An Adjuvant Endocrine-based Therapy Study of Camizestrant (AZD9833) in ER+/HER2- Early Breast Cancer (CAMBRIA-2)

Phase 3

Recruiting

• Conditions: Breast Cancer, Early Breast Cancer
• Interventions: Drug: Tamoxifen; Drug: Camizestrant; Drug: Anastrozole; Drug: Abemaciclib; Drug: Letrozole; Drug: Exemestane

• Registration Number: NCT05952557
• Lead Sponsor: AstraZeneca

Brief Summary

This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard adjuvant endocrine therapy for patients with ER+/HER2- early breast cancer with intermediate-high or high risk for disease recurrence who completed definitive locoregional therapy (with or without chemotherapy). The planned duration of treatment in either arm within the study will be 7 years.

Detailed Description

This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard adjuvant endocrine therapy for patients with ER+/HER2- early breast cancer with intermediate-high or high risk for disease recurrence who completed definitive locoregional therapy (with or without chemotherapy). The planned duration of treatment in either arm of the study is 7 years. Eligible patients must have intermediate-high or high risk of recurrence as defined by specified clinical and biologic criteria. Concurrent use of abemaciclib is permitted in both arms. 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 Timeline

• Study First Submitted: 2023-05-17
• Study First Submitted QC: 2023-07-11
• Study First Posted: 2023-07-19
• Study Start: 2023-10-05
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-20
• Last Update Posted: 2025-05-21
• Primary Completion: 2030-03-04
• Study Completion: 2037-05-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 5500

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 absence of any evidence of metastatic disease 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.
• Patients must be randomised within 12 months of definitive breast surgery.
• Patients may have received up to 12 weeks of endocrine therapy prior to randomisation.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
• Adequate organ and bone 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 a 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: standard endocrine therapy of investigator´s choice ± abemaciclib	Anastrozole	standard endocrine therapy of investigator's choice (aromatase inhibitors \[AI; exemestane, letrozole, anastrozole\] or tamoxifen) ± abemaciclib
Arm A: standard endocrine therapy of investigator´s choice ± abemaciclib	Exemestane	standard endocrine therapy of investigator's choice (aromatase inhibitors \[AI; exemestane, letrozole, anastrozole\] or tamoxifen) ± abemaciclib
Arm A: standard endocrine therapy of investigator´s choice ± abemaciclib	Letrozole	standard endocrine therapy of investigator's choice (aromatase inhibitors \[AI; exemestane, letrozole, anastrozole\] or tamoxifen) ± abemaciclib
Arm A: standard endocrine therapy of investigator´s choice ± abemaciclib	Tamoxifen	standard endocrine therapy of investigator's choice (aromatase inhibitors \[AI; exemestane, letrozole, anastrozole\] or tamoxifen) ± abemaciclib
Arm B: camizestrant ± abemaciclib	Camizestrant	camizestrant ± abemaciclib
Arm B: camizestrant ± abemaciclib	Abemaciclib	camizestrant ± abemaciclib
Arm A: standard endocrine therapy of investigator´s choice ± abemaciclib	Abemaciclib	standard endocrine therapy of investigator's choice (aromatase inhibitors \[AI; exemestane, letrozole, anastrozole\] or tamoxifen) ± abemaciclib

Primary Outcome Measures

Name	Time	Method
Invasive breast cancer-free survival (IBCFS)	Up to 14 years	IBCFS is defined as time from randomisation until date of first occurrence of: * Invasive ipsilateral breast tumour recurrence; * Locoregional invasive breast cancer recurrence; * Distant recurrence; * Contralateral invasive breast cancer; * Death attributable to any cause.

Secondary Outcome Measures

Name	Time	Method
Distant relapse-free survival (DRFS)	Up to 14 years	DRFS is defined as time from randomisation until date of first distant recurrence or death from any cause, whichever occurs first.
Change from baseline and time to deterioration of health-related quality of life as measured by the 2 global QoL items from the EORTC IL-311	Until 28 days after the final dose of study treatment (up to 7 years)
Pharmacokinetics (PK)	Until 6 months from treatment start	Plasma concentrations of camizestrant pre-dose (trough concentration)
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)	Until 28 days after the final dose of study treatment (up to 7 years)
Proportion of time on study treatment with high side-effect burden as measured by the PGI-TT.	Until 28 days after the final dose of study treatment (up to 7 years)
Invasive disease-free survival (IDFS)	Up to 14 years	IDFS is defined as time from randomisation until date of first occurrence of one of the following events: * Invasive ipsilateral breast tumor recurrence; * Locoregional invasive breast cancer recurrence; * Distant recurrence; * Contralateral invasive breast cancer; * Second primary non-breast invasive cancer; * Death attributable to any cause.
Overall survival (OS)	Up to 14 years	OS is defined as time from randomisation until death from any cause.

Trial Locations

Locations (1)

Research Site; 🇬🇧 Whitchurch, United Kingdom