Homologous Recombination Repair Status as a Biomarker of Response in Locally Recurrent/Metastatic Triple Negative Breast Cancer Patients Treated With Concurrent Cisplatin and Radiation Therapy

Study Overview
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Brief Summary
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The study is being done to find out if the results of a pre-treatment biopsy can predict response to cisplatin and radiation treatment for patients with metastatic or recurrent triple negative breast cancer.

Official Title
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A Phase II Trial of Homologous Recombination Repair Status as a Biomarker of Response in Locally Recurrent/Metastatic Triple Negative Breast Cancer Patients Treated With Concurrent Cisplatin and Radiation Therapy

Conditions
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Locally Recurrent/Metastatic Triple Negative Breast Cancer

Intervention / Treatment
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* Radiation: external beam radiation therapy
* Drug: cisplatin
* Procedure: Biopsy of Target Tumor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically-confirmed invasive triple negative breast cancer (ER <1%, PR <1%, her-2-neu 0-1+ by IHC or FISH-negative) or as determined by MD discretion Radiation to the recurrent or metastatic site is clinically indicated and would be considered standard care for palliation or for locoregional control Age ≥18 years Tumor to be irradiated is measurable by RECIST 1.1 or PRC Willingness to undergo tumor biopsy prior to initiation of treatment Life expectancy greater than 6 months ECOG performance status 0-2 Any prior chemotherapy is allowed including prior treatment with platinum-containing chemotherapy Prior treatment with FDA-approved or investigational biologics or novel molecularly target therapies, including oral or IV formulations, are permitted. Patients must be off prior targeted therapy for at least 14 days prior to study biopsy. Use of an effective means of contraception in women of child-bearing potential Ability to comprehend and sign informed consent Adequate organ and marrow function within 14 days prior to study entry, defined as: Absolute neutrophil count (ANC)>1000/mm3 Hemoglobin >9 gm/dl Platelets >100,000/mm3 Serum creatinine <1.5 mg/dl OR creatinine clearance of ≥ 50 cc/min SGOT/SGPT<2.5X institutional ULN (<5X ULN if known liver metastases) Exclusion Criteria: Unmeasurable target tumor site by RECIST 1.1 or PRC (ex: lesions <2 cm on CT or MR scan, leptomeningeal disease, ascites, pleural/pericardial effusion, lymphangitis, non-FDG-avid skin lesions) Brain metastases requiring focal or whole brain radiation will be excluded, as these lesions cannot be biopsied and can have life expectancies <6 months. Inability to obtain a biopsy of the tumor as deemed by the study Interventional Radiologist Prior chemotherapy completed <7 days prior to planned study entry Prior RT is allowed and must have been completed more than 7 days before planned study entry. Note: For re-irradiation cases, standard departmental guidelines should be followed so as to not exceed normal tissue Life expectancy less than 6 months Intercurrent illness or other major medical condition or comorbid condition that might affect study participation (uncontrolled renal, pulmonary or hepatic dysfunction or infection) Renal dysfunction for which cisplatin dose would be considered unsafe. Women on study must be neither pregnant nor nursing nor expected to become pregnant during therapy. For premenopausal women, negative pregnancy test within 14 days of RT is required. Concurrent active malignancy other than non-melanomatous skin cancer or carcinoma in-situ of the cervix, unless treatment for the previous cancer was completed >2 years prior to study entry and patient has remained disease-free.

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: Concurrent Cisplatin & Radiation Therapy<br> | Radiation: external beam radiation therapy<br>* Radiation therapy to the target tumor will be delivered with external beam radiation therapy. In metastatic cases where the intent is palliative, the dose of radiation will be 3750 cGy delivered in 15 daily fractions, 4-5 days a week. In locoregionally recurrent cases where the intent is to enhance locoregional control, the dose of radiation will be 5000 cGy delivered in 25 fractions, 4-5 days a week plus an optional 10-14 Gy boost to areas of gross tumor.<br>Drug: cisplatin<br>* Cisplatin treatment should be initiated following study registration. The dose of cisplatin is established as 25 mg/m^2 ivpb once a week (+ 3 days) for 1-2 weeks prior to radiation. The length of one cycle of Cisplatin is 21 days.<br>Procedure: Biopsy of Target Tumor<br>* Biopsy of the tumor to be irradiated will be performed. Fresh tissue specimens will be sent to the laboratory for performance of the MSK-HRR Assay.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response (RECIST 1.1 vs. PET Response Criteria (PRC) as measurement tools for treatment response) | Compare the efficacy of RECIST 1.1 vs. PET Response Criteria (PRC) as measurement tools for treatment response. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treated with Concurrent Cisplatin, Treated with Radiation Therapy, Homologous Recombination Repair Status, Biomarker of Response, 15-032, Patients