Clinical trial NCT04447118: Phase 3 Study of Pyrotinib Versus Docetaxel in Patients With Advanced Non-squamous NSCLC Harboring a HER2 Exon 20 Mutation Who Failed Platinum Based Chemotherapy
Official title: A Phase 3, Randomized, Open-label, Multicenter Study of the Efficacy and Safety of Pyrotinib Versus Docetaxel in Patients With Advanced Non-squamous Non-small Cell Lung Cancer (NSCLC) Harboring a HER2 Exon 20 Mutation Who Progressed on or After Treatment With Platinum Based Chemotherapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Non-squamous NSCLC
HER2 Exon 20 Mutation
Keywords: pyrotinib
docetaxel
HER2 Exon 20 Mutation
NSCLC
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-06-25
Enrollment: 151
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, positive-controlled, open-label, international multicenter, Phase 3 clinical study to compare the efficacy and safety of pyrotinib versus docetaxel in patients with advanced non-squamous NSCLC harboring a HER2 exon 20 mutation who failed platinum based chemotherapy.

Detailed description: 150 eligible subjects will be randomized in a 2:1 ratio (Study treatment Arm: Control Arm = 100 : 50 subjects) to receive pyrotinib or docetaxel monotherapy.

Each treatment cycle is defined as 21 days for subjects in both arms. Treatment regimen of pyrotinib (Study treatment Arm): 400 mg/d (QD) oral pyrotinib will be administered within 30 minutes after completion of a meal.

Treatment regimen of docetaxel (Control Arm): 75 mg/m2 (Q3W) of docetaxel will be administered via intravenous infusion.

In this study, crossover treatment is allowed for subjects in Control Arm. Within the specified time window of each cycle, subjects should complete physical examinations, laboratory tests, quality of life questionnaires and other tests to assess the safety and quality of life of the subjects.

During study treatment, tumor radiological assessments will be performed every 6 weeks (42 ± 7 days) in the first 52 weeks and every 12 weeks (84 ± 7 days) thereafter.

After the end of treatment and safety follow-up, all subjects will be followed for survival (every 56 ± 7 days) until death, withdrawal of informed consent, lost to follow-up, or termination of the study (whichever occurs first).

Eligibility criteria: Inclusion Criteria:

* Signed and dated written informed consent which is approved by IRB/EC, willing and able to comply with scheduled treatment, all examinations at study visits, and other study procedures.
* ECOG PS 0-1.
* Have histologically or cytologically confirmed locally advanced or metastatic non-squamous NSCLC disease.
* Before enrollment, a documented confirmed presence of activating mutations in exon 20 of the HER2 gene must be provided. Sufficient tumor tissue samples should be provided to retrospectively confirm the mutation status of the HER2 gene.
* Must have measureable disease per RECIST v1.1.
* For advanced NSCLC, patients must have had progressive disease on or after a platinum based chemotherapy, with or without immune checkpoint inhibitors (PD-1/PD-L1 inhibitors) and/or anti-angiogenic drugs. No more than 2 prior lines of systemic therapy are allowed.
* The laboratory test values must meet the following standards to manifest that the functional level of important organs/systems meets the requirements.
* Female patient of childbearing potential (WOCBP) and male patient whose - partner is WOCBP must agree to use effective contraception method during the study period.

Exclusion Criteria:

* Malignant tumors with other pathological types.
* Medical history of other active malignancies within last 5 years.
* Subjects with active CNS metastases.
* Previously treated with targeted drugs for HER2 gene mutations,or previously treated with docetaxel.
* Prior to the first dose of study treatment, patients with severe effusions with clinical symptoms, severe cardiac disease, or severe infection.
* Prior to the first dose of study treatment, patients with diseases or special conditions that affect drug administration and absorption.
* Congenital or acquired immunodeficiency.
* History of allergy to the study drugs or components.
* Prior to the first dose of study treatment, or during the study period, patients receive or are anticipated to receive continuous strong CYP3A4 inducers or inhibitors, P-gp inhibitors, or medications that are known to cause QT/QTc prolongation.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 26 months
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 36 months
measure: Objective response rate (ORR)
timeFrame: 26 months
measure: Disease control rate (DCR)
timeFrame: 26 months
measure: Duration of response (DoR)
timeFrame: 26 months
measure: Time to tumor progression (TTP)
timeFrame: 26 months
measure: Progression-free survival 2(PFS2)
timeFrame: 36 months
measure: Patient reported outcome (PRO) using EORTC QLQ-C30
timeFrame: 26 months
measure: Patient reported outcomes (PRO) using the QLQ-LC13
timeFrame: 26 months
measure: Plasma concentrations of pyrotinib
timeFrame: 26 months
measure: AEs and SAEs
timeFrame: 26 months
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California - Irvine Medical Center
state: California
city: Sacramento
country: United States
facility: University of California (UC) Davis Comprehensive Cancer Center
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialists South Divisio
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists North Divisio
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center (KUMC)
state: Kansas
city: New York
country: United States
facility: David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
state: New York
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Spokane
country: United States
facility: Summit Cancer Centers - North Spokane
state: Washington
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: Saint Leonards
city: Albury
country: Australia
facility: Border Medical Oncology
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
city: North Adelaide
country: Australia
facility: Calvary North Adelaide Hospital
city: Edegem
country: Belgium
facility: Antwerp University Hospital (UZA)
city: Gent
country: Belgium
facility: University Hospital Gent
city: Leuven
country: Belgium
facility: University Hospital (UZ) Leuven
city: Hefei
country: China
facility: the Second Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: beijing chest hospital,Capital medical university
state: Beijing
city: Beijing
country: China
facility: Peking university Cancer Hospital
state: Beijing
city: Chongqing
country: China
facility: The second affiliated hospital of ChongQing medical university
state: Chongqing
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangdong Pharmaceutical University
state: Guangdong
city: Cangzhou
country: China
facility: Cangzhou Hospital of Integrated Tcm-Wm.Hebei
state: Hebei
city: Ha'erbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: First Affiliated Hospital of ZhengzhouUniversity
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Hubei cancer hospital WardII
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
city: Yangzhou
country: China
facility: Subei People's Hospital of Jiangsu Province
state: Jiangsu
city: Nanchang
country: China
facility: The Second Affiliated of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Hohhot
country: China
facility: The affiliated hospital of inner mongolia medical univerity
state: Neimenggu
city: Jinan
country: China
facility: Shandong Cancer Hospital Affiliated to Shandong University
state: Shandong
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital, Tongji University
state: Shanghai
city: Shanghai
country: China
facility: Fudan University Cancer hospital
state: Shanghai
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Chest Hospital
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Provincial Cancer Hospital
state: Shanxi
city: Chengdu
country: China
facility: SiChuan Cancer Hospital
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital,Sichuan University
state: Sichuan
city: Yibin
country: China
facility: The Second People's Hosipital of Yibin
state: Sichuan
city: Tianjin
country: China
facility: General Hospital of Tianjin Medical University
state: Tianjin
city: Kunming
country: China
facility: Yunnan Provincial Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital ZheJiang University School Of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: The First Affiliated Hospital，ZheJiang University
state: Zhejiang
city: Hangzhou
country: China
facility: ZheJiang Cancer Hospital
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
state: Zhejiang
city: CAEN cedex 05
country: France
facility: Centre Francois Baclesse
city: Creteil
country: France
facility: Centre Hospitalier Intercommunal Creteil
city: Marseille cedex 20
country: France
facility: AP-HM - Hôpital Nord
city: Paris
country: France
facility: Hopital Bichat - Claude Bernard - AP-HP
city: Strasbourg Cedex
country: France
facility: CHRU Strasbourg
city: Toulouse
country: France
facility: CHU Toulouse - Hopital Larrey
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus Dresden
city: Giessen
country: Germany
facility: Uniklinikum Giessen und Marburg
city: Kempten
country: Germany
facility: Klinikverbund Kempten-Oberallgäu gGmbH
city: Leipzig
country: Germany
facility: POIS Leipzig GbR
city: Oldenburg
country: Germany
facility: Pius-Hospital Oldenburg, Centre of Radiotherapy and Medical Oncology, Dept. Medical Oncology
city: Aviano
country: Italy
facility: Centro Riferimento Oncologico - Aviano
city: Catania
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico G. Rodolico-San Marco - Presidio Ospedaliero G. Rodolico
city: Meldola (fc)
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Varese
country: Italy
facility: ASST dei Sette Laghi-Ospedale di Circolo e Fondazione Macchi di Varese
city: Seoul
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Bundang
city: Gyeonggi-do
country: Korea, Republic of
facility: Ajou University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital, The Catholic University of Korea
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Konin
country: Poland
facility: Centrum Onkologii KOMED
city: Lodz
country: Poland
facility: Salve-Medica
city: Lublin
country: Poland
facility: Instytut Genetyki i Immunologii GENIM
city: Poznan
country: Poland
facility: Med Polonia Sp. z o.o.
city: St. Petersburg
country: Russian Federation
facility: Petrov National Medical Research Center of Oncology
state: Saint Petersburg
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Clinical Oncological Dispensary
city: Moscow
country: Russian Federation
facility: JSC Group of companies Medsi
city: Saint Petersburg
country: Russian Federation
facility: Clinical hospital RZD-Medicine of St. Petersburg
city: Saint Petersburg
country: Russian Federation
facility: Eurocityclinic LLC
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology)
city: Barcelona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Badalona
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
state: Badalona
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Madrid
country: Spain
facility: Hospital Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan City
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital (CGMHLK)
city: Adana
country: Turkey
facility: Baskent University Adana Application and Research Center
city: Ankara
country: Turkey
facility: Ankara Sehir Hastanesi
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Medical Faculty
city: Izmir
country: Turkey
facility: Izmir Medical Park Hospital
city: Keçiören
country: Turkey
facility: Gulhane Training and Research Hospital
city: Konya
country: Turkey
facility: Necmettin Erbakan University Selcuklu Faculty of Medicine
city: Merkez
country: Turkey
facility: Trakya University Medical Faculty
Study officials:
affiliation: Jiangsu Hengrui Pharmaceutical Co., Ltd.
name: Wei Shi, MD,PhD
role: STUDY_DIRECTOR
References: