TACTIVE-U：一项了解晚期或转移性乳腺癌患者与其他药物联合使用的研究药物（Vepdegestrant）的研究。 （子研究 C）
TACTIVE-U：一项干预性安全性和有效性 1B/2 期、开放标签伞式研究，旨在调查 VEPDEGESTRANT (ARV-471/PF-07850327) 的耐受性、PK 和抗肿瘤活性，这是一项针对嵌合体的口服蛋白水解酶其他18 岁及以上患有 ER+ 晚期或转移性乳腺癌参与者的抗癌治疗，子研究 C（ARV-471 与 SAMURACICLIB 联用）
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.
研究概览
详细说明
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.
研究类型
注册 (实际的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习地点
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Roma、意大利、00168
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore
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Lombardy
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Monza、Lombardy、意大利、20900
- Fondazione IRCCS San Gerardo dei Tintori
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Bruxelles-capitale, Région de
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Anderlecht、Bruxelles-capitale, Région de、比利时、1070
- Institut Jules Bordet
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Côte-d'or
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Dijon、Côte-d'or、法国、21079
- Centre Georges François Leclerc
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Arkansas
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Fayetteville、Arkansas、美国、72703
- Highlands Oncology Group
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Rogers、Arkansas、美国、72758
- Highlands Oncology Group
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Springdale、Arkansas、美国、72762
- Highlands Oncology Group
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California
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Palo Alto、California、美国、94304
- Stanford Women's Cancer Center
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Palo Alto、California、美国、94304
- Clinical and Translational Research Unit (CTRU)
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Palo Alto、California、美国、94304
- Stanford Cancer Institute - Clinical Trials Office
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Colorado
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Fort Collins、Colorado、美国、80524
- UCHealth Poudre Valley Hospital
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Fort Collins、Colorado、美国、80528
- UCHealth Harmony
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Greeley、Colorado、美国、80634
- UCHealth Greeley Hospital
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Loveland、Colorado、美国、80538
- UCHealth - Medical Center of the Rockies
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Illinois
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Shiloh、Illinois、美国、62269
- Memorial Hospital East
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Shiloh、Illinois、美国、62269
- Siteman Cancer Center - Shiloh
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Missouri
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City of Saint Peters、Missouri、美国、63376
- Siteman Cancer Center - St Peters
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Creve Coeur、Missouri、美国、63141
- Siteman Cancer Center - West County
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Florissant、Missouri、美国、63031
- Siteman Cancer Center - North County
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St Louis、Missouri、美国、63110
- Barnes-Jewish Hospital
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St Louis、Missouri、美国、63110
- Washington University School of Medicine
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St Louis、Missouri、美国、63110
- Washington University School of Medicine - Siteman Cancer Center
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St Louis、Missouri、美国、63129
- Siteman Cancer Center - South County
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
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
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：顺序分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：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
其他名称：
Daily oral dosages of Samuraciclib continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 days |
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Phase 1b: Number of Participants With Dose Limiting Toxicities
大体时间：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
|
|
Drug Drug Interaction: To evaluate the effect of samuraciclib on PK of ARV 471.
大体时间：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)
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Drug Drug Interaction: To evaluate the effect of samuraciclib on PK of ARV 471.
大体时间：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
大体时间：Up to approximately 1 year
|
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.
大体时间：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.
大体时间：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))
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Phase 1b, Drug drug interaction and Phase 2: Evaluation of Safety and Tolerability of ARV-471 in combination with Samuraciclib
大体时间：First study drug dose through a minimum of 28 Days After Last study drug administration
|
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
大体时间：Up to approximately 1 year
|
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
|
|
Phase 1b and Phase 2: Duration of Response by investigator assessment.
大体时间：Up to approximately 1 year
|
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.
大体时间：Up to approximately 1 year
|
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.
大体时间：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.
大体时间：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
大体时间：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
大体时间：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)
|
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Phase 2:ctDNA plasma quantitative changes from pre-treatment
大体时间：At predefined intervals throughout the treatment period, up to cycle 3 (each cycle is 28 days) and end of treatment
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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
大体时间：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
大体时间：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
|
合作者和调查者
赞助
调查人员
- 研究主任：Pfizer CT.gov Call Center、Pfizer
出版物和有用的链接
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他研究编号
- C4891024
- 2023-507125-41-00 (注册表标识符：CTIS (EU))
- 2023 (美国 NIH 拨款/合同)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
IPD 计划说明
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.
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
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