Title
Cambria-2: A Phase III, Open-Label, Randomised Study to Assess the Efficacy and Safety Of Camizestrant (AZD9833, a Next Generation, Oral Selective Estrogen Receptor Degrader) VS Standard Endocrine Therapy (Aromatase Inhibitor or Tamoxifen) As Adjuvant Treatment For Patients With ER+/HER2- Early Breast Cancer and an Intermediate-High or High Risk Of Recurrence Who Have Completed Definitive Locoregional Treatment and Have No Evidence Of Disease

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 within the study will be 7 years.

Objective
Primary Objective:
1. To demonstrate superiority of camizestrant ± abemaciclib as compared to standard ET ± abemaciclib by assessment of invasive breast cancer-free survival (IBCFS).

Secondary Objective:
1. To demonstrate superiority of camizestrant ± abemaciclib as compared to standard ET ± abemaciclib by assessment of invasive disease-free survival (IDFS).
2. To demonstrate superiority of camizestrant ± abemaciclib as compared to standard ET ± abemaciclib by assessment of distant relapse-free survival (DRFS).
3. To demonstrate superiority of camizestrant ± abemaciclib as compared to standard ET ± abemaciclib by assessment of overall survival (OS).
4. To demonstrate superior tolerability of camizestrant ± abemaciclib as compared to standard ET ± abemaciclib by assessment of the proportion of time on study treatment with high side-effect burden.
5. To assess patient-reported treatment-associated symptoms of arthralgia, hot flush, and vaginal dryness of camizestrant ± abemaciclib as compared to standard ET ± abemaciclib.
6. To assess patient-reported health-related QoL in patients treated with camizestrant ± abemaciclib as compared to standard ET ± abemaciclib.
7. To assess the steady-state PK of camizestrant in patients who received at least 1 dose of camizestrant per the protocol, for whom there is at least 1 reportable PK concentration.

Treatment 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).

Key Eligibility 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
Adequate organ and bone marrow function

Applicable Disease Sites
Breast

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital