Clinical trial NCT04614194: Single Cell Immune and Non-immune Correlates of Response to Neoadjuvant Abemaciclib
Official title: Single Cell Immune and Non-immune Correlates of Response to Neoadjuvant Abemaciclib and Letrozole in Hormone Receptor Positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
name: Cancer Prevention Research Institute of Texas
First posted: 2020-11-03
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to better understand how the immune system plays a role in fighting breast cancer and specifically research if the immune system response against breast cancer can be improved with endocrine therapy and cyclin dependent kinase inhibitor therapy in patients with hormone receptor positive breast cancer. This will be studied by collecting tumor tissue and blood samples before and after 2 weeks of study treatment with commonly used endocrine therapy and cyclin dependent kinase inhibitor therapy.


Eligibility criteria: INCLUSION CRITERIA:

* Clinical stage operable stage I, II, or III invasive mammary carcinoma, which is estrogen receptor or progesterone receptor positive by immunohistochemistry and HER2 negative by Herceptest (0 or 1+) or not amplified by in situ hybridization as per routine clinical testing.
* Have post-menopausal status, as defined by any of the following: Subjects at least 55 years of age OR Subjects under 55 years of age and amenorrheic for at least 12 months OR follicule stimulating hormone (FSH) values ≥ 40 IU/L and estradiol levels ≤ 40 pg/mL (140 pmol/L) or in postmenopausal ranges per local or institutional reference ranges.
* Breast tumor ≥1cm in diameter by either physical exam or ultrasound and suitable for pre and post-treatment tissue sampling.
* Meet either of 2 following criteria, for which neoadjuvant endocrine therapy for 2 weeks is deemed suitable: 1) disease that is planned for surgery as initial therapy, in which 2 weeks of neoadjuvant endocrine therapy is deemed suitable, 2) Disease for which neoadjuvant systemic therapy (either chemotherapy or endocrine therapy) may be planned, in which 2 weeks of neoadjuvant endocrine therapy prior to start of systemic therapy is deemed suitable.
* At least 18 years of age
* Performance status ECOG ≤ 2
* Have adequate organ function (ANC ≥1,500/mcL, Platelets ≥100,000/mcL, Hemoglobin ≥8 g/dL, Total bilirubin ≤1.5 × upper limit of normal, ALT and AST ≤3 × upper limit of normal, Creatinine clearance \>30 mL/minute
* The patient is able to swallow oral medications
* Patients with a prior history of contralateral breast cancer are eligible if they have no evidence of recurrence of their initial primary breast cancer.
* Women may have been taking tamoxifen or raloxifene as a preventive agent prior to study entry but must have discontinued the drug for at least 28 days prior to study enrollment.
* Subjects have ended hormone replacement therapy at least 7 days prior to receiving the first dose of randomized therapy.
* Ability to understand and the willingness to sign a written informed consent.
* A female of childbearing potential, must have a negative serum pregnancy test within 7 days of the first dose of abemaciclib and agree to use a highly effective contraception method during the treatment period and for 3 weeks following the last dose of abemaciclib. These criteria should not apply to most or all patients on the trial given the inclusion criteria is for post-menopausal patients only who should not be of childbearing potential.

Note: Contraceptive methods may include an intrauterine device \[IUD\] or barrier method. If condoms are used as a barrier method, a spermicidal agent should be added as a double barrier protection. Cases of pregnancy that occur during maternal exposures to abemaciclib should be reported. If a patient or spouse/partner is determined to be pregnant following abemaciclib initiation, she must discontinue treatment immediately. Data on fetal outcome and breast-feeding are to be collected for regulatory reporting and drug safety evaluation.

EXCLUSION CRITERIA:

* Active metastatic breast cancer, inflammatory breast cancer, or locally recurrent breast cancer.
* The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea).
* Females who are pregnant, lactating, or premenopausal.
* Severe uncontrolled malabsorption condition or disease (i.e. grade 2 or higher diarrhea, severe malnutrition, short gut syndrome).
* Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
* Chemotherapy, radiotherapy, or any other cancer therapy for current diagnosis of breast cancer.
* Subjects may not have received or be receiving any other investigational agents for the treatment of the cancer under study.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to abemaciclib or other agents used in study.
* Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.

Primary outcomes:
measure: Change in T cell activation
timeFrame: After treatment ends (14 (+/- 3) days
Secondary outcomes:
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Parkland Hospital
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: University of Texas Southwestern Medical Center
name: Sangeetha Reddy, MD
role: PRINCIPAL_INVESTIGATOR
References: