Studie zur Bewertung der Sicherheit und Verträglichkeit von Camizestrant in Kombination mit Atirmociclib bei Frauen mit fortgeschrittenem Brustkrebs (SERENA-1b)
Eine Phase-IIa-Open-label-Studie zur Bewertung der Sicherheit, Pharmakokinetik und vorläufigen Wirksamkeit von Camizestrant in Kombination mit Atirmociclib bei Teilnehmern mit ER-positivem, HER2-negativem fortgeschrittenem Brustkrebs (SERENA-1b)
A study to investigate camizestrant in combination with atirmociclib in participants with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with a cyclin dependent kinase 4/6 (CDK4/6) inhibitor.
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
This is a Phase IIa, sequential assignment, non- randomized, open-label treatment study to determine the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of camizestrant in combination with atirmociclib.
The single-arm study includes:
- Screening period
- Atirmociclib single dose period
- Doublet intervention period
- Post-treatment follow-up period
Studientyp
Einschreibung (Geschätzt)
Phase
- Phase 2
Kontakte und Standorte
Studienkontakt
- Name: AstraZeneca Clinical Study Information Center
- Telefonnummer: 1-877-240-9479
- E-Mail: information.center@astrazeneca.com
Studienorte
-
-
Missouri
-
St Louis, Missouri, Vereinigte Staaten, 63108
- Rekrutierung
- Research Site
-
-
Rhode Island
-
East Providence, Rhode Island, Vereinigte Staaten, 02915
- Rekrutierung
- Research Site
-
-
Tennessee
-
Nashville, Tennessee, Vereinigte Staaten, 37203
- Rekrutierung
- Research Site
-
-
-
-
-
Cambridge, Vereinigtes Königreich, CB2 0QQ
- Rekrutierung
- Research Site
-
London, Vereinigtes Königreich, EC1M6BQ
- Rekrutierung
- Research Site
-
Manchester, Vereinigtes Königreich, M20 4GJ
- Rekrutierung
- Research Site
-
-
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
Main Inclusion Criteria:
-
Participants with advanced adenocarcinoma of the breast and must have received prior adequate therapy in accordance with local practice for their tumor type and stage of disease.
-
Metastatic or locoregionally recurrent disease and radiological or objective evidence of progression on or after the last systemic therapy prior to starting investigational medicinal products.
-
Eastern cooperative oncology group (ECOG)/World Health Organization (WHO) performance status 0 to 1, and a minimum life expectancy of 12 weeks.
-
At least one lesion that is measurable and/or non-measurable, as per RECIST 1.1 and that can be accurately assessed at baseline and is suitable for repeated assessment by computed tomography (CT), magnetic resonance imaging (MRI), or plain X-ray, or clinical examination.
-
Menopausal status
- Pre-menopausal women must start GnRH agonist therapy at least 4 weeks before study treatment and continue throughout the study.
- Post-menopausal women must meet one of these criteria: bilateral oophorectomy, age ≥60 years, age ≥50 years with ≥12 months amenorrhea and intact uterus without hormonal therapy, or age <60 years with ≥12 months amenorrhea and post-menopausal hormone levels.
-
Histological or cytological confirmation of adenocarcinoma of the breast.
-
Participants of childbearing potential must agree to use one highly effective contraceptive measure.
-
Documentation of ER-positive tumor irrespective of progesterone receptor status.
Main Exclusion Criteria:
- A participant who has received 2 or more lines of CDK4/6 inhibitors in the advanced disease setting.
- A participant who has received prior camizestrant or atirmociclib treatment in the advanced disease setting.
- Patients previously treated with other next generation selective estrogen receptor degrader (SERDs) or other experimental ETs in the advanced disease setting.
- Patients previously treated with other experimental cyclin-dependent kinase (CDK) inhibitors are not eligible.
- Inability to swallow oral medications.
- Any unresolved toxicities of Grade ≥ 2 from prior anti-cancer therapy (with the exception of alopecia).
- Presence of life-threatening metastatic visceral disease.
- Any evidence of severe or uncontrolled systemic diseases.
- Contraindication to or known intolerance/hypersensitivity of/to camizestrant or atirmociclib.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: N / A
- Interventionsmodell: Einzelgruppenzuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
Experimental: Camizestrant + Atirmociclib
Participants will receive a single dose of atirmociclib on Day -1 followed by combination of camizestrant and atirmociclib from Day 1. |
Camizestrant will be administered orally. Atirmociclib will be administered orally. |
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Number of participants with adverse events (AEs) and serious AEs
Zeitfenster: Up to Post-Treatment Follow up (Day 30 Post Dose)
|
To investigate the safety and tolerability of camizestrant in combination with atirmociclib. |
Up to Post-Treatment Follow up (Day 30 Post Dose)
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Maximum concentration observed (Cmax)
Zeitfenster: At pre-defined intervals from Day -1 to Day 57
|
To characterize the PK profile and parameters of atirmociclib. |
At pre-defined intervals from Day -1 to Day 57
|
|
Area under plasma concentration-time curve from time 0 to infinity (AUCinf)
Zeitfenster: At pre-defined intervals from Day -1 to Day 57
|
To characterize the PK profile and parameters of atirmociclib. |
At pre-defined intervals from Day -1 to Day 57
|
|
Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast)
Zeitfenster: At pre-defined intervals from Day -1 to Day 57
|
To characterize the PK profile and parameters of atirmociclib. |
At pre-defined intervals from Day -1 to Day 57
|
|
Time to reach maximum (peak) plasma concentration following drug administration (tmax)
Zeitfenster: At pre-defined intervals from Day -1 to Day 57
|
To characterize the PK profile and parameters of atirmociclib. |
At pre-defined intervals from Day -1 to Day 57
|
|
Terminal elimination rate constant (λz)
Zeitfenster: At pre-defined intervals from Day -1 to Day 57
|
To characterize the PK profile and parameters of atirmociclib. |
At pre-defined intervals from Day -1 to Day 57
|
|
Terminal elimination half-life (t½λz)
Zeitfenster: At pre-defined intervals from Day -1 to Day 57
|
To characterize the PK profile and parameters of atirmociclib. |
At pre-defined intervals from Day -1 to Day 57
|
|
Apparent total body clearance (CL/F)
Zeitfenster: At pre-defined intervals from Day -1 to Day 57
|
To characterize the PK profile and parameters of atirmociclib. |
At pre-defined intervals from Day -1 to Day 57
|
|
Apparent volume of distribution at steady state (Vss/F)
Zeitfenster: At pre-defined intervals from Day -1 to Day 57
|
To characterize the PK profile and parameters of atirmociclib. |
At pre-defined intervals from Day -1 to Day 57
|
|
Apparent volume of distribution based on the terminal phase (Vz/F)
Zeitfenster: At pre-defined intervals from Day -1 to Day 57
|
To characterize the PK profile and parameters of atirmociclib. |
At pre-defined intervals from Day -1 to Day 57
|
|
Maximum concentration observed at steady state (Cssmax)
Zeitfenster: At pre-defined intervals from Day -1 to Day 57
|
To characterise the PK profile and parameters of atirmociclib and camizestrant after administration in combination with each other. |
At pre-defined intervals from Day -1 to Day 57
|
|
Area under the curve from 0 to the end of dosing interval (AUC0-tau)
Zeitfenster: At pre-defined intervals from Day -1 to Day 57
|
To characterise the PK profile and parameters of atirmociclib and camizestrant after administration in combination with each other. |
At pre-defined intervals from Day -1 to Day 57
|
|
Area under the curve from 0 to the end of dosing interval at steady state (AUCss0-tau)
Zeitfenster: At pre-defined intervals from Day -1 to Day 57
|
To characterise the PK profile and parameters of atirmociclib and camizestrant after administration in combination with each other. |
At pre-defined intervals from Day -1 to Day 57
|
|
Time to reach maximum plasma concentration at steady state (tssmax)
Zeitfenster: At pre-defined intervals from Day -1 to Day 57
|
To characterise the PK profile and parameters of atirmociclib and camizestrant after administration in combination with each other. |
At pre-defined intervals from Day -1 to Day 57
|
|
Objective Response Rate (ORR)
Zeitfenster: Up to 2 years
|
To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib. |
Up to 2 years
|
|
Duration of Response (DOR)
Zeitfenster: Up to 2 years
|
To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib. |
Up to 2 years
|
|
Clinical Benefit Rate at 24 Weeks (CBR24)
Zeitfenster: At 24 weeks
|
To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib. |
At 24 weeks
|
|
Percentage change in tumor size
Zeitfenster: Up to 2 years
|
To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib. |
Up to 2 years
|
|
Progression Free Survival (PFS)
Zeitfenster: Up to 2 years
|
To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib. |
Up to 2 years
|
|
Progression-free survival landmark 6 months (PFSLM6m)
Zeitfenster: At 6 months
|
To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib. |
At 6 months
|
|
Progression-free survival landmark 12 months (PFSLM12m)
Zeitfenster: At 12 months
|
To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib. |
At 12 months
|
Mitarbeiter und Ermittler
Sponsor
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- D853CC00001
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Beschreibung des IPD-Plans
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
IPD-Sharing-Zeitrahmen
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD-Sharing-Zugriffskriterien
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Art der unterstützenden IPD-Freigabeinformationen
- STUDIENPROTOKOLL
- SAFT
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .