TACTIVE-U: 進行性または転移性乳がん患者に他の薬剤と併用投与した場合の治験薬（ベプデゲストラント）について学ぶための研究。 (サブ研究C)
TACTIVE-U: 介入の安全性と有効性フェーズ 1B/2、経口タンパク質分解を標的とするキメラであるベプデゲストラント (ARV-471/PF-07850327) の忍容性、PK、抗腫瘍活性を組み合わせて調査する非盲検アンブレラ試験他の人とER+の進行性または転移性乳がんを患う18歳以上の参加者における抗がん剤治療、サブ研究C（ARV-471とサムラシクリブの併用）
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.
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究場所
-
-
Arkansas
-
Fayetteville、Arkansas、アメリカ、72703
- Highlands Oncology Group
-
Rogers、Arkansas、アメリカ、72758
- Highlands Oncology Group
-
Springdale、Arkansas、アメリカ、72762
- Highlands Oncology Group
-
-
California
-
Palo Alto、California、アメリカ、94304
- Stanford Women's Cancer Center
-
Palo Alto、California、アメリカ、94304
- Clinical and Translational Research Unit (CTRU)
-
Palo Alto、California、アメリカ、94304
- Stanford Cancer Institute - Clinical Trials Office
-
-
Colorado
-
Fort Collins、Colorado、アメリカ、80524
- UCHealth Poudre Valley Hospital
-
Fort Collins、Colorado、アメリカ、80528
- UCHealth Harmony
-
Greeley、Colorado、アメリカ、80634
- UCHealth Greeley Hospital
-
Loveland、Colorado、アメリカ、80538
- UCHealth - Medical Center of the Rockies
-
-
Illinois
-
Shiloh、Illinois、アメリカ、62269
- Memorial Hospital East
-
Shiloh、Illinois、アメリカ、62269
- Siteman Cancer Center - Shiloh
-
-
Missouri
-
City of Saint Peters、Missouri、アメリカ、63376
- Siteman Cancer Center - St Peters
-
Creve Coeur、Missouri、アメリカ、63141
- Siteman Cancer Center - West County
-
Florissant、Missouri、アメリカ、63031
- Siteman Cancer Center - North County
-
St Louis、Missouri、アメリカ、63110
- Barnes-Jewish Hospital
-
St Louis、Missouri、アメリカ、63110
- Washington University School of Medicine
-
St Louis、Missouri、アメリカ、63110
- Washington University School of Medicine - Siteman Cancer Center
-
St Louis、Missouri、アメリカ、63129
- Siteman Cancer Center - South County
-
-
-
-
-
Roma、イタリア、00168
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore
-
-
Lombardy
-
Monza、Lombardy、イタリア、20900
- Fondazione IRCCS San Gerardo dei Tintori
-
-
-
-
Côte-d'or
-
Dijon、Côte-d'or、フランス、21079
- Centre Georges François Leclerc
-
-
-
-
Bruxelles-capitale, Région de
-
Anderlecht、Bruxelles-capitale, Région de、ベルギー、1070
- Institut Jules Bordet
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：順次割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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
他の名前：
Daily oral dosages of Samuraciclib continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 days |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Phase 1b: Number of Participants With Dose Limiting Toxicities
時間枠：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.
時間枠：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.
時間枠：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)
|
|
Phase 2: Percentage of Participants With Objective Response by investigator assessment
時間枠：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
|
|
Drug Drug Interaction: • To evaluate the effect of ARV 471 on PK of samuraciclib.
時間枠：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))
|
|
Drug Drug Interaction: • To evaluate the effect of ARV 471 on PK of samuraciclib.
時間枠：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))
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Phase 1b, Drug drug interaction and Phase 2: Evaluation of Safety and Tolerability of ARV-471 in combination with Samuraciclib
時間枠：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
|
|
Phase 1b: To evaluate antitumor activity of ARV-471 in combination with samuraciclib
時間枠：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.
時間枠：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
|
|
Phase 1b and Phase2: Percentage of participants with Clinical Benefit Response by investigator assessment.
時間枠：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
|
|
Phase 1b and Phase 2: Progression Free Survival by investigator assessment.
時間枠：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
|
|
Phase 1b and Phase 2: Plasma concentrations of ARV-471 and samuraciclib.
時間枠：At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)
|
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)
|
|
Phase 1b: Evaluation of effect of samuraciclib on PK of ARV-471
時間枠：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)
|
|
Phase 1b: Evaluation of effect of samuraciclib on PK of ARV-471
時間枠：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
時間枠：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
|
|
Phase 2: To evaluate the correlation between TP53 mutation status and antitumor activity
時間枠：Screening
|
Participants classified on basis of pathological TP53 mutation detected or not detected. |
Screening
|
|
Phase 2: Overall Survival
時間枠：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
|
協力者と研究者
スポンサー
捜査官
- スタディディレクター：Pfizer CT.gov Call Center、Pfizer
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- C4891024
- 2023-507125-41-00 (レジストリ識別子：CTIS (EU))
- 2023 (米国 NIH グラント/契約)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
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.
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。