Overview

Anastrazole, Fulvestrant & Abemaciclib for HR+HER2- Metastatic Breast Cancer

Status:
Not yet recruiting
Trial end date:
2028-12-31
Target enrollment:
0
Participant gender:
All
Summary
This is a phase 2, open-label, singled-arm clinical trial determining efficacy of combination therapy with anastrozole, fulvestrant and abemaciclib in subjects with breast cancer. These are subjects who are newly diagnosed advanced or metastatic hormone receptor positive breast cancer or subjects who have progressed following treatment free interval of more than 12 months following adjuvant or neoadjuvant treatment.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
University of California, Irvine
Treatments:
Anastrozole
Fulvestrant
Criteria
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/College of American Pathologists Guidelines: For
ER and PgR assays to be considered positive, ≥1% of tumor cell nuclei must be
immunoreactive by immunohistochemistry (IHC)

- Patients must have newly diagnosed metastatic regional breast cancer (Stage IV per
AJCC 8th edition criteria for staging of breast cancer) or local-regional advanced or
recurrent cancer not amenable to curative treatment

- Relapse > 12 months from completion of (neo)adjuvant endocrine and/or chemotherapy
with no treatment for advanced or metastatic disease

- Age ≥ 18 years

- ECOG performance status 0-2

- Have post-menopausal status as defined by following: Prior bilateral oophorectomy. Age
≥ 60 years, 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.
If patients are pre-menopausal ovarian function suppression will be initiated.

- 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. 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

2. Absolute neutrophil count ≥1,500/mcL

3. Platelets ≥ 100,000/mcl

4. 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

5. AST (SGOT)/ALT (SPGT) ≤ 2.5 X institutional ULN

6. Creatinine ≤ 1.5 X institutional ULN

- Able to swallow oral medications

- 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 12 months is required between last chemotherapy dose and enrollment (provided
the patient did not receive radiotherapy).

- Patients with visceral metastasis including brain metastasis are included

- If patients have been treated with prior Neo-Adjuvant chemotherapy >12 months ago,
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

- Women of child-bearing potential and men must agree to use ovarian or testicular
suppression prior to study entry, for the duration of study participation, and for 90
days following completion of therapy. Should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her treating physician
immediately

- A female of child-bearing potential is any woman (regardless of sexual orientation,
having undergone a tubal ligation, or remaining celibate by choice) who meets the
following criteria:

1. Has not undergone a hysterectomy or bilateral oophorectomy; or

2. Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,
has had menses at any time in the preceding 12 consecutive months)

Exclusion Criteria:

- Localized breast cancer which is curable with surgery or radiation, with or without
chemotherapy. 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. 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 (Rumi,
Sato et al.) as defined in the relevant ASCO/CAP guidelines

- Inflammatory breast cancer

- Patients who have had endocrine therapy, chemotherapy or radiotherapy within 12 months
prior to entering the study

- Prior treatment with any CDK 4/6 inhibitor and/or Fulvestrant

- Patients 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 serious pre-existing 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, or
psychiatric illness/social situations that would limit compliance with study
requirements)

- 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.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to CDK4/6 inhibitors or other agents used in study.

- Patients who are pregnant or nursing due to the potential for congenital abnormalities
and the potential of this regimen to harm nursing infants.