TIGER-1: Safety and Efficacy Study of Rociletinib (CO-1686) or Erlotinib in Patients With EGFR-mutant/Metastatic NSCLC Who Have Not Had Any Previous EGFR Directed Therapy (EGFR)
2019年4月29日 更新者：Clovis Oncology, Inc.
TIGER 1: A Randomized, Open-Label, Phase 2/3 Study of CO-1686 or Erlotinib as First-Line Treatment of Patients With EGFR-Mutant Advanced/Metastatic NSCLC
The purpose of this study is to compare the safety and anti-tumor effect of rociletinib with erlotinib in patients whose tumors have specific EGFR mutations and who have not previously received any treatment for advanced/metastatic EGFR mutated NSCLC.
This study is a 'Randomized' Study.
This means that upon entering the study, patients will be randomly assigned to be dosed with either rociletinib twice a day or erlotinib once a day.
Patients will continue to take either rociletinib or erlotinib until it is no longer beneficial.
研究概览
详细说明
This is a randomized, Phase 2/3 study of rociletinib versus erlotinib as a first-line treatment for patients with EGFR-mutant advanced/metastatic NSCLC whose tumors have EGFR-activating mutations.
The study will consist of Phase 2 and Phase 3 parts which will use the same enrollment criteria and treatment assignment principles.
Patients will be randomized 1:1 to erlotinib or rociletinib.
The Phase 2 part is an open-label study.
In the Phase 3 part, the sponsor will be blinded to the efficacy and safety results.
The study will consist of a screening phase to establish study eligibility (including tumor genotype) and document baseline measurements, a treatment phase, in which patients will receive either rociletinib BID (twice a day) or erlotinib QD (once daily) to ascertain safety and efficacy until protocol-defined disease progression, and a follow-up phase, to monitor survival status and subsequent NSCLC cancer therapy.
In the Phase 2 part only, patients initially randomized to erlotinib may be eligible to participate in an optional crossover phase to receive rociletinib if they demonstrate the T790M resistance mutation after radiographic progression on erlotinib treatment among other eligibility requirements.
Patients eligible for this study must have EGFR-mutated NSCLC who have not been treated with an EGFR-directed therapy.Treatment with rociletinib or erlotinib is continuous.
Each 28 day period of treatment will represent one cycle, with dosing initiated on Cycle 1 Day 1 (C1 D1).
研究类型
介入性
注册 (实际的)
100
阶段
- 阶段2
- 第三阶段
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
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Taichung、台湾、40705
- Taichung Veterans General Hospital
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Taipei、台湾、11217
- Taipei Veterans General Hospital
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Taoyuan、台湾、33305
- Chang Gung Memorial Hospital Linkou
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Busan、大韩民国、602-715
- Dong-A University Hospital
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Incheon、大韩民国、400-711
- Inha University Hospital
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Seongnam-si、大韩民国、463-707
- Seoul National University Bundang Hospital
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Seoul、大韩民国、135-710
- Samsung Medical Center
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Seoul、大韩民国、138-736
- Asan Medical Center
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Seoul、大韩民国、120-752
- Severance Hospital, Yonsei University Health System
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Suwon、大韩民国、442-723
- The Catholic University of Korea Saint Vincent's Hospital
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Berlin、德国
- Evangelische Lungenklinik Berlin
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Bayern
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Gauting、Bayern、德国、82131
- Asklepios Fachkliniken München-Gauting
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Niedersachsen
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Oldenburg、Niedersachsen、德国、26121
- Pius Hospital Oldenburg
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Nordrhein-Westfalen
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Köln、Nordrhein-Westfalen、德国、50937
- Universitätsklinikum Köln
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Rheinland-Pfalz
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Mainz、Rheinland-Pfalz、德国、55131
- Katholisches Klinikum Mainz, Sankt Hildegardis-Krankenhaus
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Livorno、意大利、57124
- Ospedale Civile di Livorno
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Alabama
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Birmingham、Alabama、美国、35294
- University of Alabama at Birmingham
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California
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Burbank、California、美国、91505
- East Valley Hematology and Oncology Medical Group, Inc.
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Duarte、California、美国、91010
- City of Hope
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Fountain Valley、California、美国、92708
- Compassionate Cancer Care Medical Group, Inc.
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Fullerton、California、美国、92835-3825
- St. Joseph Heritage Healthcare
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La Jolla、California、美国、92093-0698
- UC San Diego Moores Cancer Center
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Los Angeles、California、美国、90089
- University of Southern California, Norris Comprehensive Cancer Center
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Sacramento、California、美国、95816
- Sutter Medical Group
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San Francisco、California、美国、94115
- University of California San Francisco
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Santa Barbara、California、美国、93105
- Sansum Clinic
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Santa Maria、California、美国、93454
- Central Coast Medical Oncology Corporation
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Santa Monica、California、美国、90404
- UCLA Medical Center
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Whittier、California、美国、90603
- The Oncology Institute of Hope and Innovation
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Colorado
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Aurora、Colorado、美国、80045
- University of Colorado Cancer Center
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District of Columbia
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Washington、District of Columbia、美国、20007
- Georgetown University Medical Center
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Florida
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Fleming Island、Florida、美国、32003
- Cancer Specialists of North Florida
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Fort Myers、Florida、美国、33916
- Florida Cancer Specialists and Research Institute
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Miami、Florida、美国、33176
- Advanced Medical Specialties
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Orlando、Florida、美国、32804
- Florida Hospital Cancer Institute
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Saint Petersburg、Florida、美国、33705
- Florida Cancer Specialists
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Weston、Florida、美国、33331
- Cleveland Clinic Florida
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Illinois
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Chicago、Illinois、美国、60611
- Northwestern University
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Chicago、Illinois、美国、60612
- University of Illinois Cancer Center
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Niles、Illinois、美国、60714
- Illinois Cancer Specialists
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Maryland
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Baltimore、Maryland、美国、21237
- Harry and Jeanette Weinberg Cancer Institute at Franklin Square
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Bethesda、Maryland、美国、20889
- Walter Reed Army Institute of Research
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Michigan
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Detroit、Michigan、美国、48201
- Barbara Ann Karmanos Cancer Institute
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Nebraska
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Omaha、Nebraska、美国、68130
- Oncology Hematology West PC
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Nevada
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Henderson、Nevada、美国、89014
- Comprehensive Cancer Centers of Nevada
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New Jersey
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East Brunswick、New Jersey、美国、08816
- Regional Cancer Care Associates, LLC
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Morristown、New Jersey、美国、07962
- Regional Cancer Care Associates
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New York
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Bronx、New York、美国、10461
- Montefiore Medical Center
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Buffalo、New York、美国、14263
- Roswell Park Cancer Institute
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North Carolina
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Durham、North Carolina、美国、27710
- Duke University Medical Center
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Ohio
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Cincinnati、Ohio、美国、45267
- University of Cincinnati Medical Center
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Cleveland、Ohio、美国、44195
- Cleveland Clinic
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Cleveland、Ohio、美国、44106
- University Hospitals Case Medical Center
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Oregon
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Portland、Oregon、美国、97239
- Oregon Health and Science University
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Pennsylvania
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Philadelphia、Pennsylvania、美国、19107
- Thomas Jefferson University Hospital
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South Carolina
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Charleston、South Carolina、美国、29425
- Hollings Cancer Center
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Tennessee
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Chattanooga、Tennessee、美国、37404
- Tennessee Oncology, PLLC
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Nashville、Tennessee、美国、37203
- Tennessee Oncology, PLLC
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Nashville、Tennessee、美国、37212-3505
- USC/Norris Comprehensive Cancer Center
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Texas
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Austin、Texas、美国、78745
- Texas Oncology, PA
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Beaumont、Texas、美国、77702
- Texas Oncology-Beaumont
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Bedford、Texas、美国、76022
- Texas Oncology, P.A.
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Dallas、Texas、美国、75390-8852
- University of Texas Southwestern Medical Center
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Houston、Texas、美国、77030
- Houston Methodist Cancer Center
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Houston、Texas、美国、77030
- The University of Texas - MD Anderson Cancer Center
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Plano、Texas、美国、75075-7753
- Texas Oncology-Plano East
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Virginia
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Fairfax、Virginia、美国、22031
- Virginia Cancer Specialists, PC
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Washington
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Seattle、Washington、美国、98109
- University of Washington
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Vancouver、Washington、美国、98684
- Northwest Cancer Specialists, P.C.
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Yakima、Washington、美国、98902
- Yakima Valley Memorial Hospital, North Star Lodge
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Barcelona、西班牙、08035
- Hospital Universitario Vall d'Hebron
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Madrid、西班牙、28034
- Hospital Universitario Ramon y Cajal
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Hong Kong、香港
- Queen Mary Hospital
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New Territories
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Hong Kong、New Territories、香港
- Prince of Wales Hospital
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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
有资格学习的性别
全部
描述
Inclusion Criteria:
- Histologically or cytologically confirmed metastatic or unresectable locally advanced/metastatic NSCLC
- Documented evidence of a tumor with activating EGFR mutations by local testing. Patients with exon 20 insertions are not eligible with the exception of patients with documented evidence of the exon 20 insertion A763_Y764insFQEA in the EGFR gene
- Have undergone a biopsy or surgical resection of either primary or metastatic tumor tissue within 60 days of the first day of study treatment, C1D1, and have tissue available to send to sponsor laboratories or are able to undergo a biopsy during screening and provide tissue to sponsor laboratories
- Measureable disease according to RECIST Version 1.1
- Life expectancy of at least 3 months
- ECOG (Eastern Cooperative Oncology Group) performance status of 0 to 1
- Minimum age 18 years (in certain territories, the minimum age requirement may be higher (e.g. 20 years in Japan and Taiwan)
- Adequate hematological and biological function, confirmed by defined laboratory values
- Written consent on an IRB/IEC-approved Informed Consent Form (ICF) prior to any study-specific evaluation
Exclusion Criteria:
- Documented evidence of an exon 20 insertion activating mutation other than A763_Y764insFQEA in the EGFR gene
- Prior treatment with cytotoxic chemotherapy for advanced NSCLC; neoadjuvant/adjuvant chemotherapy is permitted if at least 6 months has elapsed between the end of chemotherapy and randomization
- Active second malignancy; i.e., patient known to have potentially fatal cancer present for which he/she may be (but not necessarily) currently receiving treatment
- Patients with a history of malignancy that has been completely treated, and currently with no evidence of that cancer, are permitted to enroll in the trial provided all chemotherapy was completed > 6 months prior and/or bone marrow transplant > 2 years prior to first day of study treatment
- Known pre-existing interstitial lung disease
- Brain metastases
- Treatment with prohibited medications less than or equal to 14 days prior to first day of study treatment
- Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval if that treatment cannot be either discontinued or switched to a different medication prior to administration of study drug
- Prior treatment with EGFR TKIs (e.g. erlotinib, gefitinib, neratinib, afatinib, AZD9291, or dacomitinib), rociletinib or other drugs that target mutant EGFR
- Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTCF) > 450 ms
- Inability to measure QT interval on ECG
- Personal or family history of long QT syndrome
- Implantable pacemaker or implantable cardioverter defibrillator
- Resting bradycardia < 55 beats/min
- Non-study related surgical procedures less than or equal to 7 days prior to administration of study drug. In all cases, the patient must be sufficiently recovered and stable before treatment administration.
- Females who are pregnant or breastfeeding
- Refusal to use adequate contraception for fertile patients (females and males) for 12 weeks after the last dose of rociletinib and 2 weeks after the last dose of erlotinib
- Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study
- Any other reason the investigator considers the patient should not participate in the study
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：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 |
|---|---|
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有源比较器：Erlotinib Mono-Therapy
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Erlotinib will be administered once a day
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实验性的：Rociletinib Mono-Therapy
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Rociletinib will be administered twice daily
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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 |
|---|---|---|
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Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS)
大体时间：Cycle 1 Day 1 to End of Treatment, up to approximately 35 months
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To compare the antitumor efficacy of oral single-agent rociletinib with that of erlotinib as measured by progression-free survival (PFS), when administered as a first-line targeted treatment to patients with EGFR-mutated, advanced NSCLC.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of one or more new lesions is also considered progression.
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Cycle 1 Day 1 to End of Treatment, up to approximately 35 months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Confirmed Response Rate
大体时间：Cycle 1 Day 1 to End of Treatment, up to approximately 35 months.
|
Proportion of patients with a best overall confirmed response of partial response (PR) or complete response (CR) recorded from the start of the treatment until disease progression or recurrence. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR),at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Overall Response (OR),is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment was dependent on the achievement of both measurement and confirmation criteria. |
Cycle 1 Day 1 to End of Treatment, up to approximately 35 months.
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Duration of Response
大体时间：Cycle 1 Day 1 to End of Treatment, up to approximately 35 months
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Duration of Response in Patients with Confirmed Response per Investigator
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Cycle 1 Day 1 to End of Treatment, up to approximately 35 months
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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。
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
2014年11月1日
初级完成 (实际的)
2017年6月28日
研究完成 (实际的)
2017年6月28日
研究注册日期
首次提交
2014年6月30日
首先提交符合 QC 标准的
2014年7月7日
首次发布 (估计)
2014年7月10日
研究记录更新
最后更新发布 (实际的)
2019年5月7日
上次提交的符合 QC 标准的更新
2019年4月29日
最后验证
2019年4月1日
更多信息
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.