Phase III Study on AZD9833 and CDK4/6 Inhibitor for Advanced Breast Cancer with ESR1 Mutation (SERENA-6)

Sponsor: AstraZeneca

Sponsor score: 40
Inactive

ClinicalTrials ID:NCT04964934

Provider View

This clinical trial is testing a new drug, AZD9833, combined with a CDK4/6 inhibitor, to see if it works better than current treatments for patients with advanced breast cancer that has a specific gene mutation (ESR1).

Patient Parameters

Program Overview

The study aims to find out if AZD9833, when used with a CDK4/6 inhibitor, is more effective than current treatments for patients with advanced breast cancer that is hormone receptor-positive (HR-positive) and HER2-negative, and has a detectable ESR1 mutation. Researchers want to see if this new combination can help patients live longer without their cancer getting worse and to learn more about the safety of AZD9833.

Description

Breast cancer is the most common cancer in women, and it can spread to other parts of the body, becoming advanced cancer. This trial is exploring better treatment options for advanced breast cancer.

The trial involves six drugs: palbociclib, abemaciclib, ribociclib, letrozole, anastrozole, and AZD9833. AZD9833 is the new drug being tested. Palbociclib, abemaciclib, and ribociclib are CDK4/6 inhibitors, while letrozole and anastrozole are aromatase inhibitors (AIs). These drugs are used together to stop cancer growth in HR-positive, HER2-negative breast cancer. However, a mutation in the ESR1 gene can make these treatments less effective.

AZD9833 is designed to work with a CDK4/6 inhibitor like an AI does, and researchers believe it might be more effective for patients with the ESR1 mutation.

Participants in this trial will have already been taking a combination of a CDK4/6 inhibitor and an AI. During the trial, they will continue with the same CDK4/6 inhibitor.

The trial will compare the effectiveness of switching from an AI to AZD9833 in patients with the ESR1 mutation. Researchers will assess which treatment helps patients live longer before their cancer worsens and will also evaluate the safety of AZD9833.

Participants will be divided into two groups:

  • Group A will receive AZD9833, a CDK4/6 inhibitor, and a placebo.
  • Group B will receive an AI, a CDK4/6 inhibitor, and a placebo.

A placebo is a substance that looks like the treatment but has no active medicine. A computer will randomly assign participants to each group to ensure fair comparison.

Participants will take their trial treatments in 28-day cycles, with either AZD9833 or an AI taken daily. If taking abemaciclib, it will be taken twice daily. Palbociclib or ribociclib will be taken for 21 days, followed by a 7-day break. This cycle will repeat as long as participants are in the trial.

Regular visits to the trial site will include health checks, blood tests, and tumor scans. Participants will continue the trial treatment until their cancer progresses or they choose to leave the trial.

*Note: Palbociclib and Abemaciclib cohorts are ongoing. Ribociclib cohort will open based on data availability.

Eligibility Criteria

Inclusion Criteria

  • Have advanced breast cancer that cannot be treated with surgery or radiation.
  • Have an ESR1 mutation in their cancer.
  • Have HR-positive and HER2-negative breast cancer.
  • Currently treated with a CDK4/6 inhibitor and an AI for at least 6 months.
  • Cancer has not worsened after taking an AI and CDK4/6 inhibitor.
  • Able to perform daily activities.
  • At least 18 years old.

Full list:

  • Proven diagnosis of advanced breast cancer not treatable with surgery or radiation.
  • Confirmed ER+/HER2- breast cancer.
  • Currently on AI (letrozole or anastrozole) + CDK4/6 inhibitor (palbociclib, abemaciclib, or ribociclib) ± LHRH.
  • ECOG performance status of 0 or 1.
  • ESR1 mutation detected by central testing.
  • Willing and able to comply with study requirements.
  • Adequate organ and marrow function.

Exclusion Criteria

  • Had certain types of tumors in the past that may return.
  • Currently taking other treatments that could interfere with the trial.
  • Have major health problems, infections, or recent surgeries that could complicate participation.

Full list:

  • Advanced, symptomatic cancer spread at risk of life-threatening complications.
  • Uncontrolled or symptomatic CNS metastases or related conditions.
  • Severe or uncontrolled systemic diseases.
  • Known or family history of severe heart disease.
  • Previous treatment with AZD9833 or similar drugs.
  • Currently pregnant or breastfeeding.
  • Persistent severe side effects from CDK4/6 inhibitor and/or AI treatment.

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