SERENA-4: A Randomised, Multicentre, Double-Blind, Phase III Study of AZD9833 (an Oral SERD) Plus Palbociclib Versus Anastrozole Plus Palbociclib for the Treatment of Patients With Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer Who Have Not Received Any Systemic Treatment for Advanced Disease
Trial Snapshot
- Phase
- Phase 3
- Status
- Active, not recruiting
- Sponsor
- AstraZeneca
- Enrollment
- 1,370
- Locations
- 1
- Primary Endpoint
- Progression-free survival (PFS) assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST) version 1.1
Study Overview
Brief Summary
The study is intended to show superiority of AZD9833 in combination with palbociclib (a CDK4/6 inhibitor) versus anastrozole (an aromatase inhibitor) and palbociclib as the initial treatment of patients with hormone receptor-positive (ER-positive), human epidermal growth factor 2-negative (HER2-negative) advanced/metastatic breast cancer.
INFORMATION FOR TRIAL PARTICIPANTS
In this trial, the researchers will look at how well camizestrant with palbociclib works, compared with anastrozole with palbociclib, in participants with breast cancer that has either spread into other parts of the body at the time of diagnosis, or has come back after at least 2 years of standard endocrine treatment.
Participants in this trial will have breast cancer that has ER proteins but does not have overexpression of HER2 protein.
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 palbociclib versus anastrozole in combination with palbociclib for the treatment of patients with ER-positive breast cancer. The goal of the study is to demonstrate superiority of AZD9833 over anastrozole in the context of combination with palbociclib in first line setting.
INFORMATION FOR TRIAL PARTICIPANTS
Researchers are looking for a better way to treat breast cancer.
In people with cancer, some cells have grown out of control to form tumours.
The trial drugs palbociclib, camizestrant, and anastrozole are designed to work by blocking the cancer's ability to grow. Camizestrant is also called AZD9833. Palbociclib and anastrozole are already available as treatments for people with certain type of breast cancer.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 130 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
AZD9833 + palbociclib
The patients will receive AZD9833 (75 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (1 mg, PO, once daily)
Intervention: AZD9833 (Drug)
AZD9833 + palbociclib
The patients will receive AZD9833 (75 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (1 mg, PO, once daily)
Intervention: Anastrozole placebo (Drug)
AZD9833 + palbociclib
The patients will receive AZD9833 (75 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (1 mg, PO, once daily)
Intervention: Palbociclib (Drug)
Anastrozole + palbociclib
The patients will recieve Anastrozole (1 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily)
Intervention: Luteinizing hormone-releasing hormone (LHRH) agonist (Drug)
AZD9833 + palbociclib
The patients will receive AZD9833 (75 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (1 mg, PO, once daily)
Intervention: Luteinizing hormone-releasing hormone (LHRH) agonist (Drug)
Anastrozole + palbociclib
The patients will recieve Anastrozole (1 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily)
Intervention: Anastrozole (Drug)
Anastrozole + palbociclib
The patients will recieve Anastrozole (1 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily)
Intervention: AZD9833 placebo (Drug)
Anastrozole + palbociclib
The patients will recieve Anastrozole (1 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily)
Intervention: Palbociclib (Drug)
Outcomes
Primary Outcomes
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 progression per RECIST 1.1 as assessed by the investigator at local site or death due to any cause (up to 5 years)
PFS is defined as the time from randomization to objective disease progression (as assessed by RECIST) or death.
Secondary Outcomes
- Overall survival (OS)(From randomization until the date of death due to any cause (up to 8 years))
- Time to first subsequent anti-cancer therapy (TFST)(From randomization until the earlier of start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment, or death due to any cause (up to 5 years))
- Clinical benefit rate at 24 weeks (CBR24)(At least 23 weeks after randomisation)
- 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 (up to 5 years))
- Duration of response (DoR) assessed by the Investigator as defined by RECIST version 1.1(From the date of first documented response until date of documented progression per RECIST 1.1 as assessed by the investigator at local site or death due to any cause (up to 5 years))
- Time to chemotherapy (TTC)(From randomization until the earlier of the start date of chemotherapy or death due to any cause (up to 5 years))
- Time to second subsequent therapy (TSST)(From randomization until the earlier of start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause (up to 5 years))
- Change from baseline in EORTC QLQ-BR45 scale scores(From baseline to 24 weeks post progression (up to approximately 5 years))
- Second progression-free survival (PFS2)(From randomization to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death (up to 5 years))
- Plasma concentration of AZD9833 at specified timepoints(on Day 15)
- Change from baseline in EORTC QLQ-C30 scale scores(From baseline to 24 weeks post progression (up to approximately 5 years))