A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study of Fulvestrant with or without Abemaciclib in HR+, HER2- Advanced Breast Cancer

Trial ID: 2023-506781-30-00
Protocol: I3Y-MC-JPBL
Sponsor: Eli Lilly & Co.

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Diseases & Conditions

Breast cancer

Objectives

The primary objective of the study is to compare the efficacy of **abemaciclib** (LY2835219) in combination with **fulvestrant** versus placebo combined with fulvestrant in terms of progression-free survival (PFS) for women diagnosed with hormone receptor-positive (HR+), HER2-negative locally advanced or metastatic **breast cancer**. This comparison is clinically relevant as it aims to determine the potential benefit of adding abemaciclib, a CDK4/6 inhibitor, to the standard treatment regimen, which could lead to improved management and outcomes for this patient population.

Participants

The clinical trial involves a total of **46 participants** diagnosed with **breast cancer**, specifically focusing on women with HR+, HER2- locally advanced or metastatic breast cancer. The study population is exclusively female, with an age range corresponding to categories 3 and 4, indicating adult and elderly participants. Participants were selected based on specific criteria, including postmenopausal status due to surgical or natural menopause or ovarian suppression, and a performance status of 0 or 1 on the ECOG scale. The trial excludes male subjects and includes a vulnerable population. Participants must have discontinued previous cancer therapies and recovered from acute effects before receiving the study drug. Lifestyle considerations such as diet and physical activity are not specified in the available data.

Plans and Procedures

The clinical trial is designed as a **randomized, double-blind, placebo-controlled, Phase 3 study** to evaluate the efficacy of **fulvestrant** with or without **abemaciclib** in women with hormone receptor-positive, HER2-negative locally advanced or metastatic **breast cancer**. The primary objective is to compare the progression-free survival (PFS) between the treatment groups. The trial is expected to run from July 22, 2014, to December 30, 2024, with a maximum treatment period of 942 days for participants.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as postmenopausal status, disease progression, and performance status. Following randomization, participants will receive either the investigational treatment or placebo. Study visits will include regular follow-up assessments to monitor safety, efficacy, and disease progression. The end-of-study visit will occur after the completion of the treatment period or upon early termination.

The expected length of participant involvement is approximately 31 months, contingent upon individual response and disease progression. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or disease progression that necessitates alternative treatment. The trial is categorized as low-intervention, as the investigational products are authorized in the EU and used in accordance with their marketing authorization, posing minimal additional risk to participants.

Treatment

The clinical trial involves the administration of **fulvestrant**, a chemical substance classified under the ATC code L02BA03. Fulvestrant is provided in the pharmaceutical form of a solution for injection. The maximum daily dose is 500 mg/ml, with a total maximum dose of 16,500 mg/ml over the treatment period. The administration route is via injection, and the treatment duration is set for a maximum of 942 days. Fulvestrant is utilized as part of endocrine therapy in this study.

Additionally, the trial includes the use of **abemaciclib**, a chemical compound identified by the ATC code L01EF03. Abemaciclib is administered orally in the form of tablets, with a maximum daily dose of 300 mg and a total maximum dose of 282,600 mg over the treatment period. The treatment duration for abemaciclib is also set for a maximum of 942 days. This medication is part of the targeted therapy regimen in the study. It is important to note that abemaciclib is provided in clinical trial-specific packaging, differing from its standard marketing authorization packaging.

In this randomized, double-blind, placebo-controlled, Phase 3 study, the primary objective is to compare the efficacy of the combination of fulvestrant and abemaciclib versus fulvestrant with a placebo in women with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol.

Efficacy

The efficacy of the clinical trial will be assessed primarily through the evaluation of **Progression-Free Survival (PFS)**. This endpoint is designed to compare the efficacy of the combination of LY2835219 (abemaciclib) plus fulvestrant versus placebo plus fulvestrant in women with hormone receptor-positive (HR+), HER2-negative locally advanced or metastatic breast cancer. The trial is structured as a randomized, double-blind, placebo-controlled, Phase 3 study. The measurement of PFS will be conducted at specified intervals throughout the trial duration, although specific timepoints for these assessments are not detailed in the provided data. The trial aims to determine whether the addition of abemaciclib to fulvestrant therapy can significantly improve PFS compared to fulvestrant alone. The study will adhere to rigorous clinical trial protocols to ensure the accuracy and reliability of the efficacy data collected.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Have a diagnosis of HR+, HER2- breast cancer
Have locally advanced disease not amenable to curative treatment by surgery or metastatic disease. In addition, participants must fulfill 1 of the following criteria: - relapsed with radiologic evidence of progression while receiving neoadjuvant or adjuvant endocrine therapy, with no subsequent endocrine therapy received following progression - relapsed with radiologic evidence of progression within 1 year from completion of adjuvant endocrine therapy, with no subsequent endocrine therapy received following progression - relapsed with radiologic evidence of progression more than 1 year from completion of adjuvant endocrine therapy and then subsequently relapsed with radiologic evidence of progression after receiving treatment with either an antiestrogen or an aromatase inhibitor as firstline endocrine therapy for metastatic disease. Patients may not have received more than 1 line of endocrine therapy or any prior chemotherapy for metastatic disease - presented de novo with metastatic disease and then relapsed with Radiologic evidence of progression after receiving treatment with either an antiestrogen or an aromatase inhibitor as first-line endocrine therapy for metastatic disease. Patients may not have received more than 1 line of endocrine therapy or any prior chemotherapy for metastatic disease
Have postmenopausal status due to either surgical/natural menopause or ovarian suppression (initiated at least 28 days prior to Day 1 of Cycle 1) with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin
Have a negative serum pregnancy test at baseline (within 14 days prior to randomization) and agree to use medically approved precautions to prevent pregnancy during the study and for 12 weeks following the last dose of Abemaciclib if postmenopausal status is due to ovarian suppression with a GnRH agonist
Have either measurable disease or nonmeasurable bone only disease
Have a performance status ≤1 on the ECOG scale
Have discontinued previous therapies for cancer (including specifically, aromatase inhibitors, anti-estrogens, chemotherapy, radiotherapy, and immunotherapy) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (until the toxicity resolves to either baseline or at least Grade 1) except for residual alopecia or peripheral neuropathy

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Exclusion Criteria

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
Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis visceral crisis is not the mere presence of visceral metastases but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of the disease
Have clinical evidence or history of central nervous system metastasis
Have received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, everolimus, or any CDK4/6 inhibitor
Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days prior to randomization of study drug for a nonmyelosuppressive or myelosuppressive agent, respectively
Have received recent (within 28 days prior to randomization) yellow fever vaccination
Have had major surgery within 14 days prior to randomization of study drug to allow for post-operative healing of the surgical wound and site(s)
Have a personal history within the last 12 months of any of the following conditions: syncope of cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest
Have inflammatory breast cancer or a history of any other cancer (except nonmelanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years
Have received an autologous or allogeneic stem-cell transplant
Have active bacterial or fungal infection, or detectable viral infection
Have initiated bisphosphonates or approved RANK ligand (RANK-L) targeted agents (for example, denosumab) <7 days prior to randomization

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Belgium	Not Recruiting	22 Jul 2014	3
Greece	Not Recruiting	22 Jul 2014	14
Italy	Not Recruiting	22 Jul 2014	2
Poland	Not Recruiting	22 Jul 2014	2
Spain	Not Recruiting	22 Jul 2014	3