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 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.
Detailed description
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.
Interventions
DRUGCamizestrant
Camizestrant. Experimental. Administered orally
DRUGTamoxifen
Tamoxifen. Comparator. Administered per local approved label
DRUGAnastrozole
Anastrozole. Comparator. Administered per local approved label
DRUGLetrozole
Letrozole. Comparator. Administered per local approved label
DRUGExemestane
Exemestane. Comparator. Administered per local approved label
Sponsors
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: Continue standard ET of investigator's choice (aromatase inhibitors \[AI; exemestane, letrozole, anastrozole\] or tamoxifen) * Arm B: Camizestrant
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 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 sex hormone therapy * 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 10 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 * Invasive contralateral breast cancer * Death attributable to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Invasive disease-free survival (IDFS) | Up to 10 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 * Invasive contralateral breast cancer * Second primary non-breast invasive cancer * Death attributable to any cause. |
| Distant relapse-free survival (DRFS) | Up to 10 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 10 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 5 years) | — |
| Absolute and percent change from baseline in Clinical Laboratory Parameters | Until 28 days after the final dose of study treatment (up to 5 years) | — |
| Absolute and percent change from baseline in Vital Sign Parameters | Until 28 days after the final dose of study treatment (up to 5 years) | — |
| Change from baseline of arthralgia as measured by the EORTC-IL-194 (European Organisation for Research and Treatment of Cancer) item 10. EORTC-IL-194 uses 0 - 4 scale (higher score is worse) | Until 28 days after the final dose of study treatment (up to 5 years) | — |
| Change from baseline of hot flush as measured by the EORTC-IL-194 item 4. EORTC-IL-194 uses 0 - 4 scale (higher score is worse) | Until 28 days after the final dose of study treatment (up to 5 years) | — |
| Change from baseline of vaginal dryness as measured by the EORTC-IL-194 item 15. EORTC-IL-194 uses 0 - 4 scale (higher score is worse) | Until 28 days after the final dose of study treatment (up to 5 years) | — |
| Proportion of patients experiencing each level of symptomatic AEs of arthralgia as measured by the EORTC-IL-194 item 10. EORTC-IL-194 uses 0 - 4 scale (higher score is worse) | Until 28 days after the final dose of study treatment (up to 5 years) | — |
| Proportion of patients experiencing each level of symptomatic AEs of hot flush as measured by the EORTC-IL-194 item 4. EORTC-IL-194 uses 0 - 4 scale (higher score is worse) | Until 28 days after the final dose of study treatment (up to 5 years) | — |
| Proportion of patients experiencing each level of symptomatic AEs of vaginal dryness as measured by the EORTC-IL-194 item 15. EORTC-IL-194 uses 0 - 4 scale (higher score is worse) | Until 28 days after the final dose of study treatment (up to 5 years) | — |
| Change from baseline and TTD (time to deterioration ) of health-related QoL (quality of life) as measured by the 2 global QoL items from the EORTC-QLQ-C30 items 11 and 12. EORTC-QLQ-C30 uses 0 - 4 scale (higher score is worse) | Until 28 days after the final dose of study treatment (up to 5 years) | — |
| Pharmacokinetics (PK) | Until 6 months from treatment start | • Plasma concentrations of camizestrant pre-dose (Ctrough)( trough concentration) |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czechia, France, Georgia, Germany, Greece, Hungary, India, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, Peru, Philippines, Poland, Portugal, Romania, Serbia, Singapore, South Africa, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States, Vietnam
Contacts
CONTACTAstraZeneca Clinical Study Information Center
CONTACTAstraZeneca Breast Cancer Study Locator Service
Outcome results
None listed