Pre-Operative, Single-Dose Ipilimumab and/or Cryoablation in Early Stage/Resectable Breast Cancer

NCT01502592 | Completed Phase 1

• 1 other identifier: 11-202
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done to evaluate the safety of two strategies called "cryoablation" and "immune therapy" in women with curable early stage breast cancer. "Cryoablation" is a procedure performed by an expert doctor called a radiologist. The radiologist uses (magnetic resonance imaging (MRI) to insert a needle directly into a cancer. Very cold temperatures are then applied through the needle to kill the cancer cells. Some of the killed cancer cells will be broken into pieces that can be recognized by a person's immune system. The "immune therapy" in this study is a drug called ipilimumab. Normally the immune system makes "T cells" that can kill cancer cells when turned on. The cancer-killing T cell activity is controlled by a molecule called CTLA4. Ipilimumab works by turning off CTLA4. Turning off CTLA4 allows the cancer-fighting T cells to remain active Ipilimumab is an antibody drug has been made in a laboratory for patient use and was recently approved by the United States Food and Drug Administration (FDA) for the treatment of patients with a type of skin cancer called melanoma. An antibody is a normal protein that the immune system uses to find and kill germs like bacteria and viruses. This study is being done because the researchers believe that when cryoablation is combined with immune therapy, a person's immune system can be trained to recognize that person's cancer. This may prevent that cancer from coming back in the future. In other words, it is hoped that by adding cryoablation with ipilimumab before the mastectomy, the body will remain cancer free long after the mastectomy is performed. The first step in determining whether cryoablation and immune therapy can be used to cure breast cancer is to evaluate the safety of each strategy alone and then in combination in a small group of patients.

Conditions

Breast Cancer; Invasive Adenocarcinoma of the Breast

Keywords

MDX-010 (Ipilimumab); Cryoablation; Total mastectomy planned; 11-202

Outcome Measures

Primary Outcomes (2)

• safety

  of pre-operative ipilimumab administration and intratumoral cryoablation administered either alone or in combination in patients with early stage breast cancer. Safety will be evaluated for all treated subjects using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v4.0 (CTCAE).

  1 year

• tolerability

  If 5 of the 6 patients in study arm A and 5 of the 6 patients in study arm B are without an AE necessitating delay in surgery, we will enroll 6 additional patients into study arm C. If 5 or 6 of these 6 patients in study arm C are without an AE necessitating delay in surgery, the regimen will be considered safe/tolerable for further study. Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v4.0 (CTCAE).

  1 year

Secondary Outcomes (1)

• Efficacy

  1 year

Study Arms (3)

Cryoablation alone

EXPERIMENTAL

This is a pilot study evaluating the safety and tolerability of pre-operative, single-dose ipilimumab and/or cryoablation in patients with early stage/resectable breast cancer.

Procedure: Cryoablation

Ipilimumab alone

EXPERIMENTAL

This is a pilot study evaluating the safety and tolerability of pre-operative, single-dose ipilimumab and/or cryoablation in patients with early stage/resectable breast cancer.

Biological: Ipilimumab

Ipilimumab & Cryoablation

EXPERIMENTAL

This is a pilot study evaluating the safety and tolerability of pre-operative, single-dose ipilimumab and/or cryoablation in patients with early stage/resectable breast cancer.

Procedure: Cryoablation; Biological: Ipilimumab

Interventions

Cryoablation PROCEDURE

OncCore Biopsy (+ Cryo) Date\* * Pre- and post- cryo MRI * Core biopsy x ≥3 * Cryoablation Optional pre-surgery MRI day prior or day of Mastectomy Date\* Safety assessment 30 (+/-10) days after surgery research bloods 30 (+/-10) days after surgery.\*

Cryoablation alone; Ipilimumab & Cryoablation

Ipilimumab BIOLOGICAL

Ipilimumab Appt. with Med Onc Ipilimumab administered Core Biopsy Date\* * MRI * Core biopsy x ≥3 Optional pre-surgery MRI biopsy prior or day of Mastectomy Date\* Safety assessment 2-3 weeks post-mastectomy (co-ordinated with off-study surgery follow-up appt if feasible) and then every 2-3 weeks thereafter until at least 12 weeks post ipilimumab date. # Research bloods 30 (+/-10) days after surgery.

Ipilimumab & Cryoablation; Ipilimumab alone

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 this study.
• 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
• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan-Kettering Cancer Center

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cryosurgery; Ipilimumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Ablation Techniques; Surgical Procedures, Operative; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Heather McArthur, MD, MPH

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2011
• First Posted: December 30, 2011
• Study Start: December 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: January 5, 2016

Record last verified: 2016-01

Locations

US (1)