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Tipifarnib 和 Alpelisib 在成人复发/转移性头颈部鳞状细胞癌 (R/M HNSCC) 中的联合试验

2026年8月25日 更新者：Kura Oncology, Inc.

一项 1/2 期开放标签、生物标志物定义的队列试验，以评估 Tipifarnib 和 Alpelisib 的安全性、确定推荐的联合剂量和评估早期抗肿瘤活性，用于治疗 HRAS 过度表达和/或 PIK3CA- 的成人参与者突变和/或 - 放大的复发性/转移性头颈部鳞状细胞癌

法尼基转移酶抑制剂替比法尼和 PI3K 抑制剂 alpelisib 在患有复发/转移性头颈部鳞状细胞癌 (HNSCC) 且肿瘤过度表达 HRAS 蛋白和/或 PIK3CA 突变和/或 PIK3CA 扩增。

研究概览

地位

完全的

条件

干预/治疗

研究类型

介入性

注册 (实际的)

45

阶段

  • 阶段2
  • 阶段1

扩展访问

可用的 查看扩展访问记录。

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 美国
    • California
      • Duarte、California、美国、91010
        • City of Hope Comprehensive Cancer Center
    • Florida
      • Orlando、Florida、美国、32827
        • Lake Nona DDU (Florida Cancer Specialists)
    • Maryland
      • Baltimore、Maryland、美国、21201
        • University of Maryland School of Medicine (Marlene and Stewart Greenebaum Comprehensive Cancer Center)
      • Baltimore、Maryland、美国、21231
        • Johns Hopkins University School of Medicine (Sidney Kimmel Comprehensive Cancer Center)
    • Massachusetts
      • Boston、Massachusetts、美国、02215
        • Dana-Farber Cancer Institute (Head and Neck Cancer Treatment Center)
    • Missouri
      • St Louis、Missouri、美国、63110
        • Washington University, School of Medicine
    • New York
      • New York、New York、美国、10065
        • Memorial Sloan Kettering Cancer Center
    • Pennsylvania
      • Pittsburgh、Pennsylvania、美国、15232
        • UPMC Hillman Cancer Center
    • Texas
      • Dallas、Texas、美国、75390
        • UT Southwestern Medical Center (Harold C. Simmons Comprehensive Cancer Center)
      • Houston、Texas、美国、77030
        • University of Texas MD Anderson Cancer Center
    • Wisconsin
      • Madison、Wisconsin、美国、53792
        • University of Wisconsin Carbone Cancer Center

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

描述

纳入标准：

  1. 至少 18 岁。
  2. 经组织学证实的鳞状组织学头颈癌不适合以治愈为目的的局部治疗（手术或放疗加或不加化学疗法）。
  3. 记录在 R/M 设置中至少 1 次先前全身治疗的治疗失败，除非确定不合适。
  4. 通过实体瘤反应评估标准 (RECIST) v1.1 可测量的疾病。
  5. 患有依赖于 HRAS 和/或 PIK3CA 的肿瘤。
  6. 东部肿瘤合作组织 (ECOG) 的表现状态为 0-1。
  7. 可接受的肝、肾、内分泌和血液学功能。
  8. 必须能够吞服 alpelisib 整片或含有压碎片剂的口服混悬液。 喂食管不得用于 alpelisib 给药。
  9. 其他协议定义的纳入标准可能适用。

排除标准：

  1. 经组织学证实的唾液腺、甲状腺、（原发性）皮肤鳞状或非鳞状组织学（例如粘膜黑色素瘤）。
  2. 正在接受某些抗癌药的持续治疗。
  3. 先前使用 FTI 或 PI3K、mTOR 或 AKT 抑制剂治疗（至少 1 个完整治疗周期）。
  4. 在过去 6 个月内接受过不稳定型心绞痛、心肌梗塞和/或脑血管病发作的治疗。
  5. 在第 1 周期第 1 天的 4 周内出现不可耐受的 2 级或≥ 3 级神经病变或不稳定神经系统症状的证据。
  6. 在第 1 周期第 1 天之前的 2 周内，未完全康复的大手术（诊断性手术除外）。
  7. 需要全身治疗的活动性、不受控制的细菌、病毒或真菌感染。
  8. 已确诊患有 1 型糖尿病或不受控制的 2 型糖尿病的参与者。
  9. 参与者有胃肠道 (GI) 功能受损或 GI 疾病，可能会根据研究者的判断显着改变试验药物的吸收。
  10. 参与者目前有肺炎/间质性肺病的记录。
  11. 参与者有严重皮肤反应史，例如史蒂文斯-约翰逊综合征 (SJS)、多形性红斑 (EM)、中毒性表皮坏死松解症 (TEN) 或伴有嗜酸性粒细胞增多和全身症状的药物反应 (DRESS)。
  12. 其他协议定义的排除标准可能适用。

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：非随机化
  • 介入模型：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：PIK3CA 依赖性（队列 1）
患有 R/M HNSCC 的成年参与者，其肿瘤含有 PI3KCA（激活）突变和/或扩增
药品：替比法尼
口服给药
药品：阿尔培利西
口服给药
其他名称：
  • BYL719
实验性的：HRAS 依赖性（队列 2）
患有 R/M HNSCC 的成年参与者，其肿瘤具有增加的 HRAS 依赖性，定义为 HRAS 过度表达
药品：替比法尼
口服给药
药品：阿尔培利西
口服给药
其他名称：
  • BYL719

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
Dose-limiting toxicity (DLT)
大体时间：First 28 days (1 cycle) of combination therapy
Rate of DLTs evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. A Treatment-Emergent Adverse Event (TEAE) is an AE occurring on or after Cycle 1 Day 1 and within 30 days of the last dose of tipifarnib or alpelisib, whichever is later. Patients with multiple events are counted only once at the highest CTCAE grade.
First 28 days (1 cycle) of combination therapy
Descriptive statistics of Adverse Events (AEs)
大体时间：From Cycle 1 Day 1 until 30 days after last trial intervention dose or 30 days after trial completion, whichever comes first, assessed up to 2 years
Descriptive statistics of Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs; AE severity will be assessed per the NCI CTCAE v 5.0. AEs are coded using the MedDRA dictionary version 28.0. A TEAE is an AE occurring on or after Cycle 1 Day 1 and within 30 days of the last dose of tipifarnib or alpelisib, whichever is later. At each level of summation (system organ class, preferred term), a patient reporting more than one adverse event is counted only once.
From Cycle 1 Day 1 until 30 days after last trial intervention dose or 30 days after trial completion, whichever comes first, assessed up to 2 years

次要结果测量

结果测量
措施说明
大体时间
疾病控制率 (DCR)
大体时间：从第1周期第1天开始，直至首次记录疾病进展、开始新的抗癌治疗或死亡（以先发生者为准），评估长达2年
疾病控制率（完全缓解 + 部分缓解 + 疾病稳定）
从第1周期第1天开始，直至首次记录疾病进展、开始新的抗癌治疗或死亡（以先发生者为准），评估长达2年
中位疾病控制持续时间
大体时间：从首次记录治疗反应到首次记录疾病进展、开始新的抗癌治疗或死亡（以先发生者为准），评估时间最长为2年
定义为：在确认达到客观缓解（CR/PR）的患者中，从首次记录缓解到首次通过RECIST v1.1标准记录疾病进展，或至因任何原因死亡（在开始新的抗癌治疗前），以先发生者为准的时间（以月计）。
从首次记录治疗反应到首次记录疾病进展、开始新的抗癌治疗或死亡（以先发生者为准），评估时间最长为2年
疾病稳定率
大体时间：从第1周期第1天起，直至首次记录疾病进展、开始新的抗癌治疗或死亡（以先发生者为准），评估时间最长可达2年
从第1周期第1天起，直至首次记录疾病进展、开始新的抗癌治疗或死亡（以先发生者为准），评估时间最长可达2年
疾病稳定期（SD）的中位持续时间
大体时间：从首次记录有应答起，直至首次记录疾病进展、开始新的抗癌治疗或死亡（以先发生者为准），评估时间最长为2年
根据RECIST v1.1标准定义为持久性SD（≥12周）
从首次记录有应答起，直至首次记录疾病进展、开始新的抗癌治疗或死亡（以先发生者为准），评估时间最长为2年
Objective Response Rate (ORR)
大体时间：From Cycle 1 Day 1 until first documentation of disease progression, the start of new anti-cancer therapy, or death, whichever occurs first, assessed up to 2 years
Defined as the proportion of participants with best overall response as a confirmed complete response (CR) or confirmed partial response (PR) by RECIST v1.1. Clopper-Pearson 95% confidence intervals are calculated based on binomial distribution.
From Cycle 1 Day 1 until first documentation of disease progression, the start of new anti-cancer therapy, or death, whichever occurs first, assessed up to 2 years
Median duration of response
大体时间：From first documentation of response to first documentation of disease progression, the start of new anti-cancer therapy, or death, whichever occurs first, assessed up to 2 years
Defined for participants with confirmed objective response as the time from the first documentation of response to the first documentation of disease progression by RECIST v1.1 or to death due to any cause before new anti-cancer treatment, whichever occurs first. Median is calculated using Kaplan-Meier method. Confidence interval for median is calculated using the Brookmeyer-Crowley method. Minimum and maximum are actual values rather than estimates.
From first documentation of response to first documentation of disease progression, the start of new anti-cancer therapy, or death, whichever occurs first, assessed up to 2 years
Cmax of tipifarnib and alpelisib when administered in combination
大体时间：Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.
Maximum observed concentration following single dose and multiple dose administration
Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.
Tmax of tipifarnib and alpelisib when administered in combination
大体时间：Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.
Time to reach maximum observed concentration following single dose and multiple dose administration
Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.
AUC(0-last) of tipifarnib and alpelisib when administered in combination
大体时间：Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.
Area under the concentration-time curve from time zero to time of last quantifiable concentration following single dose and multiple dose administration
Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.
AUC(tau) of tipifarnib and alpelisib when administered in combination
大体时间：Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.
Area under the concentration-time curve during a dosage interval following single dose and multiple dose administration
Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.
AUC(0-infinity) of tipifarnib and alpelisib when administered in combination
大体时间：Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.
Area under the concentration-time curve from time zero to infinity following single dose administration
Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.
CL/F of tipifarnib and alpelisib when administered in combination
大体时间：Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.
Apparent total clearance of the drug following single dose and multiple dose administration
Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.
Vd/F of tipifarnib and alpelisib when administered in combination
大体时间：Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.
Apparent volume of distribution following single dose and multiple dose administration
Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.
Half-life of tipifarnib and alpelisib when administered in combination
大体时间：Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.
Time required for the amount of drug in the body to decrease by half following single dose and multiple dose administration
Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.
Accumulation ratio of tipifarnib and alpelisib when administered in combination
大体时间：Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.
Defined as the ratio of drug exposure at steady state to exposure following a single dose. For tipifarnib, the accumulation ratio was calculated as the ratio of area under the plasma concentration-time curve over the dosing interval (AUCτ) on Cycle 2 Day 1 (C2D1) to AUC from time zero to 12 hours (AUC₀-12) on Cycle 1 Day 1 (C1D1). For alpelisib, the accumulation ratio was calculated as the ratio of AUCτ on C2D1 to AUC from time zero to 24 hours (AUC₀-24) on C1D1.
Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.
Progression-free survival (PFS)
大体时间：From Cycle 1 Day 1 until first documentation of disease progression, the start of new anti-cancer therapy, or death, whichever occurs first, assessed up to 3 years
Defined as the time in months from C1D1 to the first documentation of disease progression or death due to any cause before new anti-cancer treatment. Median is calculated using Kaplan-Meier method. Confidence interval for median is calculated using the Brookmeyer-Crowley method. Minimum and maximum are actual values rather than estimates.
From Cycle 1 Day 1 until first documentation of disease progression, the start of new anti-cancer therapy, or death, whichever occurs first, assessed up to 3 years
Proportion of participants with PFS at 6 months
大体时间：From Cycle 1 Day 1 until first documentation of disease progression, the start of new anti-cancer therapy, or death, whichever occurs first, assessed up to 6 months
Proportion of participants alive and without disease progression at 6 months and before new anti-cancer treatment. Survival probability and confidence interval are calculated based on Kaplan-Meier product-limit method and Greenwood's formula.
From Cycle 1 Day 1 until first documentation of disease progression, the start of new anti-cancer therapy, or death, whichever occurs first, assessed up to 6 months
Overall Survival (OS)
大体时间：From Cycle 1 Day 1 until 3 years of treatment or death from any cause, whichever comes first
OS is the time in months from C1D1 to the date of death due to any cause. For patients with no events, OS will be censored at the last known to be alive date. Median is calculated using Kaplan-Meier method. Confidence interval for median is calculated using the Brookmeyer-Crowley method. Minimum and maximum are actual values rather than estimates.
From Cycle 1 Day 1 until 3 years of treatment or death from any cause, whichever comes first
Proportion of patients with OS at 12 months
大体时间：From Cycle 1 Day 1 until 12 months of treatment or death from any cause, whichever comes first
Proportion of participants alive at 12 months. For patients with no events, OS will be censored at the last known to be alive date. Survival probability and confidence interval are calculated based on Kaplan-Meier product-limit method and Greenwood's formula.
From Cycle 1 Day 1 until 12 months of treatment or death from any cause, whichever comes first

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Kura Oncology, Inc.

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2021年12月7日

初级完成 (实际的)

2025年8月29日

研究完成 (实际的)

2025年8月29日

研究注册日期

首次提交

2021年7月27日

首先提交符合 QC 标准的

2021年8月5日

首次发布 (实际的)

2021年8月10日

研究记录更新

最后更新发布 (实际的)

2026年9月8日

上次提交的符合 QC 标准的更新

2026年8月25日

最后验证

2026年8月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • KO-TIP-013

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

在美国制造并从美国出口的产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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