Genomically Guided Radiation Therapy in the Management of Triple Negative Breast Cancer

Study Overview
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Brief Summary
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The purpose of the study is to determine the feasibility of genomically guided radiation therapy (RT) in people with triple negative (HER2 negative, hormone receptor negative) breast cancer undergoing breast conservation therapy.

Official Title
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Phase II Study of Genomically Guided Radiation Dose Personalization in the Management of Triple Negative Breast Cancer

Conditions
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Triple Negative Breast Cancer

Intervention / Treatment
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* Radiation: Genomically Guided Radiation Therapy
* Radiation: Genomically Guided Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants should have undergone breast conservation therapy with a lumpectomy and axillary evaluation to consist of a sentinel node biopsy or axillary dissection Confirmation of Triple Negative (TN) breast cancer by tissue biopsy Adequate tissue to calculate RSI To fulfill the requirement of HER2- disease, a breast cancer must not demonstrate, at initial diagnosis or upon subsequent biopsy, overexpression of HER2 by either IHC or in-situ hybridization as defined by the ASCO / CAP Guidelines To fulfill the requirement of hormone receptor (HR)- disease, a breast cancer must express (<5%), by immunohistochemistry (IHC), the hormone receptors (estrogen receptor [ER] and progesterone receptor [PR]) as defined in the American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP) Guidelines Life expectancy >16 weeks KPS ≥ 70 Age ≥ 18 years Participants with surgery within 14 days should have recovered from all effects of the surgery and be cleared by their surgeon There is no limit on prior systemic therapies Women of childbearing potential and sexually active males must commit to the use of effective contraception while on study Ability to sign an informed consent form, which can be signed by a family member or health care proxy. Informed consent must be given before study enrollment Exclusion Criteria: Major surgery or significant traumatic injury that has not been recovered from 14 days before study initiation Women who are pregnant or breastfeeding Positive surgical margins History of allergy or hypersensitivity to any of the study drugs or study drug components Metastatic breast cancer

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radiosensitivity Index optimized<br>Participants will be assigned to optimized arm based on their RSI score. Participants will receive whole breast radiation therapy with or without regional lymph node irradiation as appropriate with or without a boost to the lumpectomy cavity. | Radiation: Genomically Guided Radiation Therapy<br>* Participants will receive treatment 5 days per week, in once daily fractions. The total dose will be 50 Gy in 25 fractions or 42.56 Gy in 16 fractions with or without a boost of 10 Gy in 5 fractions to the cavity.<br>|
| Active Comparator: Radiosensitivity Index not optimized<br>Participants will receive standard of care whole breast radiation therapy with or without regional lymph node irradiation as appropriate with a boost to the lumpectomy cavity. | Radiation: Genomically Guided Radiation Therapy<br>* Participants will receive treatment 5 days per week, in once daily fractions. The total dose will be 50 Gy in 25 fractions or 42.56 Gy in 16 fractions with a boost of 10 Gy in 5 fractions to the cavity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Control | Local control will be defined as lack of progression in the ipsilateral breast as documented by response assessment imaging | At 3 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS will be measured from the date of study initiation to the date of death due to any cause. | Up to 5 Years | 
| Progression Free Survival (PFS) | PFS is measured from the date of first treatment to the date of first observation of PD or death due to any cause. | Up to 5 years | 
| Distant Control | Distant control will be defined by lack of progression outside the irradiated treatment field | Up to 5 Years | 
| Quality of Life following Genomically Guided Dose Personalization | Quality of life (QOL) will be assessed through the completion of the Functional Assessment of Cancer Therapy for Breast Cancer questionnaire (FACT-B). This quality of life questionnaire contains questions from the FACT-General (G) questionnaire in the domains of physical, social/family, emotional, and functional well-being as well as additional questions pertaining to patients with breast cancer. The questionnaire will be completed at screening, during protocol therapy and at follow-up visits | Up to 5 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Genomically Guided Radiation