*SERENA-6: A Phase III Study to Assess Switching to AZD9833 + CDK4/6 Inhibitor
Research type
Research Study
Full title
SERENA-6: A Phase III, Double-blind, Randomised Study to Assess Switching to AZD9833 (a Next Generation, Oral SERD) + CDK4/6 Inhibitor (Palbociclib or Abemaciclib) vs Continuing Aromatase Inhibitor (Letrozole or Anastrozole) + CDK4/6 Inhibitor in HR+/HER2- MBC Patients with Detectable ESR1 Mutation Without Disease Progression During 1L Treatment with Aromatase Inhibitor + CDK4/6 Inhibitor
IRAS ID
1003884
Contact name
Adilah Hussain
Contact email
Sponsor organisation
AstraZeneca AB
Eudract number
2021-000546-17
Clinicaltrials.gov Identifier
Research summary
For this type of metastatic breast cancer (HR+/HER2-), current treatment guidelines recommend a combination of two types of therapy as the first line of treatment: an “aromatase inhibitor” (“AI” – drugs like anastrozole or letrozole) with a “CDK4/6 inhibitor” (“CDK4/6i”, drugs like palbociclib or abemaciclib). Most patients eventually have cancer progression on this treatment. Subsequent treatments can have limited efficacy, with side-effects that are hard to tolerate.
Mutations on the oestrogen receptor (known as “ESR1m”) are associated with resistance to treatment, and . evidence indicates that these mutations are also associated with poor long term outcomes for patients – i.e. their disease may get worse sooner, or their overall survival might be shorter.
This study aims to use new technology to target resistance mechanisms early - before the disease progresses - by switching the AI part of the treatment to AZD9833 . This approach has the potential to maximise time on first-line treatment, by delaying the time to treatment resistance, and to disease progression.
After signing initial consent, blood samples will be taken for ESR1m status test every 8 to 12 weeks. If, at any point, ESR1m is detected as positive and there is no evidence of disease progression, the patient will be consented to undergo further assessments to check eligibility for the Treatment Phase. Patients who enter the Treatment Phase will be randomised in a 1:1 ratio to receive AZD9833 + CDK4/6i or to continue on their existing AI + CDK4/6i. Patients will be followed up during regular treatment cycles until progression or other treatment discontinuation criteria are met. Survival follow-up will then occur until death, withdrawal of consent or end of study (Jun 2026). The duration of the study for each patient is variable and depends on the response to study treatment.
REC name
South West - Central Bristol Research Ethics Committee
REC reference
22/SW/0118
Date of REC Opinion
15 Sep 2021
REC opinion
Further Information Favourable Opinion