Neo-Adjuvant Abemaciclib With Fulvestrant in Patients With ER/PR +HER Negative Breast Cancer

May 9, 2023 updated by: Ritesh Parajuli, University of California, Irvine

A Phase II Open Label Trial of Neo-Adjuvant Abemaciclib With Fulvestrant in Patients Who Develop Localized Recurrence While on Adjuvant Endocrine Therapy With Molecular Evidence of Endocrine Resistance

This is a phase 2 single-arm, open-label determining efficacy of Neo-adjuvant Abemaciclib and Fulvestrant in subjects with Hormone receptor positive patients with localized non-metastatic breast cancer who develop local recurrence while on adjuvant endocrine therapy with molecular evidence of endocrine resistance.

Study Overview

Study Type

Interventional

Enrollment (Actual)

1

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Orange, California, United States, 92868
        • Chao Family Comprehensive Cancer Center, University of California, Irvine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients must have a diagnosis of HR+ breast cancer. To fulfill the requirement of HR+ disease, a breast cancer must express, by immunohistochemistry (IHC), at least one of the hormone receptors (ER, progesterone receptor [PgR]) as defined in the relevant American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Guidelines (Hammond et al. 2010):

    1. For ER and PgR assays to be considered positive, ≥1% of tumor cell nuclei must be immunoreactive by immunohistochemistry (IHC) (Hammond et al. 2010).

  • Patients must have Loco regional breast cancer (Stage I, Stage II and stage III per AJCC 8th edition criteria for staging of breast cancer)
  • Patients must have localized recurrence while on adjuvant endocrine therapy
  • Patients must have any known molecular evidence of endocrine resistance by next generation sequencing
  • Age ≥ 18 years.
  • ECOG performance status 0-1
  • Have post-menopausal status as defined by following:

    1. Prior bilateral oophorectomy
    2. Age ≥ 60 years
    3. Age < 60 and amenorrheic (non-treatment-induced amenorrhea secondary to tamoxifen, toremifene, ovarian suppression, or chemotherapy) for at least 12 months. Follicle-stimulating hormone (FSH) and estradiol must be in the postmenopausal range.
  • Have at least one measurable disease as defined per RECIST 1.1
  • Adequate organ and marrow function as defined below:

    1. Hemoglobin* > 8 g/dL
    2. Absolute neutrophil count ≥ 1,500/mcL
    3. Total bilirubin ≤ 1.5 X institutional ULN, Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted
    4. AST (SGOT)/ALT (SPGT) ≤ 2.5 X institutional ULN
    5. Creatinine ≤ 1.5 X institutional ULN

      1. *Patients may receive transfusion of packed red blood cells (PRBC) to achieve this hemoglobin level at the discretion of the investigator; however, initial study drug treatment must not begin earlier than the day after the PRBC transfusion.
  • Able to swallow oral medications
  • Patients who received adjuvant radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and screening for the study.
  • Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to enrollment. A washout period of at least 21 days is required between last chemotherapy dose and enrollment (provided the patient did not receive radiotherapy).
  • Any known markers of response or resistance to CDK 4/6 inhibitors to be present in the biopsy specimen
  • If patients have been treated with prior Neo-Adjuvant chemotherapy at the time of primary diagnosis and not at the time of recurrence, they will be included in the study.
  • Must be able to sign a written informed consent, are reliable, willing to be available for the duration of the study and are willing to follow study procedures

Exclusion Criteria:

  • Stage IV metastatic breast cancer

    1. This study will utilize the American Joint Committee on Cancer (AJCC) staging system, eight edition that provides a strategy for grouping patients with respect to prognosis. The AJCC has designated staging by TNM classification. The researchers will also review tumor size, lymph node status, and estrogen-receptor and progesterone-receptor levels in the tumor tissue.

  • Patients with HER2 positive and triple negative breast cancer

    1. To fulfill the requirement of HER2- and Triple negative disease, a breast cancer must not demonstrate, at initial diagnosis or upon subsequent biopsy, overexpression of HER2 or should not express ER or PR receptors by either IHC or in-situ hybridization (ISH) as defined in the relevant ASCO/CAP guidelines (Wolff et al. 2013).

  • Inflammatory breast cancer
  • Newly diagnosed endocrine naïve patients
  • No molecular evidence of endocrine resistance
  • Prior treatment with any CDK 4/6 inhibitor and/or Fulvestrant
  • Pre-menopausal women
  • Are currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study. If a patient is currently enrolled in a clinical trial involving non-approved use of a device, then agreement with the principal investigator is required to establish eligibility
  • Have had major surgery within 14 days prior to enrollment to allow for post-operative healing of the surgical wound
  • Have initiated bisphosphonates or approved RANK ligand therapy for breast cancer with osseous metastasis, if patients are received Zolendronic acid or Denosumab in the adjuvant manner then such patients will be allowed participate
  • Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (for example, history of major surgical resection involving the stomach or small bowel or preexisting Crohn's disease or ulcerative colitis , interstitial lung disease, severe dyspnea at rest, any pre-existing chronic condition resulting in baseline grade 2 or higher diarrhea)
  • Have a personal history of any of the following conditions: syncope or cardiovascular etiology, ventricular tachycardia, ventricular fibrillation or sudden cardiac arrest
  • Have a history of any other cancer (except for non-melanoma skin cancer or carcinoma in situ of the cervix) unless in complete remission with no therapy for a minimum of three years or have received an autologous or allogeneic stem-cell transplant
  • Have an active bacterial or fungal infection or a detectable viral infection (for example HIV or viral hepatitis). Screening is not required for enrollment
  • Recent therapy with a biologic agent or a monoclonal therapy is excluded. Wash out of at least three half-lives of monoclonal antibody would be required to be enrolled.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Abemaciclib and Fulvestrant
Abemaciclib will be administered orally at the dose of 150 mg twice daily. Fulvestrant will be administered intramuscularly at an initial loading dose of 500mg on days 1 and 15 of the first cycle and then 500 mg intramuscularly every first day of each subsequent cycle. One cycle is 28 days.
Given PO
Other Names:
  • VERZENIO™
Given Intramuscularly
Other Names:
  • FASLODEX®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With a Pathological Complete Response
Time Frame: From start of study treatment to surgery, on average we expect 6 months.
This is defined as the percentage of subjects who achieve a pathological complete response (pCR). A pCR is defined by no evidence of tumor cells in the final surgical specimen.
From start of study treatment to surgery, on average we expect 6 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate
Time Frame: From start of study treatment to surgery, on average we expect 6 months.
To assess the overall response rate to the combination of Abemaciclib and Fulvestrant. Overall response rate (ORR) is defined as confirmed complete response (CR) and partial response (PR). Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1): Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions. ORR = CR + PR
From start of study treatment to surgery, on average we expect 6 months.
Recurrence Disease Free Survival
Time Frame: Up to 5 years
Recurrence disease free survival will be defined as the time from surgery until patient develops recurrence.
Up to 5 years
Percentage of Grade 3-5 Adverse Events
Time Frame: From start of study treatment to surgery, on average we expect 6 months.
To evaluate the safety and tolerability of administering Abemaciclib and Fulvestrant. Toxicity and adverse events are based on the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0.
From start of study treatment to surgery, on average we expect 6 months.
Preoperative Endocrine Prognostic Index Score
Time Frame: From start of study treatment to surgery, on average we expect 6 months.
The preoperative endocrine prognostic index (PEPI) Score is a score that is used in clinical trials to assess response to Neo-Adjuvant endocrine therapy. The PEPI score takes into account the tumor and nodal stage, level of ER expression and Ki 67 following neoadjuvant endocrine therapy.
From start of study treatment to surgery, on average we expect 6 months.
Percentage of Participants Who Undergo Breast Conserving Surgery
Time Frame: From start of study treatment to surgery, on average we expect 6 months.
This is defined as the percentage of subjects who undergo breast conserving surgery after receiving Abemaciclib and Fulvestrant
From start of study treatment to surgery, on average we expect 6 months.
Percentage Change in Ki 67
Time Frame: From start of study treatment to surgery, on average we expect 6 months.
Percentage change in the Ki 67 will be evaluated from baseline to the treated specimen after breast surgery
From start of study treatment to surgery, on average we expect 6 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: Ritesh Parajuli, MD, Chao Family Comprehensive Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 23, 2020

Primary Completion (Actual)

February 16, 2022

Study Completion (Actual)

February 16, 2022

Study Registration Dates

First Submitted

March 9, 2020

First Submitted That Met QC Criteria

March 9, 2020

First Posted (Actual)

March 12, 2020

Study Record Updates

Last Update Posted (Actual)

June 6, 2023

Last Update Submitted That Met QC Criteria

May 9, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Breast Neoplasm

Clinical Trials on Abemaciclib

3
Subscribe