TACTIVE-U: Un estudio para conocer el medicamento del estudio (Vepdegestrant) cuando se administra con otros medicamentos en personas con cáncer de mama avanzado o metastásico. (Subestudio C)
TACTIVE-U: UN ESTUDIO INTERVENCIONAL DE SEGURIDAD Y EFICACIA FASE 1B/2, ESTUDIO PARAGUAS DE ETIQUETA ABIERTA PARA INVESTIGAR LA TOLERABILIDAD, PK Y ACTIVIDAD ANTITUMORAL DEL VEPDEGESTRANTE (ARV-471/PF-07850327), UNA QUIMERA DIRIGIDA A LA PROTEÓLISIS ORAL, EN COMBINACIÓN CON OTRAS TRATAMIENTOS ANTICÁNCER EN PARTICIPANTES DE 18 AÑOS Y MAYORES CON CÁNCER DE MAMA AVANZADO O METASTÁSICO ER+, SUBESTUDIO C (ARV-471 EN COMBINACIÓN CON SAMURACICLIB)
The purpose of this study is to learn about the safety and effects of the study medicine called vepdegestrant. The safety and effects of vepdegestrant will be see when given with other medicines. Vepdegestrant is studied to see if it can be a possible treatment for advanced metastatic breast cancer. This type of cancer would have spread from where it started (breast) to other parts of the body and would be tough to treat.
The study is seeking for participants who have breast cancer that:
- is hard to treat (advanced) and may have spread to other organs (metastatic). is sensitive to hormonal therapy (it is called estrogen receptor positive).
- is no longer responding to treatments taken before starting this study.
This study is divided into separate sub-studies.
For Sub-Study C:
All the participants will receive vepdegestrant and a medicine called samuraciclib.
Vepdegestrant and samuraciclib will be taken once in a day by mouth. The medicines will be taken at home. The experience of people receiving the study medicines will be studied. This will help see if the study medicine is safe and effective.
Participant will continue to take vepdegestrant and samuraciclib until:
- their cancer is no longer responding, or
- side effects become too severe.
They will have visits at the study clinic about every 4 weeks.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
C4891024 is a prospective, open-label, multicenter, Phase 1b/2 sub-study to evaluate the safety, antitumor activity, and PK of ARV-471 with samuraciclib in the treatment of participants with A/MBC. The sub-study is part of Umbrella platform, TACTIVE-U, comprising multiple sub-studies that independently evaluate ARV-471 in participants with Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Advanced or Metastatic Breast Cancer. ARV-471 will act as the backbone therapy given in combination with other anticancer agents thought to have clinical relevance in ER+ breast cancer.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Bruxelles-capitale, Région de
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Anderlecht, Bruxelles-capitale, Région de, Bélgica, 1070
- Institut Jules Bordet
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Arkansas
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Fayetteville, Arkansas, Estados Unidos, 72703
- Highlands Oncology Group
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Rogers, Arkansas, Estados Unidos, 72758
- Highlands Oncology Group
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Springdale, Arkansas, Estados Unidos, 72762
- Highlands Oncology Group
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California
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Palo Alto, California, Estados Unidos, 94304
- Stanford Women's Cancer Center
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Palo Alto, California, Estados Unidos, 94304
- Clinical and Translational Research Unit (CTRU)
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Palo Alto, California, Estados Unidos, 94304
- Stanford Cancer Institute - Clinical Trials Office
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Colorado
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Fort Collins, Colorado, Estados Unidos, 80524
- UCHealth Poudre Valley Hospital
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Fort Collins, Colorado, Estados Unidos, 80528
- UCHealth Harmony
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Greeley, Colorado, Estados Unidos, 80634
- UCHealth Greeley Hospital
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Loveland, Colorado, Estados Unidos, 80538
- UCHealth - Medical Center of the Rockies
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Illinois
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Shiloh, Illinois, Estados Unidos, 62269
- Memorial Hospital East
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Shiloh, Illinois, Estados Unidos, 62269
- Siteman Cancer Center - Shiloh
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Missouri
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City of Saint Peters, Missouri, Estados Unidos, 63376
- Siteman Cancer Center - St Peters
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Creve Coeur, Missouri, Estados Unidos, 63141
- Siteman Cancer Center - West County
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Florissant, Missouri, Estados Unidos, 63031
- Siteman Cancer Center - North County
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St Louis, Missouri, Estados Unidos, 63110
- Barnes-Jewish Hospital
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St Louis, Missouri, Estados Unidos, 63110
- Washington University School of Medicine
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St Louis, Missouri, Estados Unidos, 63110
- Washington University School of Medicine - Siteman Cancer Center
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St Louis, Missouri, Estados Unidos, 63129
- Siteman Cancer Center - South County
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Côte-d'or
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Dijon, Côte-d'or, Francia, 21079
- Centre Georges François Leclerc
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Roma, Italia, 00168
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore
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Lombardy
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Monza, Lombardy, Italia, 20900
- Fondazione IRCCS San Gerardo dei Tintori
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Histological or cytological diagnosis of breast cancer. At time of enrollment this must not be amendable to surgical resection with curative intent (≥1% ER+ stained cells as per local practice on the most recent tumor biopsy HER2- tumor by IHC or in-situ hybridization per ASCO/CAP).
- prior anticancer therapies: up to 2 lines of prior therapies for advanced/metastatic disease; 1 line of any CDK4/6 inhibitor-based regimen is required (in any setting eg adjuvant, metastatic)
- at least 1 measurable lesion as defined by RECIST v1.1.
- ECOG PS ≤1.
Exclusion Criteria:
- visceral crisis at risk of life-threatening complications in the short term
- known history of drug-induced pneumonitis or other significant symptomatic deterioration of lung functions.
- newly diagnosed brain metastases, or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease. Participants with a history of CNS metastases or cord compression are eligible if they have been definitively treated, clinically stable and discontinued anti-seizure medications and corticosteroids for at least 28 days prior to enrollment in the of study.
- history of any other tumor malignancies within the past 3 years, except for the following: (1) adequately treated basal or squamous cell carcinoma of the skin; (2) curatively treated in situ carcinoma of the cervix.
- inflammatory breast cancer
- impaired cardiovascular function or clinically significant cardiovascular diseases
- concurrent administration of medications, food, or herb supplements that are strong inhibitors/inducers of CYP3A, strong CYP2D6 inhibitors and drugs known to predispose to Torsade de Pointes or QT interval prolongation.
- renal impairment, not adequate liver function and/or bone marrow function
- known active infection
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación Secuencial
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: ARV-471 in combination with Samuraciclib
ARV-471 administered orally QD continuously and Samuraciclib administered orally QD continuously on 28-day cycles |
Daily oral dosages of ARV-471 continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 days
Otros nombres:
Daily oral dosages of Samuraciclib continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 days |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Phase 1b: Number of Participants With Dose Limiting Toxicities
Periodo de tiempo: 28 days
|
Dose Limiting Toxicities rate for ARV-471 in combination with Samuraciclib, estimated based on data from DLT-evaluable participants during the DLT observation period (Cycle 1). |
28 days
|
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Drug Drug Interaction: To evaluate the effect of samuraciclib on PK of ARV 471.
Periodo de tiempo: From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days)
|
Steady-state Area under the plasma concentration versus time curve (AUCtau) of ARV-471 with and without coadministration of samuraciclib |
From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days)
|
|
Drug Drug Interaction: To evaluate the effect of samuraciclib on PK of ARV 471.
Periodo de tiempo: From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days)
|
Steady-state Peak Plasma concentration ( Cmax) of ARV-471 with and without coadministration of samuraciclib |
From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days)
|
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Phase 2: Percentage of Participants With Objective Response by investigator assessment
Periodo de tiempo: Up to approximately 1 year
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Objective response (OR) refers to confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. as determined by investigator assessment. |
Up to approximately 1 year
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Drug Drug Interaction: • To evaluate the effect of ARV 471 on PK of samuraciclib.
Periodo de tiempo: From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days))
|
Single dose AUC0-72 of samuraciclib with and without coadministration of ARV 471. |
From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days))
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Drug Drug Interaction: • To evaluate the effect of ARV 471 on PK of samuraciclib.
Periodo de tiempo: From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days))
|
Single dose Cmax of samuraciclib with and without coadministration of ARV 471. |
From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days))
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Phase 1b, Drug drug interaction and Phase 2: Evaluation of Safety and Tolerability of ARV-471 in combination with Samuraciclib
Periodo de tiempo: First study drug dose through a minimum of 28 Days After Last study drug administration
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AEs as characterized by type, frequency, intensity as graded by NCI CTCAE version 5.0, timing, seriousness, and relationship to ARV-471 in combination with samuraciclib. Laboratory test abnormalities as characterized by type, frequency, intensity (as graded by NCI CTCAE version 5.0), and timing. Changes from baseline for the ECG parameters heart rate, QTcF, PR interval, and QRS complex will be summarized by treatment and time. The frequency of uncorrected QT values above 500 ms will be tabulated. |
First study drug dose through a minimum of 28 Days After Last study drug administration
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Phase 1b: To evaluate antitumor activity of ARV-471 in combination with samuraciclib
Periodo de tiempo: Up to approximately 1 year
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Objective response (OR) refers to confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. as determined by investigator assessment. |
Up to approximately 1 year
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Phase 1b and Phase 2: Duration of Response by investigator assessment.
Periodo de tiempo: Up to approximately 1 year
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Duration of Response (DoR) is defined for participants with confirmed OR (CR or PR) as the time from the first documentation of OR to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. |
Up to approximately 1 year
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Phase 1b and Phase2: Percentage of participants with Clinical Benefit Response by investigator assessment.
Periodo de tiempo: Up to approximately 1 year
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Clinical Benefit Response (CBR) is defined as the proportion of participants with Best Overall Response of confirmed CR or PR at any time, or Stable Disease (SD) ≥24 weeks |
Up to approximately 1 year
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Phase 1b and Phase 2: Progression Free Survival by investigator assessment.
Periodo de tiempo: Up to approximately 1 year
|
Progression Free Survival (PFS) is defined as the time from the date of first dose of study interventions to the date of first documentation of PD or death due to any cause, whichever occurs first. |
Up to approximately 1 year
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Phase 1b and Phase 2: Plasma concentrations of ARV-471 and samuraciclib.
Periodo de tiempo: At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)
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To evaluate the plasma exposure of ARV-471 and samuraciclib when ARV-471 and samuraciclib are given in combination. |
At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)
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Phase 1b: Evaluation of effect of samuraciclib on PK of ARV-471
Periodo de tiempo: At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)
|
AUCtau of ARV-471 with and without co-administration of samuraciclib |
At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)
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Phase 1b: Evaluation of effect of samuraciclib on PK of ARV-471
Periodo de tiempo: At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)
|
Cmax of ARV-471 with and without co-administration of samuraciclib |
At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)
|
|
Phase 2:ctDNA plasma quantitative changes from pre-treatment
Periodo de tiempo: At predefined intervals throughout the treatment period, up to cycle 3 (each cycle is 28 days) and end of treatment
|
To assess changes from baseline levels in plasma ctDNA with treatment and to evaluate potential predictability of their associations with clinical outcomes. |
At predefined intervals throughout the treatment period, up to cycle 3 (each cycle is 28 days) and end of treatment
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Phase 2: To evaluate the correlation between TP53 mutation status and antitumor activity
Periodo de tiempo: Screening
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Participants classified on basis of pathological TP53 mutation detected or not detected. |
Screening
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Phase 2: Overall Survival
Periodo de tiempo: Through study completion, up to approximately 3 year
|
Overall Survival (OS) is defined as the time from the date of first dose of study interventions to the date of death due to any cause |
Through study completion, up to approximately 3 year
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Director de estudio: Pfizer CT.gov Call Center, Pfizer
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- C4891024
- 2023-507125-41-00 (Identificador de registro: CTIS (EU))
- 2023 (Subvención/contrato del NIH de EE. UU.)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .