Concurrent Adjuvant Carboplatin and Accelerated Radiotherapy 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 the safety and effectiveness of a combination of chemotherapy and radiotherapy in breast cancer patients after breast surgery.

Detailed Description
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Preliminary experience in the neo-adjuvant setting of Locally Advanced Breast Cancer (LABC) has recently demonstrated that hormone receptors negative patients have approximately 50% chance to achieve a pathological response after concurrent chemo-radiation. In a multi-institutional collaboration of 105 patients it was found that triple negative (TN) tumor carriers achieved pathological response in 54% of the cases and that the response reflected on 5-year disease free survival and overall survival. Our group has speculated that these effects on the risk of distant recurrence could depend on the recovery of antitumor immunity among the patients achieving pathological response, after tumor cell death induced by concurrent chemo-radiation. The investigators are proposing a novel study that translates these findings to the adjuvant setting of TN tumors. TN breast cancer is a more aggressive form of the disease often coinciding with basal-like tumors. BRCA mutated-cancer is more frequently TN. The current protocol converges the experience NYU has developed in accelerated prone breast radiotherapy with encouraging finding from the use of concurrent chemoradiation in LABC. The investigators will study the feasibility of combining weekly carboplatin with concurrent 3-weeks prone breast radiotherapy in the adjuvant setting of 35 women with TN tumors, after segmental mastectomy and nodal assessment. Primary endpoint of the study is acute toxicity of the combined regimen, with a target of < 25% of grade II-III dermatitis.

Official Title
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Phase I-II Study of Concurrent Adjuvant Systemic Therapy and Accelerated Radiotherapy (Over 3 Weeks)

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Carboplatin
* Radiation: 3D-RT or IMRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age older than 18 Pre- or post-menopausal women with Stage I and II breast cancer, triple negative tumors Biopsy-proven invasive breast cancer, excised with negative margins of at least 1 mm Status post segmental mastectomy, after sentinel node biopsy and/or axillary node dissection (Tumors < 5 mm in size do not require nodal assessment) or after mastectomy No previous chemotherapy Patient needs to be able to understand and demonstrate willingness to sign a written informed consent document Exclusion Criteria: Previous radiation therapy to the ipsilateral breast Active connective tissue disorders, such as lupus or scleroderma Pregnant or lactating women

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: ChemoRT<br>Concurrent Carboplatin and Radiotherapy | Drug: Carboplatin<br>* IV, weekly for 6 weeks, AUC of 2.0<br>* Other names: Paraplatin;Radiation: 3D-RT or IMRT<br>* From week 2 to week 4 in the 6-week Carboplatin treatment: Whole Breast 3D-RT or IMRT at 2.7 Gy X 15 fractions (5 times/wk x 3 wks=40.50 Gy), then the second and third Friday, 3 Gy to the tumor bed only X 2 fractions, Total dose to tumor bed = 46.5 Gy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Developed Grade 2-3 Acute Radiation Dermatitis Within 60 Days Post-RT |  | 60 days post-RT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Experience Acute Toxicities at or More Than 6 Months After Completion of Radiation Treatment (RT) | Acute Toxicities include all Grade 1 toxicities | 6 months to 5 year post-RT | 
| Number of Patients Who Experience Grade 2 or Higher Late Toxicities at or More Than 6 Months After Completion of Radiation Treatment (RT) |  | 6 months to 5 years post-RT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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triple negative, breast cancer, adjuvant therapy, Carboplatin, chemotherapy, radiation therapy, chemo-radiotherapy, accelerated radiotherapy