Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6)
- Conditions
- ER-Positive HER2-Negative Breast Cancer
- Interventions
- Drug: AZD9833 PlaceboDrug: Luteinizing hormone-releasing hormone (LHRH) agonist
- Registration Number
- NCT04964934
- Lead Sponsor
- AstraZeneca
- Brief Summary
The study is intended to show superiority of AZD9833 in combination with CDK4/6 inhibitor (palbociclib, abemaciclib or ribociclib) 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
Breast cancer is the most common type of cancer among women. In people with breast cancer, the body is not able to control the growth of some cells. These extra cells can form tumors in the breast. When tumor cells move to different parts of the body this is called advanced cancer. Researchers are looking for better ways to treat advanced breast cancer.
This trial will look at six drugs: palbociclib, abemaciclib, ribociclib, letrozole, anastrozole, and AZD9833. AZD9833 is the trial drug, and is the only drug not yet approved for use. Palbociclib, abemaciclib and ribociclib work in the same way and are a type of cancer drug called a CDK4/6 inhibitor. Letrozole and anastrozole work in the same way and are both a type of cancer drug called an aromatase inhibitor (AI). CDK4/6 inhibitors and AIs work together to block the tumor's ability to grow. These drugs have been approved for combined use in people with advanced breast cancer that is HR-positive and HER2-negative. But if people get mutations in the ESR1 gene, it can make the AI and CDK4/6 inhibitor treatment work less well.
The trial drug, AZD9833, is designed to work with a CDK4/6 inhibitor in the same way that an AI does. Researchers think that AZD9833 might work better with a CDK4/6 inhibitor than an AI does in people who get mutations in their ESR1 gene.
Participants in this trial will have already been receiving one of the following combinations of a CDK4/6 inhibitor and an AI:
* palbociclib + anastrozole
* palbociclib + letrozole
* abemaciclib + anastrozole
* abemaciclib + letrozole
* ribociclib + anastrozole
* ribociclib + letrozole
During the trial, participants will remain on the same CDK4/6 inhibitor that they were taking before the trial.
In this trial, the researchers want to find out how well switching a participant with an ESR1 gene mutation from an AI (letrozole or anastrozole) to AZD9833 works in the treatment of advanced breast cancer that is HR-positive and HER2-negative.
The researchers will look at which trial treatment helps the participants live longer with the cancer before it gets worse.
The researchers also want to know more about how safe AZD9833 is.
The trial participants will be split into 2 groups:
* Participants in Group A will receive AZD9833, a CDK4/6 inhibitor, and a placebo
* Participants in Group B will receive an AI, a CDK4/6 inhibitor, and a placebo
A placebo looks like a treatment but does not have any medicine in it.
A computer program will be used to randomly choose the treatments each participant gets. This helps make sure the groups are chosen fairly. Researchers do this so that comparing the results of each treatment will be as accurate as possible.
The participants will take their trial treatments over 28-day cycles, with a placebo and either AZD9833 or an AI taken once daily by mouth for all 28 days. If the participant is taking abemaciclib, they will take it twice daily by mouth for all 28 days. If the participant is taking palbociclib or ribociclib, they will take it once daily by mouth for 21 days and then stop taking it for the final 7 days of the cycle. The participant will then repeat the 28-day cycle receiving the trial treatment in the same way for as long as they are in the trial.
Participants will visit their trial site regularly throughout the trial. At these visits, the trial doctors will check the health of the participants. They will also take blood samples and do scans of the participants' tumors.
Participants will take their trial treatment until their cancer gets worse or they decide to leave the trial.
\*Palbociclib and Abemacliclib cohorts are currently ongoing. Ribociclib cohort will be open pending on availability of the data.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 315
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AZD9833 + palbociclib, abemaciclib or ribociclib AZD9833 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), abemaciclib (PO, twice daily, 150,100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (PO, once daily) or letrozole placebo (PO, once daily) Anastrozole or letrozole + palbociclib, abemaciclib or ribociclib AZD9833 Placebo 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), abemaciclib (PO, twice daily, 150, 100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily) AZD9833 + palbociclib, abemaciclib or ribociclib Anastrozole placebo 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), abemaciclib (PO, twice daily, 150,100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (PO, once daily) or letrozole placebo (PO, once daily) AZD9833 + palbociclib, abemaciclib or ribociclib Letrozole placebo 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), abemaciclib (PO, twice daily, 150,100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (PO, once daily) or letrozole placebo (PO, once daily) AZD9833 + palbociclib, abemaciclib or ribociclib Luteinizing hormone-releasing hormone (LHRH) agonist 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), abemaciclib (PO, twice daily, 150,100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (PO, once daily) or letrozole placebo (PO, once daily) AZD9833 + palbociclib, abemaciclib or ribociclib Abemaciclib 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), abemaciclib (PO, twice daily, 150,100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (PO, once daily) or letrozole placebo (PO, once daily) Anastrozole or letrozole + palbociclib, abemaciclib or ribociclib Letrozole 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), abemaciclib (PO, twice daily, 150, 100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily) Anastrozole or letrozole + palbociclib, abemaciclib or ribociclib Luteinizing hormone-releasing hormone (LHRH) agonist 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), abemaciclib (PO, twice daily, 150, 100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily) AZD9833 + palbociclib, abemaciclib or ribociclib Palbociclib 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), abemaciclib (PO, twice daily, 150,100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (PO, once daily) or letrozole placebo (PO, once daily) AZD9833 + palbociclib, abemaciclib or ribociclib Ribociclib 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), abemaciclib (PO, twice daily, 150,100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (PO, once daily) or letrozole placebo (PO, once daily) Anastrozole or letrozole + palbociclib, abemaciclib or ribociclib Anastrozole 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), abemaciclib (PO, twice daily, 150, 100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily) Anastrozole or letrozole + palbociclib, abemaciclib or ribociclib Abemaciclib 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), abemaciclib (PO, twice daily, 150, 100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily) Anastrozole or letrozole + palbociclib, abemaciclib or ribociclib Palbociclib 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), abemaciclib (PO, twice daily, 150, 100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily) Anastrozole or letrozole + palbociclib, abemaciclib or ribociclib Ribociclib 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), abemaciclib (PO, twice daily, 150, 100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily)
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST version 1.1) From randomization until the earlier of the progression event or death (approximately 2 years) PFS is defined as the time from randomization to objective disease progression (as assessed by RECIST 1.1) or death.
- Secondary Outcome Measures
Name Time Method Progression-free survival 2 (PFS2) From randomization to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death (approximately 3.5 years) 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.
Overall survival (OS) From randomization until the date of death due to any cause (approximately 5 years) The OS is defined as the time from randomization to death due to any cause.
Chemotherapy free survival From randomization until the earlier of the start date of chemotherapy or death due to any cause (approximately 5 years) 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.
Objective response rate (ORR) assessed by the Investigator as defined by RECIST version 1.1 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) 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.
Change from baseline in EORTC QLQ-C30 scale scores From baseline until second progression (approximately 5 years) 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.
Clinical benefit rate at 24 weeks (CBR24) At least 23 weeks after randomisation for each patient (1 week window for RECIST assessment) 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)
Change from baseline in EORTC QLQ-BR23 scale scores From baseline until second progression (approximately 5 years) 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.
Plasma concentration of AZD9833 at specified timepoints on Day 15 for each patient 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.
Trial Locations
- Locations (1)
Research Site
🇬🇧Taunton, United Kingdom