Single Cell Immune and Non-immune Correlates of Response to Neoadjuvant Abemaciclib

• ClinicalTrials.gov Identifier: NCT04614194
• Recruitment Status: Recruiting
• First Posted: November 3, 2020
• Last Update Posted: May 29, 2023
• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: Eli Lilly and Company; Cancer Prevention Research Institute of Texas
• Information provided by (Responsible Party): Sangeetha Reddy, University of Texas Southwestern Medical Center

Tracking Information

• First Submitted Date: October 13, 2020
• First Posted Date: November 3, 2020
• Last Update Posted Date: May 29, 2023
• Actual Study Start Date: April 15, 2021
• Estimated Primary Completion Date: April 15, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 2, 2020)

Change in T cell activation [ Time Frame: After treatment ends (14 (+/- 3) days ]

Change in T cell activation between matched pre-treatment and on-treatment tissue samples of responder patients treated with abemaciclib and letrozole. T cell activation will be defined as the density of granzyme positive CD8 T cells detected on multiplex immunohistochemistry. Responders are defined as having complete cell cycle arrest by Ki-67.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Breast Cancer

Intervention

• Drug: Letrozole
  Oral. Tablets should be taken at the same times every day, with or without food.
• Drug: Abemaciclib
  Oral. Tablets should be taken at the same times every day, with or without food.

Study Arms

• Experimental: Arm A: Abemaciclib + Letrozole
  Patient will take twice daily abemaciclib and daily letrozole (Arm A) for 2 weeks prior to your planned standard treatment for breast cancer. In addition to tests and procedures that are part of your standard care, you will have a biopsy and blood draw for study purposes prior to starting study treatment.
  Interventions:

  • Drug: Letrozole
  • Drug: Abemaciclib
• Experimental: Arm B: Letrozole
  Patient will take daily letrozole only (Arm B) according to treatment arm for 2 weeks prior to your planned standard treatment for breast cancer. In addition to tests and procedures that are part of your standard care, you will have a biopsy and blood draw for study purposes prior to starting study treatment.
  Intervention: Drug: Letrozole

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 2, 2020): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 15, 2025
• Estimated Primary Completion Date: April 15, 2024 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Shahbano Shakeel; 214-648-7097; Shahbano.Shakeel@UTSouthwestern.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04614194
• Other Study ID Numbers: STU-2020-1043
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Sangeetha Reddy, University of Texas Southwestern Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Texas Southwestern Medical Center
• Original Study Sponsor: Same as current

Collaborators

• Eli Lilly and Company
• Cancer Prevention Research Institute of Texas

Investigators

• Principal Investigator: Sangeetha Reddy, MD; University of Texas Southwestern Medical Center

• PRS Account: University of Texas Southwestern Medical Center
• Verification Date: May 2023