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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase III, Open-Label, Randomised Study to Assess the Efficacy and Safety of Extended Therapy With Camizestrant Versus Standard Endocrine Therapy (Aromatase Inhibitor or Tamoxifen) in Patients With ER+/HER2- Early Breast Cancer

Conditions
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Breast Cancer, Early Breast Cancer

Intervention / Treatment
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* Drug: Camizestrant
* Drug: Tamoxifen
* Drug: Anastrozole
* Drug: Letrozole
* Drug: Exemestane


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A: standard endocrine therapy of investigator´s choice<br>Continue standard endocrine therapy of investigator's choice (aromatase inhibitors [AI; exemestane, letrozole, anastrozole] or tamoxifen) | Drug: Tamoxifen<br>* Tamoxifen. Comparator. Administered per local approved label<br>Drug: Anastrozole<br>* Anastrozole. Comparator. Administered per local approved label<br>Drug: Letrozole<br>* Letrozole. Comparator. Administered per local approved label<br>Drug: Exemestane<br>* Exemestane. Comparator. Administered per local approved label<br>|
| Experimental: Arm B: camizestrant<br>Camizestrant | Drug: Camizestrant<br>* Camizestrant. Experimental. Administered orally<br>* Other names: AZD9833;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | Up to 10 years | 
| Overall survival (OS) | OS is defined as time from randomisation until death from any cause. | 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) |  | 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) | 
| Number of participants with abnormal physical examinations |  | 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) | • Plasma concentrations of camizestrant pre-dose (Ctrough)( trough concentration) | Until 6 months from treatment start | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ER+, HER2-, breast cancer