RECRUITING

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

Conditions

Breast Cancer Hormone Receptor Negative Her2- Negative Resectable Breast Cancer immunotherapy Ipilimumab Nivolumab Cryoablation

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to determine the impact of pre-operative cryoablation, and immune checkpoint inhibition (ICI) 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.

Official Title

A Single Arm Phase 2 Study of Peri-Operative Immune Checkpoint Inhibition and Cryoablation in Women with Hormone Receptor-Negative, HER2-Negative Early Stage/Resectable Breast Cancer.

Quick Facts

Study Start:2019-11-12

Study Completion:2028-06

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03546686

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:FEMALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Women age 18 years or older 2. Confirmed histologic diagnosis of invasive carcinoma of the breast 3. Pathology confirmation of invasive carcinoma (reported or requested and pending) 4. 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. 5. Operable tumor measuring ≥1.0 cm in maximal diameter 6. Any nodal status allowed, including negative nodal status. 7. Multifocal and multicentric disease is permitted if all foci have been biopsied and also meet the criteria for TNBC. 8. Synchronous bilateral invasive breast cancer is permitted if all foci have been biopsied and also meet the criteria for TNBC. 9. No indication of distant metastases 10. Total mastectomy or lumpectomy planned 11. Tumor amenable to cryoablation as determined by a study radiologist 12. ECOG performance status score of 0 or 1. 13. 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) 14. 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. 15. 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 16. Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.	* Medical history and concurrent diseases 1. 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. 2. 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. 3. 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. 4. Has known active hepatitis B or hepatitis C. * Prohibited Treatments and/or Therapies 1. 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. 2. Any non-oncology live vaccine therapy used for prevention of infectious diseases within 3 weeks prior to first dose of ICI. 3. Prior investigational agents within 3 weeks prior to ICI administration

Inclusion Criteria

Exclusion Criteria

1. Women age 18 years or older
2. Confirmed histologic diagnosis of invasive carcinoma of the breast
3. Pathology confirmation of invasive carcinoma (reported or requested and pending)
4. 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.
5. Operable tumor measuring ≥1.0 cm in maximal diameter
6. Any nodal status allowed, including negative nodal status.
7. Multifocal and multicentric disease is permitted if all foci have been biopsied and also meet the criteria for TNBC.
8. Synchronous bilateral invasive breast cancer is permitted if all foci have been biopsied and also meet the criteria for TNBC.
9. No indication of distant metastases
10. Total mastectomy or lumpectomy planned
11. Tumor amenable to cryoablation as determined by a study radiologist
12. ECOG performance status score of 0 or 1.
13. 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)
14. 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.
15. 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
16. Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.

* Medical history and concurrent diseases
1. 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.
2. 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.
3. 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.
4. Has known active hepatitis B or hepatitis C.
* Prohibited Treatments and/or Therapies
1. 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.
2. Any non-oncology live vaccine therapy used for prevention of infectious diseases within 3 weeks prior to first dose of ICI.
3. Prior investigational agents within 3 weeks prior to ICI administration

Contacts and Locations

Study Contact

Meredith Carter, MS

CONTACT

214-648-7097

Meredith.carter@utsouthwestern.edu

Principal Investigator

Heather McArthur, MD

PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Study Locations (Sites)

Cedars Sinai Medical Center

Los Angeles, California, 90048

United States

Ohio State University Medical Center

Columbus, Ohio, 43210

United States

Providence Cancer Institute

Portland, Oregon, 97213

United States

UT Southwestern Medical Center

Dallas, Texas, 75390

United States

Collaborators and Investigators

Sponsor: University of Texas Southwestern Medical Center

Heather McArthur, MD, PRINCIPAL_INVESTIGATOR, UT Southwestern Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-11-12

Study Completion Date2028-06

Study Record Updates

Study Start Date2019-11-12

Study Completion Date2028-06

Terms related to this study

Keywords Provided by Researchers

Hormone Receptor Negative
Her2- Negative
Resectable Breast Cancer
breast cancer
immunotherapy
Ipilimumab
Nivolumab
Cryoablation

Additional Relevant MeSH Terms

Breast Cancer