Combining immune therapy and cryoablation for triple-negative breast cancer treatment

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.

This study is testing if combining a freezing treatment with an immune therapy can help women with triple-negative breast cancer live longer without their cancer coming back after initial chemotherapy.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: University of Texas Southwestern Medical Center (other)
• Drugs / interventions: nivolumab, ipilimumab, pembrolizumab, chemotherapy
• Locations: 4 sites (Los Angeles, California and 3 other locations)
• Trial ID: NCT03546686 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the effects of pre-operative cryoablation and immune checkpoint inhibition on three-year Event Free Survival in women with triple-negative breast cancer who have residual disease after taxane-based neoadjuvant chemotherapy. The approach involves using cryoablation to induce immune responses by destroying tumor tissue, followed by the administration of Pembrolizumab, an FDA-approved immune checkpoint inhibitor. Eligible participants will undergo either mastectomy or breast-conserving surgery after these interventions.

Who should consider this trial

Good fit: Ideal candidates are women aged 18 and older with confirmed triple-negative breast cancer that is operable and has not metastasized.

Not a fit: Patients with distant metastases or those whose tumors are not amenable to cryoablation may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve event-free survival rates for women with triple-negative breast cancer.

How similar studies have performed: Other studies have shown promise with immune checkpoint inhibitors in breast cancer, but the combination with cryoablation is a novel approach.

Eligibility criteria

Inclusion 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.

Exclusion Criteria:

* 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

Where this trial is running

Los Angeles, California and 3 other locations

• Cedars Sinai Medical Center — Los Angeles, California, United States (ACTIVE_NOT_RECRUITING)
• Ohio State University Medical Center — Columbus, Ohio, United States (RECRUITING)
• Providence Cancer Institute — Portland, Oregon, United States (ACTIVE_NOT_RECRUITING)
• UT Southwestern Medical Center — Dallas, Texas, United States (RECRUITING)

Study contacts

• Principal investigator: Heather McArthur, MD — UT Southwestern Medical Center
• Study coordinator: Meredith Carter, MS

Conditions: Breast Cancer, Hormone Receptor Negative, Her2- Negative, Resectable Breast Cancer, breast cancer, immunotherapy, Ipilimumab, Nivolumab