A Pilot Study of Pre-Operative, Single-Dose Ipilimumab and/or Cryoablation in Early Stage/Resectable Breast Cancer
- Women age 18 years or older
- Confirmed histologic diagnosis of invasive adenocarcinoma of the breast, including
MSKCC pathology confirmation
- ER, PR and HER2 testing in progress(i.e. on outside or MSKCC biopsy report)
- HER2-positive pathology is permitted
- Operable tumor measuring ≥1.5 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 planned
- Tumor amenable to cryoablation as determined by 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
- Hemoglobin ≥ 11.0 g/dL
- Serum creatinine ≤ 2 mg/dL (or glomerular filtration rate ≥ 40 ml/min)
- AST ≤ 2.5 x upper limit of normal (ULN)
- ALT ≤ 2.5 x ULN
- Bilirubin within normal limits (except subjects with Gilbert's syndrome, who must
have total bilirubin < 3.0 mg/dL)
- Negative HIV screening test
- Negative screening tests for Hepatitis B and Hepatitis C.
- Patients with positive results that do not indicate true active or chronic infection
may enroll after discussion and consensus agreement by the treating physician and
- Women of childbearing potential (WOCBP) must be using an acceptable method of
contraception to avoid pregnancy throughout the study and for at least 3 months after
the last dose of ipilimumab in such a manner that the risk of pregnancy is minimized.
See below for the definition of WOCBP.
- WOCBP must have a negative serum pregnancy test within 14 days of the first study
- Women must not be breastfeeding.
- Willing to adhere to the study visit schedule and the prohibitions and restrictions
specified in this protocol.
- Definition of WOCBP
- Women of childbearing potential include any female who has experienced menarche and
who has not undergone successful surgical sterilization (hysterectomy, bilateral
tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Post menopause
is defined as:
- Amenorrhea ≥ 12 consecutive months without another cause and a documented serum
follicle stimulating hormone (FSH) level >35 mIU/mL
- Women with irregular menstrual periods and a documented FSH level > 35 mIU/mL
- Women on hormone replacement therapy (HRT) Women who are using oral contraceptives,
other hormonal contraceptives (vaginal products, skin patches, or implanted or
injectable products), or mechanical products such as an intrauterine device or
barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are
practicing abstinence or where their partner is sterile (e.g., vasectomy) should be
considered to be of childbearing potential.
- Inflammatory breast cancer
- Medical history and concurrent diseases
- Autoimmune disease: subjects with a documented history of inflammatory bowel disease,
including ulcerative colitis and Crohn's disease are excluded from this study as are
subjects with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic
progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune
vasculitis [e.g., Wegener's Granulomatosis]). Subjects with motor neuropathy
considered of autoimmune origin (e.g., Guillain-Barre Syndrome) are excluded from
- 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
- Prohibited Treatments and/or Therapies
a) Chronic use of immunosuppressants and/or systemic corticosteroids (used in the
management of cancer or non-cancer-related illnesses). However, use of
corticosteroids is allowed for the treatment of immune related Adverse Events
(irAEs), or adrenal insufficiency.
- Any non-oncology vaccine therapy used for prevention of infectious diseases within 4
weeks prior to first dose of ipilimumab.
- Prior treatment with a CD137 agonist, ipilimumab or other CTLA4 inhibitor;
- Prior investigational agents within 4 weeks prior to first dose of ipilimumab;
- Prior therapy with any anti-cancer agents including chemotherapy, adjuvant
chemotherapy, immunosuppressive agents, surgery or radiotherapy within 4 weeks prior
to first dose of ipilimumab.