A Phase III study to evaluate a switch to Camizestrant (AZ9833) and a CDK4/6 inhibitor compared to continuation of standard treatment with an aromatase inhibitor and CDK4/6 inhibitor in patients with HR-positive/HER-negative metastatic breast cancer and ctDNA evidence of an ESR1 mutation without disease progression during first-line therapy (SERENA-6)
Zusammenfassung der Studie
This study will be conducted at approximately 220 hospitals in around 25 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 HR-positive/HER-negative breast cancer with metastases. This trial aims to find out whether it is better to replace the standard aromatase inhibitor with Camizestrant in standard treatment. There is currently no way to determine which patients will benefit the longest from standard treatment. It may be possible to identify patients for whom treatment is no longer effective by searching for cancer DNA in their blood to detect changes in the genes of the cancer disease. These changes exist before a tumor can be visualized with standard imaging techniques (e.g., with CT or MRI scans). Approximately 2000 patients will be included in the first screening of the study. The study is divided into different phases: The first screening assesses whether participants are eligible for the study. Once the first screening is completed, the monitoring phase begins if eligibility is confirmed. This phase serves to check for changes in the genes of the cancer disease (ESR1 mutation). If no ESR1 mutations are present, the monitoring phase continues until the cancer progresses or enough patients are enrolled in the study. If ESR1 mutations are detected, the second screening will assess further eligibility for treatment. It is planned that 300 patients worldwide (3 patients in Switzerland) will receive this treatment as part of the study. Treated patients will be randomly assigned in a 1:1 ratio to one of two treatment groups. Treatment in both groups will continue until the disease progresses.
(BASEC)
Untersuchte Intervention
Patients will be randomly assigned in a 1:1 ratio to one of the following two treatment groups: Group A: Camizestrant + Placebo (aromatase inhibitor) + CDK4/6 inhibitor Group B: Aromatase inhibitor + Placebo (Camizestrant) + CDK4/6 inhibitor Allowed aromatase inhibitors are: Letrozole or Anastrozole Allowed CDK4/6 inhibitors are: Palbociclib or Abemaciclib A placebo is a substance that looks like the investigational drug but contains no active ingredient. The use of a placebo ensures that neither the investigator nor the patients know which treatment they are receiving. Medications in this study are taken orally (by mouth) in the form of a tablet or capsule.
(BASEC)
Untersuchte Krankheit(en)
Breast cancer with metastases (metastatic), HR-positive/HER-negative
(BASEC)
The main inclusion criteria are: 1. Participants must have a certain type of breast cancer that is HR-positive/HER-negative and locally advanced. 2. Treatment with aromatase and CDK4/6 inhibitors for at least 6 months. 3. Evidence of a change in the DNA of the cancer disease in the blood (ESR1 mutation) 4. No progression of the disease detected by imaging (CT or MRI). 5. Written informed consent provided. (BASEC)
Ausschlusskriterien
The main exclusion criteria: Patients 1. who are only treated with hormone therapy (aromatase inhibitors, Tamoxifen, Fulvestrant). 2. who are treated with aromatase inhibitors and Ribociclib. 3. who have no lesions that can be detected by imaging (CT/MRI). 4. who have a medical or genetically induced heart disease. (BASEC)
Studienstandort
Bern, Chur, Winterthur
(BASEC)
Sponsor
AstraZeneca AB
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Silviya Cantatore
+41 (0) 41 725 75 75
silviya.cantatore@clutterastrazeneca.comAstraZeneca AB
(BASEC)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Bern
(BASEC)
Datum der Bewilligung durch die Ethikkommission
28.07.2022
(BASEC)
ICTRP Studien-ID
NCT04964934 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
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 ESR1 Mutation Without Disease Progression During 1L Treatment with Aromatase Inhibitor + CDK4/6 Inhibitor (BASEC)
Wissenschaftlicher Titel
A Phase III, Double-blind, Randomised Study to Assess Switching to AZD9833 (a Next Generation, Oral SERD) + CDK4/6 Inhibitor 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 (ICTRP)
Öffentlicher Titel
Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6) (ICTRP)
Untersuchte Krankheit(en)
ER-Positive HER2-Negative Breast Cancer (ICTRP)
Untersuchte Intervention
Drug: AZD9833Drug: AZD9833 PlaceboDrug: AnastrozoleDrug: Anastrozole placeboDrug: LetrozoleDrug: Letrozole placeboDrug: PalbociclibDrug: AbemaciclibDrug: Luteinizing hormone-releasing hormone (LHRH) agonistDrug: Ribociclib (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator). (ICTRP)
Ein-/Ausschlusskriterien
INCLUSION CRITERIA:
INFORMATION FOR TRIAL PARTICIPANTS - Participants can join the trial if they:
- Have advanced breast cancer that is not able to be treated with surgery or
radiation
- Have an ESR1 mutation in their cancer
- Have breast cancer that is HR-positive and HER2-negative
- Are currently being treated with a CDK4/6 inhibitor and an AI and have been taking
these drugs for at least 6 months
- Have not had their cancer get worse after taking an AI and CDK4/6 inhibitor
- Are able to do their daily activities
- Are at least 18.
Full list of 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,
abemaciclib or ribociclib) LHRH as the initial endocrine based treatment for
advanced disease
- Eastern Cooperative Oncology Group performance status of 0 or 1
- ESR1m detected by central testing of ctDNA with Guardant360 CDx
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory
tests, and other study procedures
- Adequate organ and marrow function.
EXCLUSION CRITERIA:
INFORMATION FOR TRIAL PARTICIPANTS - Participants cannot join the trial if they:
- Had certain types of tumors in the past that may come back
- Are currently taking any other treatments for their cancer or other conditions
including hormone replacements, medications, or supplements that could interfere
with the trial treatment
- Have or have had any major health problem, infection, or recent surgery that could
make it difficult or dangerous to participate in this trial.
Full list of 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. (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Progression-free survival (PFS) assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST version 1.1) (ICTRP)
Progression-free survival 2 (PFS2);Overall survival (OS);Chemotherapy free survival;Objective response rate (ORR) assessed by the Investigator as defined by RECIST version 1.1;Clinical benefit rate at 24 weeks (CBR24);Change from baseline in EORTC QLQ-C30 scale scores;Change from baseline in EORTC QLQ-BR23 scale scores;Plasma concentration of AZD9833 at specified timepoints (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
AstraZeneca Clinical Study Information Center, information.center@astrazeneca.com, 1-877-240-9479 (ICTRP)
Sekundäre IDs
2023-503990-39-00, 2021-000546-17, D8534C00001 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/study/NCT04964934 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar