Breast Cancer, Early Breast Cancer
Conditions
Keywords
ER+, HER2-, breast cancer
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.
Interventions
DRUGCamizestrant
Camizestrant. Experimental. Administered orally
DRUGTamoxifen
Tamoxifen. Comparator. Administered orally
DRUGAnastrozole
Anastrozole. Comparator. Administered orally
DRUGLetrozole
Letrozole. Comparator. Administered orally
DRUGExemestane
Exemestane. Comparator. Administered orally
DRUGAbemaciclib
Abemaciclib adjuvant treatment Administered orally
Sponsors
Austrian Breast and Colorectal Cancer Study Group (ABCSG)
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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 ± abemaciclib
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
| 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. |
| 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) |
| 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) | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Croatia, Czechia, Estonia, France, Georgia, Germany, Greece, Hungary, India, Ireland, Israel, Italy, Japan, Malaysia, Mexico, New Zealand, Peru, Philippines, Poland, Portugal, Puerto Rico, Romania, Saudi Arabia, Serbia, South Africa, South Korea, Spain, Switzerland, Taiwan, Thailand, Turkey (Türkiye), United Arab Emirates, United Kingdom, United States
Contacts
Primary ContactAstraZeneca Clinical Study Information Center
Backup ContactAstraZeneca Breast Cancer Study Locator Service
Outcome results
None listed