Studio per valutare la sicurezza e la tollerabilità di Camizestrant in combinazione con Atirmociclib nelle donne con carcinoma mammario avanzato (SERENA-1b)
Uno studio di fase IIa, in aperto, per valutare la sicurezza, la farmacocinetica e l'efficacia preliminare di Camizestrant in combinazione con Atirmociclib in partecipanti con carcinoma mammario avanzato ER-positivo, HER2-negativo (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.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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
Tipo di studio
Iscrizione (Stimato)
Fase
- Fase 2
Contatti e Sedi
Contatto studio
- Nome: AstraZeneca Clinical Study Information Center
- Numero di telefono: 1-877-240-9479
- Email: information.center@astrazeneca.com
Luoghi di studio
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Cambridge, Regno Unito, CB2 0QQ
- Reclutamento
- Research Site
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London, Regno Unito, EC1M6BQ
- Reclutamento
- Research Site
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Manchester, Regno Unito, M20 4GJ
- Reclutamento
- Research Site
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Missouri
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St Louis, Missouri, Stati Uniti, 63108
- Reclutamento
- Research Site
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Rhode Island
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East Providence, Rhode Island, Stati Uniti, 02915
- Reclutamento
- Research Site
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Tennessee
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Nashville, Tennessee, Stati Uniti, 37203
- Reclutamento
- Research Site
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Main Inclusion Criteria:
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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.
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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.
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Eastern cooperative oncology group (ECOG)/World Health Organization (WHO) performance status 0 to 1, and a minimum life expectancy of 12 weeks.
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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.
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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.
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Histological or cytological confirmation of adenocarcinoma of the breast.
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Participants of childbearing potential must agree to use one highly effective contraceptive measure.
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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.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: N / A
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Sperimentale: 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. |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Number of participants with adverse events (AEs) and serious AEs
Lasso di tempo: Up to Post-Treatment Follow up (Day 30 Post Dose)
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To investigate the safety and tolerability of camizestrant in combination with atirmociclib. |
Up to Post-Treatment Follow up (Day 30 Post Dose)
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Maximum concentration observed (Cmax)
Lasso di tempo: At pre-defined intervals from Day -1 to Day 57
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To characterize the PK profile and parameters of atirmociclib. |
At pre-defined intervals from Day -1 to Day 57
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Area under plasma concentration-time curve from time 0 to infinity (AUCinf)
Lasso di tempo: 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
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Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast)
Lasso di tempo: 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
|
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Time to reach maximum (peak) plasma concentration following drug administration (tmax)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: At pre-defined intervals from Day -1 to Day 57
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To characterize the PK profile and parameters of atirmociclib. |
At pre-defined intervals from Day -1 to Day 57
|
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Apparent volume of distribution at steady state (Vss/F)
Lasso di tempo: 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
|
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Apparent volume of distribution based on the terminal phase (Vz/F)
Lasso di tempo: 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
|
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Maximum concentration observed at steady state (Cssmax)
Lasso di tempo: 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
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Area under the curve from 0 to the end of dosing interval (AUC0-tau)
Lasso di tempo: 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
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Area under the curve from 0 to the end of dosing interval at steady state (AUCss0-tau)
Lasso di tempo: 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
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Time to reach maximum plasma concentration at steady state (tssmax)
Lasso di tempo: At pre-defined intervals from Day -1 to Day 57
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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
|
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Objective Response Rate (ORR)
Lasso di tempo: Up to 2 years
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To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib. |
Up to 2 years
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Duration of Response (DOR)
Lasso di tempo: Up to 2 years
|
To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib. |
Up to 2 years
|
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Clinical Benefit Rate at 24 Weeks (CBR24)
Lasso di tempo: At 24 weeks
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To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib. |
At 24 weeks
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Percentage change in tumor size
Lasso di tempo: Up to 2 years
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To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib. |
Up to 2 years
|
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Progression Free Survival (PFS)
Lasso di tempo: Up to 2 years
|
To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib. |
Up to 2 years
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Progression-free survival landmark 6 months (PFSLM6m)
Lasso di tempo: At 6 months
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To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib. |
At 6 months
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Progression-free survival landmark 12 months (PFSLM12m)
Lasso di tempo: At 12 months
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To assess the preliminary anti-tumor activity and efficacy of camizestrant in combination with atirmociclib. |
At 12 months
|
Collaboratori e investigatori
Sponsor
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Stimato)
Completamento dello studio (Stimato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- D853CC00001
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Descrizione del piano IPD
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.
Periodo di condivisione IPD
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.
Criteri di accesso alla condivisione IPD
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.
Tipo di informazioni di supporto alla condivisione IPD
- STUDIO_PROTOCOLLO
- LINFA
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .