A randomized, double-blind phase 3 study of AZD9833 plus Palbociclib compared to Anastrozole plus Palbociclib in patients with estrogen receptor-positive HER2-negative breast cancer who have not received systemic treatment for advanced disease (SERENA-4)
Summary description of the study
This study is being conducted at approximately 110 hospitals in around 20 countries. In Switzerland, 3 hospitals are involved. The study aims to determine the efficacy and safety of an investigational drug AZ9833 called Camizestrant in patients with estrogen receptor-positive/HER-negative breast cancer. This trial is intended to find out whether the investigational substance Camizestrant (AZD9833) plus Palbociclib is better than Anastrozole plus Palbociclib. Aromatase inhibitors (Anastrozole) are considered the standard therapy for the above-mentioned breast cancer. Unfortunately, the disease often changes during treatment, and thus the therapy becomes less effective over time. Patients develop what is called resistance. Resistant patients are currently treated with a drug called Fulvestrant. It belongs to the same class of drugs as Camizestrant. Fulvestrant is administered once a month as an injection into a muscle. Camizestrant, however, is taken as a tablet daily by mouth. It is hoped that the effect of Camizestrant will be better than that of Fulvestrant because it remains in the body at a higher dose for a longer period. Thus, a breakthrough or at least a delay in resistance to treatment is expected. It is planned that 1680 patients will be pre-screened worldwide to randomize 1342 participants into study treatment in one of two groups (in Switzerland 3-5 patients). Patients will be randomly assigned in a 1:1 ratio to one of two treatment groups. Treatment in both groups will continue until disease progression, unacceptable side effects occur, or if the investigators have other reasons to end study participation. After that, follow-up will begin every 12 weeks until death, study end, or withdrawal of consent.
(BASEC)
Intervention under investigation
Patients will be randomly assigned in a 1:1 ratio to one of the following two treatment groups:
Group A: Investigational substance Camizestrant (AZD9833) + Palbociclib
Group B: Anastrozole (Aromatase inhibitor) + Palbociclib
Medications in this study are taken orally (by mouth) as a tablet.
(BASEC)
Disease under investigation
Estrogen receptor-positive, HER-negative, advanced breast cancer that has not been treated systemically to date
(BASEC)
The main inclusion criteria are: 1. Participants must have a certain type of breast cancer that is estrogen receptor-positive/HER-negative, locally advanced and not suitable for surgical removal or radiation therapy with curative intent. 2. De novo stage 4 disease OR 3. Recurrence of early-stage breast cancer after adjuvant endocrine standard therapy 4. Measurable disease that can be determined by CT/MRI 5. Written informed consent provided. (BASEC)
Exclusion criteria
The main exclusion criteria: 1. Prior treatment with systemic cancer therapies for locoregional recurrence or metastasis of an estrogen receptor-positive breast cancer 2. Patients with advanced spread to internal organs 3. Patients with a medical or genetically induced heart disease. (BASEC)
Trial sites
Basel, Bern, Zurich
(BASEC)
Sponsor
AstraZeneca GmbH
(BASEC)
Contact
Contact Person Switzerland
Silviya Cantatore
+41 79 158 23 91
silviya.cantatore@clutterastrazeneca.comAstraZeneca AG
(BASEC)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee northwest/central Switzerland EKNZ
(BASEC)
Date of authorisation
20.07.2022
(BASEC)
ICTRP Trial ID
NCT04711252 (ICTRP)
Official title (approved by ethics committee)
Eine randomisierte, doppelblinde Phase-3-Studie zu AZD9833 plus Palbociclib im Vergleich zu Anastrozol plus Palbociclib bei Patienten mit Östrogenrezeptor-positivem HER2-negativem Mammakarzinom, die bisher keine systemische Behandlung der fortgeschrittenen Erkrankung erhalten haben (SERENA-4) (BASEC)
Academic title
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 (ICTRP)
Public title
A Comparative Study of AZD9833 Plus Palbociclib Versus Anastrozole Plus Palbociclib in Patients With ER-Positive HER2 Negative Breast Cancer Who Have Not Received Any Systemic Treatment for Advanced Disease (ICTRP)
Disease under investigation
ER-Positive HER2-Negative Breast Cancer (ICTRP)
Intervention under investigation
Drug: AZD9833Drug: AnastrozoleDrug: Anastrozole placeboDrug: AZD9833 placeboDrug: PalbociclibDrug: Luteinizing hormone-releasing hormone (LHRH) agonist (ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator). (ICTRP)
Inclusion/Exclusion criteria
INCLUSION CRITERIA
Full list of inclusion criteria
- Pre-/peri-menopausal women or men can be enrolled if amenable to be treated with
concomitant, approved LHRH agonists for the duration of the study treatment.
- De novo Stage 4 disease, or recurrence from early stage disease after at least 24
months of standard adjuvant endocrine therapy. Note that at least 12 months must
have elapsed since the patient's last dose of adjuvant AI therapy without disease
progression on treatment. Note that a 2-week washout period is required after the
last dose of tamoxifen prior to randomisation.
- Histologically or cytologically documented diagnosis of ER+, HER2-negative breast
cancer based on local laboratory results.
- Previously untreated with any systemic anti-cancer therapy for their locoregionally
recurrent or metastatic ER+ disease.
- Measurable disease as defined per RECIST v.1.1 OR at least one lytic or mixed (lytic
+ sclerotic) bone lesion with a soft tissue component that can be assessed by CT or
MRI.
- Eastern Cooperative Oncology Group performance status of 0 or 1.
- Adequate organ and marrow function.
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory
tests, and other study procedures.
INFORMATION FOR TRIAL PARTICIPANTS
Participants can join the trial if they:
- Have breast cancer that cannot be treated with surgery or radiation
- Have breast cancer that has already spread into other parts of the body at the time
of diagnosis, or has come back after at least 2 years of a standard endocrine
treatment
- Have ER proteins but not overexpression of HER2 protein in their tumors
- Have never received any type of cancer therapy that affects the whole body for
advanced breast cancer
- Are able to do their daily activities
EXCLUSION CRITERIA
Full list of exclusion criteria
- Previous neoadjuvant or adjuvant treatment with an AI treatment +/- CDK4/6 inhibitor
with disease recurrence while on or within 12 months of completing treatment.
- Prior exposure to AZD9833, other investigational SERDs/endocrine agents or
fulvestrant.
- Participation in another clinical study with a study treatment or investigational
medicinal device administered in the last 4 weeks prior to randomization or
concurrent enrollment in another clinical study, unless it is an observational
(non-interventional) clinical study or during the follow-up period of an
interventional study.
- Advanced, symptomatic, visceral spread, that are at risk of life-threatening
complications in the short term and/or impending visceral crisis
- Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis,
or leptomeningeal disease.
- Any clinically important and symptomatic heart disease .
- Currently pregnant (confirmed with positive pregnancy test) or breast-feeding.
- As judged by the investigator, any evidence of diseases (such as severe or
uncontrolled systemic diseases, renal transplant and active bleeding 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.
- Any concurrent anti-cancer treatment.
- Active infection including tuberculosis, HBV and HCV.
INFORMATION FOR TRIAL PARTICIPANTS
Participants cannot join the trial if they:
- Have uncontrolled cancer that has spread to the brain or the spinal cord
- Have received certain treatments for cancer in the past but the cancer came back
within 1 year
- Had certain types of tumors in the past, which the study doctors think could come
back
- Are currently taking any treatment for cancer or are taking medications or
supplements that affect certain proteins in the body
- Have any major health problem, infection, or surgery that could make it difficult or
dangerous to participate in this trial, such as tuberculosis, HIV, heart problems,
or a kidney transplant
The above information is not intended to contain all considerations relevant to a
patient's potential participation in a clinical trial. (ICTRP)
not available
Primary and secondary end points
Progression-free survival (PFS) assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST) version 1.1 (ICTRP)
Overall survival (OS);Second progression-free survival (PFS2);Objective response rate (ORR) assessed by the Investigator as defined by RECIST version 1.1;Duration of response (DoR) assessed by the Investigator as defined by RECIST version 1.1;Time to chemotherapy (TTC);Time to first subsequent anti-cancer therapy (TFST);Clinical benefit rate at 24 weeks (CBR24);Time to second subsequent therapy (TSST);Plasma concentration of AZD9833 at specified timepoints;Change from baseline in EORTC QLQ-C30 scale scores;Change from baseline in EORTC QLQ-BR45 scale scores (ICTRP)
Registration date
23.12.2020 (ICTRP)
Incorporation of the first participant
not available
Secondary sponsors
not available
Additional contacts
AstraZeneca Clinical Study Information Center, information.center@astrazeneca.com, 1-877-240-9479 (ICTRP)
Secondary trial IDs
2020-002276-12, D8532C00001 (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/study/NCT04711252 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available