomarkers: estrogen receptor, progesterone receptor, Her2/neu
Adequate organ function defined as:
- Serum Creatinine <= 1.5 x upper limit of institutional normal.
- ALT, AST, ALK Phos <= 1.5 x upper limit of institutional normal.
- Bilirubin <= 1.5 x upper limit of institutional normal.
- Normal left ventricular function (LVEF > 50%) by MUGA or ECHO.

Exclusion Criteria

No evidence of distant metastasis present by CT, Bone scan, or physical exam. If the bone scan or CT scans demonstrate indeterminate lesions, the nature of these lesions should be further clarified by additional testing such as PET or MRI.
No prior malignancies with the exception of curatively treated basal or squamous carcinoma of the skin or history of previous malignancies, treated with at least greater than 5 years disease free survival.
Women of child bearing potential may not be currently pregnant or breastfeeding at time of registration and must agree to use adequate contraception.
Karnofsky Performance Status of <= 70.
Patients with known history neural deficiencies (e.g. peripheral neuropathy).
Patients with a known hearing impairment (hearing loss or severe tinnitus).
Male patients

Arm && Interventions

Group	Intervention	Description
Cisplatin + Radiation + Recommended Surgery	Radiation Therapy	Cisplatin 75 mg/m\^2 IV Day 1 Week 1, Day 1 Week 2, Day 1 Week 7, Day 1 Week 10 Radiation = Total dose to breast or chest wall will be 50-60 Gy in 1.8-2.0 Gy daily fractions. Internal mammary nodes, supraclavicular fossa nodes and axillary nodal basins will receive 45-50 Gy over 5-6 weeks. Surgery (recommended) mastectomy with/without axillary lymph node dissection
Cisplatin + Radiation + Recommended Surgery	Mastectomy	Cisplatin 75 mg/m\^2 IV Day 1 Week 1, Day 1 Week 2, Day 1 Week 7, Day 1 Week 10 Radiation = Total dose to breast or chest wall will be 50-60 Gy in 1.8-2.0 Gy daily fractions. Internal mammary nodes, supraclavicular fossa nodes and axillary nodal basins will receive 45-50 Gy over 5-6 weeks. Surgery (recommended) mastectomy with/without axillary lymph node dissection
Cisplatin + Radiation + Recommended Surgery	Cisplatin	Cisplatin 75 mg/m\^2 IV Day 1 Week 1, Day 1 Week 2, Day 1 Week 7, Day 1 Week 10 Radiation = Total dose to breast or chest wall will be 50-60 Gy in 1.8-2.0 Gy daily fractions. Internal mammary nodes, supraclavicular fossa nodes and axillary nodal basins will receive 45-50 Gy over 5-6 weeks. Surgery (recommended) mastectomy with/without axillary lymph node dissection

Primary Outcome Measures

Name	Time	Method
Overall Response	At the time of surgery (week 13)	* Complete response: disappearance of all target lesions, non-target lesions, and normalization of tumor marker level * Partial response: at least a 30% decrease in the sum of the longest diameter (LD) of the target lesions taking as reference the baseline sum LD * Stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD since the treatment started, * Progressive disease: at least a 20% increase in the sum of the LD of the target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions, appearance of one more new lesions, or unequivocal progression of existing non-target lesions.

Secondary Outcome Measures

Name	Time	Method
Overall Survival Rate (OS)	Until study was terminated (23.5 months)	OS = Time from registration until death from any cause
Number of Participants With Surgical Complications	30 days post surgery (week 17-18)
Number of Participants With Medical Toxicities	30 days post surgery (week 17-18)	The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for all toxicity reporting. All detailed information regarding serious and other adverse events are listed in the Adverse Event module of these results.
Time to Disease Progression	Until study was terminated (23.5 months)	Time to disease progression: time from registration until objective tumor progression; does not include deaths
Effect of Neoadjuvant Chemoradiation Therapy in Disseminated Cancer Cells in the Bone Marrow and Correlation to Tumor Response	5 years
Develop Animal Models of Triple Negative Breast Cancers	5 years
Provide Samples for the Development of the FNA Assay	At time of IVAD placement and at time of surgery