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

Study Overview
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Brief Summary
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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
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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

Official Title
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Effect of Neoadjuvant Cisplatin Based Chemoradiation Therapy for Locally Advanced Triple Negative Breast Cancer: Clinical Outcome and Correlation to Biological Parameters

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Cisplatin
* Radiation: Radiation Therapy
* Procedure: Mastectomy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cisplatin + Radiation + Recommended Surgery<br>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 | Drug: Cisplatin<br> <br> * Other names: cisplatinum;Radiation: Radiation Therapy<br> <br> Procedure: Mastectomy<br>* (RECOMMENDED BUT NOT REQUIRED)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response | 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. | At the time of surgery (week 13) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Disease Progression | Time to disease progression: time from registration until objective tumor progression; does not include deaths | Until study was terminated (23.5 months) | 
| Overall Survival Rate (OS) | OS = Time from registration until death from any cause | Until study was terminated (23.5 months) | 
| Number of Participants With Surgical Complications |  | 30 days post surgery (week 17-18) | 
| Number of Participants With Medical Toxicities | 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. | 30 days post surgery (week 17-18) | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Locally Advanced, Neoadjuvant