Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04614194
Recruitment Status : Not yet recruiting
First Posted : November 3, 2020
Last Update Posted : March 29, 2021
Sponsor:
Collaborators:
Eli Lilly and Company
Cancer Prevention Research Institute of Texas
Information provided by (Responsible Party):
Sangeetha Reddy, University of Texas Southwestern Medical Center

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Letrozole Drug: Abemaciclib Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Single Cell Immune and Non-immune Correlates of Response to Neoadjuvant Abemaciclib and Letrozole in Hormone Receptor Positive Breast Cancer
Estimated Study Start Date : July 15, 2021
Estimated Primary Completion Date : December 22, 2023
Estimated Study Completion Date : December 22, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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.
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.

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




Primary Outcome Measures :
  1. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04614194


Contacts
Layout table for location contacts
Contact: Melanie Hullings 214-648-7097 Melanie.Hullings@UTSouthwestern.edu

Locations
Layout table for location information
United States, Texas
Parkland Hospital
Dallas, Texas, United States, 75039
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Eli Lilly and Company
Cancer Prevention Research Institute of Texas
Investigators
Layout table for investigator information
Principal Investigator: Sangeetha Reddy, MD University of Texas Southwestern Medical Center
Layout table for additonal information
Responsible Party: Sangeetha Reddy, Assistant Professor, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT04614194    
Other Study ID Numbers: STU-2020-1043
First Posted: November 3, 2020    Key Record Dates
Last Update Posted: March 29, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs