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

Sponsor

AstraZeneca (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05952557

Collaborator

(none)

5,500

Enrollment

Arms

163.9

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer, Early Breast Cancer	Drug: Camizestrant Drug: Tamoxifen Drug: Anastrozole Drug: Letrozole Drug: Exemestane Drug: Abemaciclib	Phase 3

Detailed Description

This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard 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 Design

Study Type:

Interventional

Anticipated Enrollment :

5500 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients will be randomised in a 1:1 ratio to one of the following arms: • Arm A: Standard ET of investigator's choice (aromatase inhibitors [AI; exemestane, letrozole, anastrozole] or tamoxifen) ± abemaciclib • Arm B: Camizestrant ± abemaciclibPatients will be randomised in a 1:1 ratio to one of the following arms: • Arm A: Standard ET of investigator's choice (aromatase inhibitors [AI; exemestane, letrozole, anastrozole] or tamoxifen) ± abemaciclib • Arm B: Camizestrant ± abemaciclib

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

CAMBRIA-2: A Phase III, Open-Label, Randomised Study to Assess the Efficacy and Safety of Camizestrant (AZD9833, a Next Generation, Oral Selective Estrogen Receptor Degrader) vs Standard Endocrine Therapy (Aromatase Inhibitor or Tamoxifen) as Adjuvant Treatment for Patients With ER+/HER2- Early Breast Cancer and an Intermediate-High or High Risk of Recurrence Who Have Completed Definitive Locoregional Treatment and Have No Evidence of Disease

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Jan 29, 2030

Anticipated Study Completion Date :

Apr 30, 2037

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm A: standard endocrine therapy of investigator´s choice ± abemaciclib standard endocrine therapy of investigator's choice (aromatase inhibitors [AI; exemestane, letrozole, anastrozole] or tamoxifen) ± abemaciclib	Drug: Tamoxifen Tamoxifen. Comparator. Administered orally Drug: Anastrozole Anastrozole. Comparator. Administered orally Drug: Letrozole Letrozole. Comparator. Administered orally Drug: Exemestane Exemestane. Comparator. Administered orally Drug: Abemaciclib Abemaciclib adjuvant treatment Administered orally
Experimental: Arm B: camizestrant ± abemaciclib camizestrant ± abemaciclib	Drug: Camizestrant Camizestrant. Experimental. Administered orally Other Names: AZD9833 Drug: Abemaciclib Abemaciclib adjuvant treatment Administered orally

Arm

Intervention/Treatment

Active Comparator: Arm A: standard endocrine therapy of investigator´s choice ± abemaciclib

standard endocrine therapy of investigator's choice (aromatase inhibitors [AI; exemestane, letrozole, anastrozole] or tamoxifen) ± abemaciclib

Drug: Tamoxifen

Tamoxifen. Comparator. Administered orally

Drug: Anastrozole

Anastrozole. Comparator. Administered orally

Drug: Letrozole

Letrozole. Comparator. Administered orally

Drug: Exemestane

Exemestane. Comparator. Administered orally

Drug: Abemaciclib

Abemaciclib adjuvant treatment Administered orally

Experimental: Arm B: camizestrant ± abemaciclib

camizestrant ± abemaciclib

Drug: Camizestrant

Camizestrant. Experimental. Administered orally

Other Names:

AZD9833

Drug: Abemaciclib

Abemaciclib adjuvant treatment Administered orally

Outcome Measures

Primary Outcome Measures

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 (invasive IBTR) Locoregional invasive breast cancer recurrence Distant recurrence Contralateral invasive breast cancer Death attributable to any cause.

Secondary Outcome Measures

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 (invasive IBTR) Locoregional invasive breast cancer recurrence Distant recurrence Contralateral invasive breast cancer Second primary non-breast invasive cancer Death attributable to any cause.
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.
Overall survival (OS) [Up to 14 years]
OS is defined as time from randomisation until death from any cause.
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)]
Change from baseline and time to deterioration of health-related quality of life as measured by the EORTC-QLQ-C30 items 11 and 12 [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 (Ctrough)( trough concentration)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 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.