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.
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.
Primary outcome:
1. Invasive breast cancer-free survival (IBCFS) (Time Frame - 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 outcome:
1. Invasive disease-free survival (IDFS) (Time Frame - 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.
2. Distant relapse-free survival (DRFS) (Time Frame - 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.
3. Overall survival (OS) (Time Frame - Up to 14 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 7 years))
5. Proportion of time on study treatment with high side-effect burden as measured by the PGI-TT. (Time Frame - Until 28 days after the final dose of study treatment (up to 7 years))
6. 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 (Time Frame - Until 28 days after the final dose of study treatment (up to 7 years))
7. Pharmacokinetics (PK) (Time Frame - Until 6 months from treatment start):
Plasma concentrations of camizestrant pre-dose (trough concentration)
- 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 - Experimental: Arm B: camizestrant ± abemaciclib
camizestrant ± abemaciclib
- Camizestrant (AZD9833):
Camizestrant. Experimental. Administered orally - Tamoxifen:
Tamoxifen. Comparator. Administered orally - Anastrozole:
Anastrozole. Comparator. Administered orally - Letrozole:
Letrozole. Comparator. Administered orally - Exemestane:
Exemestane. Comparator. Administered orally - Abemaciclib:
Abemaciclib adjuvant treatment Administered orally
Quelle: ClinicalTrials.gov
