Peri-Operative Ipilimumab+Nivolumab and Cryoablation in Women With Triple-negative Breast Cancer

• Status: Recruiting
• Trial end date: 2024-06-01
• Target enrollment: 0
• Participant gender: Female

Summary

The purpose of this study is to determine the impact of pre-operative cryoablation, ipilimumab and nivolumab 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cedars-Sinai Medical Center; Monica Mita
• Collaborator: Memorial Sloan Kettering Cancer Center
• Treatments: Antibodies, Monoclonal; Ipilimumab; Nivolumab

Criteria

Inclusion Criteria:

• 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

• Multifocal and multicentric disease is permitted.

• Synchronous bilateral invasive breast cancer is permitted

• 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)

• No history of known HIV

• No history of known active hepatitis B or hepatitis C

• 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 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.

• Prior checkpoint blockade administration is permitted with a washout period of 3 weeks

• "Women of childbearing potential" is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes.

Women of childbearing potential (WOCBP) receiving nivolumab and ipilimumab will be instructed to adhere to contraception for a period of 23 weeks after the last dose of investigational product. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product. These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days.

Exclusion Criteria:

• Medical history and concurrent diseases

• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Note: Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.

• Any underlying medical or psychiatric condition, which in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of AEs, such as a condition associated with frequent or poorly controlled diarrhea.

• Prohibited Treatments and/or Therapies

• Chronic use of immunosuppressants and/or systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses). Brief periods of steroid use, for example for the management of chemotherapy-associated toxicities, are allowed. The use of corticosteroids on study is allowed for the treatment of immune related adverse events (irAEs) and other medical conditions including adrenal insufficiency.

• Any non-oncology live vaccine therapy used for prevention of infectious diseases within 3 weeks prior to first dose of ipilimumab.

• Prior investigational agents within 3 weeks prior to ipilimumab/nivolumab