Clinical Trials /

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

NCT04614194

Description:

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.

Related Conditions:
  • Invasive Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: STU-2020-1043
  • NCT ID: NCT04614194

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
LetrozoleArm A: Abemaciclib + Letrozole
AbemaciclibArm A: Abemaciclib + Letrozole

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Arm A: Abemaciclib + LetrozoleExperimentalPatient 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.
  • Letrozole
  • Abemaciclib
Arm B: LetrozoleExperimentalPatient 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.
  • Letrozole

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.

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in T cell activation
Time Frame:After treatment ends (14 (+/- 3) days
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Texas Southwestern Medical Center

Last Updated

March 29, 2021