Clinical trial NCT06246786: Breast/Cyclosporin A/TNBC (Triple Negative Breast Cancer)
Official title: A Pre-Surgical Window of Opportunity Trial Investigating the Effect of Cyclosporin A on Triple Negative Breast Cancer With Defective DNA Repair
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Triple Negative Breast Cancer
DNA Damage Repair Deficiency
Keywords: Defective DNA repair
RAD51
Cyclosporine
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
First posted: 2024-02-07
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This will be a single arm, non-randomized, pre-surgical clinical trial
Primary purpose: TREATMENT

Brief summary: This will be a single arm, non-randomized, pre-surgical clinical trial of women with newly diagnosed triple negative breast cancer with high g-H2Ax (gamma H2AX antibodies) comparing changes in biomarkers from a diagnostic core needle biopsy to surgical pathology specimen or repeat core needle biopsy.

Detailed description: Patients that are able to be in the study will be asked if they would like to be in the study on their first visit with their medical doctor. Lab work including a complete blood count and complete metabolic panel will be drawn at this time as part of their standard of care work-up. If patients choose to be in the study, they will then sign consent and then have the study drug dispensed on day 1 after a blood sample has being collected. No extra physician visit will be needed to join in the study. Patients will then take the study drug, CsA, until the day before surgery. Mastectomy (breast removal) or lumpectomy (lump removal) is the standard of care for early-stage breast cancer.

Surgery takes about three weeks to schedule, therefore we expect that patient's will take the study medication for between 14 and 30 days. There will be no delays in the standard of care surgery. There will be weekly visits and/or phone calls on Days 8, 15 and 21-30 to get feedback on any adverse effects and how the subject is dealing with changing the dosage, with any changes made to treatment as needed. The patients will stop taking the Cyclosporin (CsA) the day before surgery. Within two weeks after surgery, after the patient has been off drug, they will be questioned, and an assessment of adverse events will be done.

Eligibility criteria: Inclusion Criteria:

* Participants may be female or male who are 18 years old or older. Ability to consent to treatment - patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
* Previously untreated invasive breast cancer determined by a core needle biopsy.
* Prior, unrelated, breast cancer is allowed.
* Stage I-III breast cancer will be included that are Estrogen receptor and or progesterone receptor 0-10%, human epidermal growth factor receptor 2 (HER2) negative defined as per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP guidelines). HER2 of 2+ on Immunohistochemistry (IHC) should have a ratio of less than 2.0 on fluorescence in situ hybridization (FISH) testing to be considered HER2 negative
* Patients must have low or negative RAD51 immunohistochemistry (defined as median \<5 foci per nucleus after measuring at least 200 cells)
* Patients must be able to take oral medications. Patients may not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the study drug.
* Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (β-hCG) pregnancy test result within 14 days prior to the first dose of CsA.
* Women of childbearing potential and men should have an adequate mode of contraception to be eligible for this trial.
* Patients must be eligible for surgical resection of their breast cancer or repeat biopsy after completing treatment.
* Patients must have a complete history and physical examination within 30 days prior to registration.
* Patients must have a performance status of Eastern Cooperative Oncology Group (ECOG) 0, 1, or 2.
* Tissue block of initial biopsy specimen is available.
* Patient may not be concurrently enrolled in another investigational drug treatment study.

Exclusion Criteria:

* Renal impairment defined as estimated glomerular filtration rate (EGFR) \<30
* Hepatic impairment as judged by clinical investigator or bilirubin \>2
* As judged by the investigator, severe uncontrolled concurrent medical conditions, psychiatric illness, or social condition that would limit compliance with study requirements
* Known hypersensitivity to CsA
* Current use of calcium channel blockers, antifungals, azithromycin, clarithromycin, erythromycin, methylprednisolone, allopurinol, amiodarone, metoclopramide, bromocriptine, colchicine, oral contraceptives, nafcillin, rifampin, phenytoin, octreotide, phenobarbital, carbamazepine, St John's Wort, HIV protease inhibitors
* Inflammatory breast cancer
* Uncontrolled hypertension
* Pregnant or breast-feeding women. As there have been no well-controlled studies conducted with pregnant women to determine the effect of CsA on the fetus. However, there have been clinical reports of congenital malformations associated with the use of the drug.
* Patients who will receive neoadjuvant chemotherapy for their triple negative breast cancer are not eligible for this clinical trial.

Primary outcomes:
measure: Ki67 Expression
timeFrame: 6 weeks
Secondary outcomes:
measure: Changes in g-H2Ax
timeFrame: 6 weeks
measure: Changes in apoptosis markers
timeFrame: 6 weeks
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Mays Cancer Center, UT Health San Antonio
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center at San Antonio
name: Virginia Kaklamani, MD, DSc
role: PRINCIPAL_INVESTIGATOR
References: