Preoperative Use of Radiation Boost to Enhance Effectiveness of Immune Checkpoint Blockade Therapy in Operable Breast Cancer
The primary objective is to determine the feasibility of combining pembrolizumab with a single fraction radiation boost in patients with early/ operable breast cancer. The secondary objectives are to assess clinical response on pre- and post-treatment clinical, imaging, and histology exams, and to assess immune response on pre and post treatment blood and tissue samples by tracking change in Ki67 + CD8 T cells in peripheral blood and in extent of tumor infiltrating lymphocytes. A clinically significant partial response is defined as \>30% tumor shrinkage post-clinical trial intervention.
⁃ Men and women age ≥ 18 years old (unless otherwise specified) Willing and able to provide written informed consent/assent ECOG Performance Status 0 - 1
⁃ Patients with:
⁃ Newly diagnosed breast cancer with tumor size \< 5 cm who are not eligible for I-SPY2 (to prevent recruitment competition), or not recommended to undergo standard of care neoadjuvant chemotherapy with at least one of the following features:
• Triple negative breast cancer (TNBC) defined using the ASCO CAP guidelines with the following modification supported by a recent publication as ER ≤ 10%, PR ≤ 10%, HER2- determined by immunohistochemistry and/or fluorescence in situ hybridization analyses and with tumor size ≤ 2.5 cm;
• HR+ HER2- breast cancer regardless of nodal status and age of diagnosis ≥ 50
• HR+ HER2- breast cancer and age of diagnosis \<50 with tumor size ≤ 2.5 cm and clinically node (+)
• HR+ or HR- and HER2+ breast cancer with tumor size ≤ 2.5 cm
• Ductal carcinoma in situ (DCIS) with microinvasion
⁃ OR
• Locally recurrent breast cancer of any receptor subtype with no prior radiation, not recommended to receive neoadjuvant chemotherapy and expecting surgical excision as part of treatment.
⁃ A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
⁃ Not a woman of childbearing potential (WOCBP) as defined in Appendix 2 of the study protocol OR
⁃ A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 during the treatment period and for at least 120 days for study treatments with risk of genotoxicity after the last dose of study treatment.
∙ Female participants of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Medically accepted methods of birth control include a diaphragm, cervical cap, latex condoms, surgical sterility, intrauterine devices (IUDs), hormonal implants, injectable contraceptives, or birth control pills. Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
‣ Ability to tolerate radiation therapy (e.g., lie flat and hold position)
‣ Demonstrate adequate hematologic, renal, hepatic, thyroid, and bone marrow function
• Men and women age ≥ 18 years old (unless otherwise specified)
• Willing and able to provide written informed consent/assent
• ECOG Performance Status 0 - 1
• Patients with:
‣ Newly diagnosed breast cancer with tumor size \< 5 cm who are not eligible for I-SPY2 (to prevent recruitment competition), or not recommended to undergo standard of care neoadjuvant chemotherapy with at least one of the following features:
• Triple negative breast cancer (TNBC) defined using the ASCO CAP guidelines with the following modification supported by a recent publication as ER ≤ 10%, PR ≤ 10%, HER2- determined by immunohistochemistry and/or fluorescence in situ hybridization analyses and with tumor size ≤ 2.5 cm;
∙ HR+ HER2- breast cancer regardless of nodal status and age of diagnosis ≥ 50
∙ HR+ HER2- breast cancer and age of diagnosis \<50 with tumor size ≤ 2.5 cm and clinically node (+)
∙ HR+ or HR- and HER2+ breast cancer with tumor size ≤ 2.5 cm
∙ Ductal carcinoma in situ (DCIS) with microinvasion
⁃ OR
• Locally recurrent breast cancer of any receptor subtype with no prior radiation, not recommended to receive neoadjuvant chemotherapy and expecting surgical excision as part of treatment.
• • A female participant is eligible to participate if she is not pregnant (see Appendix 2), not breastfeeding, and at least one of the following conditions applies:
‣ Not a woman of childbearing potential (WOCBP) as defined in Appendix 2. OR
‣ A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 during the treatment period and for at least 120 days for study treatments with risk of genotoxicity after the last dose of study treatment.
∙ • Female participants of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Medically accepted methods of birth control include a diaphragm, cervical cap, latex condoms, surgical sterility, intrauterine devices (IUDs), hormonal implants, injectable contraceptives, or birth control pills. Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
• Ability to tolerate radiation therapy (e.g., lie flat and hold position)
• Demonstrate adequate hematologic, renal, hepatic, thyroid, and bone marrow function