Description:
The study is intended to show superiority of AZD9833 in combination with CDK4/6 inhibitor
(palbociclib or abemaciclib) versus aromatase inhibitors (anastrozole or letrozole) in
combination with CDK4/6 inhibitor in patients with hormone receptor-positive (HR-positive),
human epidermal growth factor receptor 2-negative (HER2-negative) metastatic breast cancer
with detectable ESR1 mutation
Title
- Brief Title: Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6)
- Official Title: 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 ESR1Mutation Without Disease Progression During 1L Treatment With Aromatase Inhibitor+ CDK4/6 Inhibitor- A ctDNA Guided Early Switch Study
Clinical Trial IDs
- ORG STUDY ID:
D8534C00001
- NCT ID:
NCT04964934
Conditions
- ER-Positive HER2-Negative Breast Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| AZD9833 | | AZD9833 + palbociclib or abemaciclib |
| AZD9833 Placebo | | Anastrozole or letrozole + palbociclib or abemaciclib |
| Anastrozole | | Anastrozole or letrozole + palbociclib or abemaciclib |
| Anastrozole placebo | | AZD9833 + palbociclib or abemaciclib |
| Letrozole | | Anastrozole or letrozole + palbociclib or abemaciclib |
| Letrozole placebo | | AZD9833 + palbociclib or abemaciclib |
| Palbociclib | | AZD9833 + palbociclib or abemaciclib |
| Abemaciclib | | AZD9833 + palbociclib or abemaciclib |
| Luteinizing hormone-releasing hormone (LHRH) agonist | | AZD9833 + palbociclib or abemaciclib |
Purpose
The study is intended to show superiority of AZD9833 in combination with CDK4/6 inhibitor
(palbociclib or abemaciclib) versus aromatase inhibitors (anastrozole or letrozole) in
combination with CDK4/6 inhibitor in patients with hormone receptor-positive (HR-positive),
human epidermal growth factor receptor 2-negative (HER2-negative) metastatic breast cancer
with detectable ESR1 mutation
Detailed Description
A Randomised, Multicentre, Double-Blind, Phase III study will evaluate the safety and
efficacy of AZD9833 (next generation oral SERD) in combination with CDK4/6 inhibitor
(palbociclib or abemaciclib) versus aromatase inhibitor (anastrozole or letrozole) in
combination with CDK4/6 inhibitor for the treatment of patients with HR-positive, HER2-
negative metastatic breast cancer with detectable ESR1 Mutation. The goal of the study is to
demonstrate superiority of AZD9833 over anastrozole or letrozole in the context of
combination with palbociclib or abemaciclib
Trial Arms
| Name | Type | Description | Interventions |
|---|
| AZD9833 + palbociclib or abemaciclib | Experimental | The patients will receive AZD9833 (75 mg, PO, once daily) + palbociclib (PO, once daily, 125, 100 or 75 mg for 21 consecutive days followed by 7 days off treatment) or abemaciclib (PO, twice daily, 150,100 or 50 mg) + anastrozole placebo ( PO, once daily) or letrozole placebo ( PO, once daily) | - AZD9833
- Anastrozole placebo
- Letrozole placebo
- Palbociclib
- Abemaciclib
- Luteinizing hormone-releasing hormone (LHRH) agonist
|
| Anastrozole or letrozole + palbociclib or abemaciclib | Active Comparator | The patients will recieve anastrozole (1 mg, PO, once daily) or letrozole (2.5 mg, PO, once daily) + palbociclib (PO, once daily, 125,100 or 75 mg for 21 consecutive days followed by 7 days off treatment) or abemaciclib (PO, twice daily, 150,100 or 50 mg) + AZD9833 placebo (PO, once daily) | - AZD9833 Placebo
- Anastrozole
- Letrozole
- Palbociclib
- Abemaciclib
- Luteinizing hormone-releasing hormone (LHRH) agonist
|
Eligibility Criteria
Inclusion Criteria:
- Proven diagnosis of adenocarcinoma of the breast with evidence of locoregionally
recurrent or metastatic disease not amenable to resection or radiation therapy with
curative intent.
- Documentation of histologically confirmed diagnosis of estrogen receptor positive
(ER+) /HER2- breast cancer based on local laboratory results.
- Currently on AI (letrozole or anastrozole) + CDK4/6 inhibitor (palbociclib or
abemaciclib) ± LHRH as the initial endocrine based treatment for advanced disease
- Eastern Cooperative Oncology Group performance status of 0 or 1.
- ESR1m positive detected by central testing of ctDNA
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory
tests, and other study procedures.
- Adequate organ and marrow function
Exclusion Criteria:
- Advanced, symptomatic, visceral spread, that are at risk of life-threatening
complications in the short term.
- Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or
leptomeningeal disease.
- Any evidence of severe or uncontrolled systemic diseases which, in the investigator's
opinion, makes it undesirable for the participant to participate in the study or that
would jeopardize compliance with the protocol.
- Patient with known or family history of severe heart disease
- Previous treatment with AZD9833, investigational SERDs or fulvestrant.
- Currently pregnant (confirmed with positive pregnancy test) or breastfeeding.
- Persistent non-haematological toxicities (CTCAE Grade > 2) caused by CDK4/6 inhibitor
and/or AI treatment.
| Maximum Eligible Age: | 130 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Progression-free survival (PFS) assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST version 1.1) |
| Time Frame: | From randomization until the earlier of the progression event or death (approximately 2 years) |
| Safety Issue: | |
| Description: | PFS is defined as the time from randomization to objective disease progression (as assessed by RECIST 1.1) or death. |
Secondary Outcome Measures
| Measure: | Progression-free survival 2 (PFS2) |
| Time Frame: | From randomization to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death (approximately 3.5 years) |
| Safety Issue: | |
| Description: | PFS2 is defined as the time from the randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death. |
| Measure: | Overall survival (OS) |
| Time Frame: | From randomization until the date of death due to any cause (approximately 5 years) |
| Safety Issue: | |
| Description: | The OS is defined as the time from randomization to death due to any cause. |
| Measure: | Chemotherapy free survival |
| Time Frame: | From randomization until the earlier of the start date of chemotherapy or death due to any cause (approximately 5 years) |
| Safety Issue: | |
| Description: | Time to chemotherapy is defined as the time from randomization until the earlier of the start date of chemotherapy or death due to any cause. |
| Measure: | Objective response rate (ORR) assessed by the Investigator as defined by RECIST version 1.1 |
| Time Frame: | From randomization until a response or in the absence of a response from randomization up until progression, or the last evaluable assessment in the absence of progression (approximately 5 years) |
| Safety Issue: | |
| Description: | ORR is defined as the proportion of patients who have a complete response (CR) or partial response (PR), as determined by the investigator at local site per RECIST 1.1. |
| Measure: | Clinical benefit rate at 24 weeks (CBR24) |
| Time Frame: | At least 23 weeks after randomisation for each patient (1 week window for RECIST assessment) |
| Safety Issue: | |
| Description: | CBR at 24 weeks is defined as the percentage of participants who have a complete response (CR) or partial response or who have stable disease (SD) per RECIST 1.1 as assessed by the investigator at local site for At least 23 weeks after randomisation for each patient to allow for an early assessment within the assessment window (1 week window for RECIST assessment) |
| Measure: | Change from baseline in EORTC QLQ-C30 scale scores |
| Time Frame: | From baseline until second progression (approximately 5 years) |
| Safety Issue: | |
| Description: | Change from baseline in scales scores of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Scale scores range from 0-100. For functioning and global health status/ QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden. |
| Measure: | Change from baseline in EORTC QLQ-BR23 scale scores |
| Time Frame: | From baseline until second progression (approximately 5 years) |
| Safety Issue: | |
| Description: | Change from baseline in scales scores of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ-BR23). Scale scores range from 0-100. For functioning scales, higher scores indicate better functioning. For symptom scales, higher scores indicate greater symptom burden. |
| Measure: | Plasma concentration of AZD9833 at specified timepoints |
| Time Frame: | on Day 15 for each patient |
| Safety Issue: | |
| Description: | To assess the steady state PK of AZD9833 in combination with palbociclib or abemaciclib in all participants who receive at least one dose of AZD9833 per the protocol, for whom there are at least one reportable PK concentration. |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | AstraZeneca |
Trial Keywords
- Metastatic
- Breast Neoplasms
- Neoplasms by Site
- Neoplasms
- Breast Diseases
- Physiological Effects of Drugs
- Randomised
- Multicentre
- Double-Blind
- Phase III
- AZD9833
- Next Generation Oral SERD
- Anastrozole
- Letrozole
- Palbociclib
- Abemaciclib
- Antagonists
- Antineoplastic Agents
- Estrogen Receptor Antagonists
- Hormone Antagonists
- camizestrant
- ESR1m
- Switch Treatment
- Endocrine Therapy
- Endocrine Resistance
Last Updated
August 20, 2021
