Breast Cancer Clinical Trial

Peri-Operative Immune Checkpoint Inhibition and Cryoablation in Women With Triple-negative Breast Cancer

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.

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Full Description

The purpose of this study is to determine the impact of pre-operative cryoablation, immune checkpoint inhibition (ICI) on 3-year Event Free Survival (EFS), in women with triple negative breast cancer after taxane-based neoadjuvant chemotherapy. Our strategy combines two interventions: induced activation and maturation of dendritic cells and tumor-specific T cells by cross-presentation of tumor antigens via local destruction of tumor tissue by cryoablation. Second, we administer Pembrolizumab, an antibody that inhibits lymphocyte programmed death 1 (PD-1) receptors and interferes with PD-1 mediated T-cell regulatory signaling; and was recently US FDA approved as curative-intent standard-of-care treatment for triple negative breast cancer. Women with residual triple negative resectable breast cancer after neoadjuvant chemotherapy will be treated with tumor cryoablation and pre-operative immune checkpoint inhibition (ICI). Women undergoing either mastectomy or breast conserving surgery are eligible.

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Eligibility 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 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.

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.
A history of invasive malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer, or ovarian cancer.
Has known active hepatitis B or hepatitis C.

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 ICI.
Prior investigational agents within 3 weeks prior to ICI administration

Study is for people with:

Breast Cancer

Phase:

Phase 2

Estimated Enrollment:

80

Study ID:

NCT03546686

Recruitment Status:

Recruiting

Sponsor:

University of Texas Southwestern Medical Center

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There are 4 Locations for this study

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Cedars Sinai Medical Center
Los Angeles California, 90048, United States More Info
Nikki Kem-Bernard
Contact
[email protected]
Monica Mita, MD
Principal Investigator
Ohio State University Medical Center
Columbus Ohio, 43210, United States More Info
Angela Campbell
Contact
614-293-4208
Margaret Gatti-Mays, MD
Principal Investigator
Providence Cancer Institute
Portland Oregon, 97213, United States More Info
Tracy Kelly
Contact
503-215-3915
[email protected]
David Page, MD
Principal Investigator
UT Southwestern Medical Center
Dallas Texas, 75390, United States More Info
Meredith Carter, MS
Contact
214-648-7097
[email protected]

How clear is this clinincal trial information?

Study is for people with:

Breast Cancer

Phase:

Phase 2

Estimated Enrollment:

80

Study ID:

NCT03546686

Recruitment Status:

Recruiting

Sponsor:


University of Texas Southwestern Medical Center

How clear is this clinincal trial information?

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