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.
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
Primary outcome:
1. Invasive breast cancer-free survival (IBCFS) (Time Frame - 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 outcome:
1. Invasive disease-free survival (IDFS) (Time Frame - 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.
2. Distant relapse-free survival (DRFS) (Time Frame - 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.
3. Overall survival (OS) (Time Frame - Up to 10 years):
OS is defined as time from randomisation until death from any cause.
4. 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) (Time Frame - Until 28 days after the final dose of study treatment (up to 5 years))
5. Absolute and percent change from baseline in Clinical Laboratory Parameters (Time Frame - Until 28 days after the final dose of study treatment (up to 5 years))
6. Absolute and percent change from baseline in Vital Sign Parameters (Time Frame - Until 28 days after the final dose of study treatment (up to 5 years))
7. Number of participants with abnormal physical examinations (Time Frame - Until 28 days after the final dose of study treatment (up to 5 years))
8. 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) (Time Frame - Until 28 days after the final dose of study treatment (up to 5 years))
9. 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) (Time Frame - Until 28 days after the final dose of study treatment (up to 5 years))
10. 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) (Time Frame - Until 28 days after the final dose of study treatment (up to 5 years))
11. 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) (Time Frame - Until 28 days after the final dose of study treatment (up to 5 years))
12. 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) (Time Frame - Until 28 days after the final dose of study treatment (up to 5 years))
13. 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) (Time Frame - Until 28 days after the final dose of study treatment (up to 5 years))
14. 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) (Time Frame - Until 28 days after the final dose of study treatment (up to 5 years))
15. Pharmacokinetics (PK) (Time Frame - Until 6 months from treatment start):
• Plasma concentrations of camizestrant pre-dose (Ctrough)( trough concentration)
- Active Comparator: Arm A: standard endocrine therapy of investigator´s choice
Continue standard endocrine therapy of investigator's choice (aromatase inhibitors [AI; exemestane, letrozole, anastrozole] or tamoxifen) - Experimental: Arm B: camizestrant
Camizestrant
- Camizestrant (AZD9833):
Camizestrant. Experimental. Administered orally - Tamoxifen:
Tamoxifen. Comparator. Administered per local approved label - Anastrozole:
Anastrozole. Comparator. Administered per local approved label - Letrozole:
Letrozole. Comparator. Administered per local approved label - Exemestane:
Exemestane. Comparator. Administered per local approved label
Quelle: ClinicalTrials.gov
