A Study of Camizestrant in ER+/HER2- Early Breast Cancer After at Least 2 Years of Standard Adjuvant Endocrine Therapy

Phase 3RecruitingNCT05774951

AstraZeneca4,300 enrolled

Overview

This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard endocrine therapy in patients with ER+/HER2 - early breast cancer with intermediate or high risk for disease recurrence who completed definitive locoregional therapy (with or without chemotherapy) and standard adjuvant endocrine therapy (ET) for at least 2 years and up to 5 years. The planned duration of treatment in either arm of the study is 60 months.

This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard endocrine therapy in patients with ER+/HER2 - early breast cancer who completed definitive locoregional therapy (with or without chemotherapy) and standard adjuvant endocrine therapy (ET) for at least 2 years and up to 5 years. The planned duration of treatment in either arm of the study is 60 months. The eligible patients must have intermediate or high risk of recurrence, as defined by specified clinical and biologic criteria. Prior use of CDK4/6 inhibitors is permitted. The primary endpoint of the study is Invasive breast cancer-free survival (IBCFS) and main secondary endpoints include Invasive disease-free survival (IDFS), Distant relapse-free survival (DRFS), Overall survival (OS), Safety and Clinical Outcome Assessments (COAs). Patients will be followed for 10 years from randomization of the last patient.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

4,300

Conditions

Breast Cancer, Early Breast Cancer

Eligibility

Sex: ALLMin age: 18 YearsMax age: 130 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Women and Men, ≥18 years at the time of screening (or per national guidelines) * Histologically confirmed ER+/HER2- early-stage resected invasive breast cancer with high or intermediate risk of recurrence, based on clinical-pathological risk features, as defined in the protocol. * Completed adequate (definitive) locoregional therapy (surgery with or without radiotherapy) for the primary breast tumour(s), with or without (neo)adjuvant chemotherapy * Completed at least 2 years but no more than 5 years (+3 months) of adjuvant ET (+/- CDK4/6 inhibitor) * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 * Adequate organ and marrow function Exclusion criteria: * Inoperable locally advanced or metastatic breast cancer * Pathological complete response following treatment with neoadjuvant therapy * History of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix or considered at very low risk of recurrence per investigator judgement) unless in complete remission with no therapy for a minimum of 5 years from the date of randomisation * Any evidence of severe or uncontrolled systemic diseases which, in the investigator's opinion precludes participation in the study or compliance * Known LVEF \<50% with heart failure NYHA Grade ≥2. * Mean resting QTcF interval \>480 ms at screening * Concurrent exogenous reproductive hormone therapy or non-topical hormonal therapy for non-cancer-related conditions * Any concurrent anti-cancer treatment not specified in the protocol with the exception of bisphosphonates (e.g. zoledronic acid) or RANKL inhibitors (eg, denosumab) * Previous treatment with camizestrant, investigational SERDs/investigational ER targeting agents, or fulvestrant * Currently pregnant (confirmed with positive serum pregnancy test) or breastfeeding * Patients with known hypersensitivity to active or inactive excipients of camizestrant or drugs with a similar chemical structure or class to camizestrant. In pre-/peri-menopausal female and male patients, known hypersensitivity or intolerance to LHRH agonists, that would preclude the patient from receiving any LHRH agonist

Outcomes

Primary Outcomes

Invasive breast cancer-free survival (IBCFS)

IBCFS is defined as time from randomisation until date of first occurrence of: * Invasive ipsilateral breast tumour recurrence (invasive IBTR) * Locoregional invasive breast cancer recurrence * Distant recurrence * Invasive contralateral breast cancer * Death attributable to any cause.

Time frame: Up to 10 years

Secondary Outcomes

Invasive disease-free survival (IDFS)

IDFS is defined as time from randomisation until date of first occurrence of one of the following events: * Invasive ipsilateral breast tumor recurrence (invasive IBTR) * Locoregional invasive breast cancer recurrence * Distant recurrence * Invasive contralateral breast cancer * Second primary non-breast invasive cancer * Death attributable to any cause.

Time frame: Up to 10 years

Distant relapse-free survival (DRFS)

DRFS is defined as time from randomisation until date of first distant recurrence or death from any cause, whichever occurs first.

Time frame: Up to 10 years

Overall survival (OS)

OS is defined as time from randomisation until death from any cause.

Time frame: Up to 10 years

Incidence and Severity of Adverse Events, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v5.0)