A Single Arm Phase 2 Study of Peri-Operative Immune Checkpoint Inhibition and Cryoablation in Women With Hormone Receptor-Negative, HER2-Negative Early Stage/Resectable Breast Cancer.
The purpose of this study is to determine the impact of pre-operative cryoablation, and immune checkpoint inhibition (ICI) on on 3-year Event Free Survival (EFS), in women with residual hormone receptor negative, HER2-negative (triple negative) resectable breast cancer after taxane-based neoadjuvant chemotherapy.
• Women age 18 years or older
• Confirmed histologic diagnosis of invasive carcinoma of the breast
• Pathology confirmation of invasive carcinoma (reported or requested and pending)
• ER, PR and HER2 negative on outside or Cedars Sinai biopsy report, where ER and PR negative are defined as staining present in ≤10% of invasive cancer cells by IHC, and HER2-negative is defined as IHC 0-1+ or FISH \<2.0. If ER, PR and HER2 status are not reported the results must be requested and pending.
• Operable tumor measuring ≥1.0 cm in maximal diameter
• Any nodal status allowed, including negative nodal status.
• Multifocal and multicentric disease is permitted if all foci have been biopsied and also meet the criteria for TNBC.
• Synchronous bilateral invasive breast cancer is permitted if all foci have been biopsied and also meet the criteria for TNBC.
• No indication of distant metastases
⁃ Total mastectomy or lumpectomy planned
⁃ Tumor amenable to cryoablation as determined by a study radiologist
⁃ ECOG performance status score of 0 or 1.
⁃ Screening laboratory values must meet the following criteria:
∙ White blood cells (WBCs) ≥ 2000/μL
‣ Absolute neutrophil count (ANC) ≥ 1500/μL
‣ Platelets ≥ 100 x 103/μL ii. Hemoglobin ≥ 9.0 g/dL iii. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below): Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL
‣ AST/ALT ≤ 3 x upper limit of normal (ULN)
‣ Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert's syndrome, who must have total bilirubin \< 3.0 mg/dL)
⁃ Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab and, ipilimumab, and pembrolizumab to undergo five half-lives) after the last dose of investigational drug.
⁃ Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG). Women must not be breastfeeding
⁃ Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.