A Study of Pre-Operative Treatment With Cryoablation and Immune Therapy in Early Stage Breast Cancer

A Pilot Study of Pre-Operative, Single-Dose Ipilimumab, Nivolumab and Cryoablation in Early Stage/Resectable Breast Cancer

This study is being done to evaluate the safety of combining two strategies called "cryoablation" and "immune therapy" in women with curable early stage breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Ipilimumab; Drug: Nivolumab; Procedure: Cryoablation

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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
  • The tumor should be more than 5 mm from the skin
• No indication of distant metastases
• Breast surgery 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 10^3/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 principal investigator.
• 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 prior to the first dose of ipilimumab/nivolumab
• Women must not be breastfeeding
• Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.

Exclusion Criteria:

• Inflammatory breast cancer

• Medical history and concurrent diseases

  • Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.

• Prohibited Treatments and/or Therapies

  • 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 2 weeks prior to first dose of ipilimumab;
  • Prior therapy with any anti-cancer agents including chemotherapy, adjuvant chemotherapy, immunosuppressive agents, surgery or radiotherapy within 2 weeks prior to first dose of ipilimumab.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cryoablation and Immune Therapy; Patients will undergo breast biopsy with cryoablation 7-10 days prior to the planned surgery, and ipilimumab with nivolumab administration 1-5 days before cryoablation. All patients will undergo surgery at the pre-determined day defined at the initial surgical consultation. Women will receive ipilimumab and nivolumab 1-5 days prior to US or MRI-guided core biopsy and cryoablation date. Intravenous ipilimumab will be administered as a single 1 mg/kg dose to be infused intravenously over 90 minutes. Intravenous nivolumab will be administered as a single 3 mg/kg dose to be infused intravenously over 60 minutes.

Drug: Ipilimumab; Drug: Nivolumab; Procedure: Cryoablation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Evaluated for Adverse Events	Safety will be evaluated for all treated subjects using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v4.0 (CTCAE).	12 weeks after ipilimumab/nivolumab administration.

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Elizabeth Comen, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): June 7, 2024
• Study Completion (Actual): June 7, 2024

Study Registration Dates

• First Submitted: July 12, 2016
• First Submitted That Met QC Criteria: July 13, 2016
• First Posted (Estimated): July 14, 2016

Study Record Updates

• Last Update Posted (Actual): October 23, 2024
• Last Update Submitted That Met QC Criteria: October 2, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Nivolumab; Ipilimumab; Resectable; Cryoablation; Early stage; 16-495
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Nivolumab; Ipilimumab
• Other Study ID Numbers: 16-495