Clinical trial NCT03581786: The Efficacy and Safety Study of TORIPALIMAB INJECTION Combined With Chemotherapy for Nasophapyngeal Cancer
Official title: A Phase III, Randomized, Placebo Controlled, Multicenter, Double-Blind Study Comparing Toripalimab Injection (JS001) Combined With Chemotherapy Versus Placebo Combined With Chemotherapy for Recurrent or Metastatic Nasopharyngeal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Recurrent or Metastatic NPC
Lead sponsor: Shanghai Junshi Bioscience Co., Ltd.
Sponsor class: OTHER
First posted: 2018-07-10
Enrollment: 289
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, placebo-controlled, multi-center, double blinded, Phase III study to determine the efficacy and safety of TORIPALIMAB INJECTIO（JS001） in combination with gemcitabine/cisplatin compared with placebo in combination with gemcitabine/cisplatin as first-line treatment in patients with histological/cytological confirmation of recurrent or metastatic NPC. The primary endpoint is PFS in all patients. Approximately 280 patients who fulfill all of the inclusion criteria and none of the exclusion criteria will be randomized in a 1:1 ratio to one of the two treatment arms. patients will be randomly assigned to the combination of JS001 (Arm A) or placebo (Arm B) with gemcitabine and cisplatin given every 3 weeks (Q3W) in 3-week cycles.

Detailed description: Total 289 patients were enrolled and randomized in a 1:1 ratio to the group of JS001 (Arm A) with gemcitabine and cisplatin or placebo (Arm B) with gemcitabine and cisplatin every 3 weeks (Q3W) in the 'during chemotherapy' phase. During the 'post-chemotherapy' phase, patients randomized to Arm A or Arm B will continue treatment with JS001 or placebo as maintenance therapy Q3W until excessive toxicity or progressive disease, withdrawal of consent or Investigator's judgement or a maximum of 2 years. Tumor evaluation scans will be performed at screening (as baseline) then every 6weeks in the first 12 months then every 9 weeks thereafter until objective disease progression. The primary objective is to compare PFS as assessed by the IRC in ITT population (all randomized patients).

Eligibility criteria: Inclusion Criteria:

* 1. Age ≥ 18 years and ≤75 years.
* 2. Histological/cytological confirmation of NPC.
* 3. Primarily metastatic (stage IVB as defined by the International Union against Cancer and American Joint Committee on Cancer staging system for NPC, eighth edition) or recurrent NPC that is not amenable for local regional treatment or curative treatment.
* 4. At least 1 measurable lesion according to RECIST version 1.1.
* 5. Life expectancy ≥ 3 months

Exclusion Criteria:

* 1. History of severe hypersensitivity reactions to other mAbs or any ingredient of JS001.
* 2. Prior therapy targeting PD-1 receptor, or its ligand PD-L1, or cytotoxic T lymphocyte associated protein 4 (CTLA4) receptor.
* 3. Major surgical procedure other than for diagnosis of NPC within 28 days prior to randomization or anticipation of need for a major surgical procedure during the study
* 4. History of hypersensitivity to gemcitabine or cisplatin or to any of the excipients.
* 5. Female patients who are at pregnancy or lactation.

Primary outcomes:
measure: IRC-assessed Progression-Free Survival (PFS) According to RECIST v1.1
timeFrame: up to 2 years
Secondary outcomes:
measure: OS
timeFrame: up to 5 years
measure: Investigator-assessed ORR According to RECIST v1.1
timeFrame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
measure: Investigator-assessed DoR According to RECIST v1.1
timeFrame: From date of response until progressive disease. Up to 2 approximately years
measure: Investigator-assessed DCR According to RECIST v1.1
timeFrame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
measure: Investigator-assessed PFS According to RECIST v1.1
timeFrame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
measure: Investigator-assessed PFS Rate at 1 and 2 Years
timeFrame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
measure: OS Rate at 1 and 2 Years
timeFrame: From date of randomization until death, loss to follow-up, or study termination by the Sponsor whichever occurs first.Up to 3.5 approximately years
measure: Patient-Reported Outcome (PRO) Using EORTC QLQ-C30, EORTC QLQ-H&N35 and ECOG Performance Status Assessments
timeFrame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
measure: IRC-assessed ORR According to RECIST v1.1
timeFrame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
measure: IRC-assessed DoR According to RECIST v1.1
timeFrame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
measure: IRC-assessed DCR According to RECIST v1.1
timeFrame: From date of consent informed until 60 days after the last investigational product administration. Up to 2 approximately years
measure: Safety Variables Will be Monitored and Reported:AE.SAE.Vital Signs,Physical Examinations,Laboratory Variable,ECG
timeFrame: From date of consent informed until 60 days after the last investigational product administration. Up to 2 approximately years
measure: ADAs
timeFrame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
measure: PFS Assessed Per irRECIST
timeFrame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
measure: ORR Assessed Per irRECIST
timeFrame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
measure: DoR Assessed Per irRECIST
timeFrame: From date of response until progressive disease. Up to 2 approximately years
measure: DCR Assessed Per irRECIST
timeFrame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
state: Guangdong
city: Liuzhou
country: China
facility: Liuzhou Worker's Hospital
state: Guangxi
city: Nanning
country: China
facility: The People's Hospital of Guangxi Zhuang Autonomous Region
state: Guangxi
city: Shantou
country: China
facility: Cancer Hospital of Shantou University Medical College
state: Guangzhou
city: Zhanjiang
country: China
facility: Affiliated Hospital of Guangdong Medical University
state: Guangzhou
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital Sun Yat-Sen University - Medical Oncology
state: Guangzhou
city: Guiyang
country: China
facility: Guizhou Cancer Hospital_Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Haikou
country: China
facility: Hainan General Hospital (Hainan Province People's Hospital)
state: Hainan
city: Shijiazhuang
country: China
facility: Hebei Oncology Hospital
state: Hebei
city: Wuhan
country: China
facility: Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & TechnologyTongji Hospital
state: Hubei
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Oncology Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
state: Jiangxi
city: Shanghai
country: China
facility: Fudan University Cancer Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai first people's hospital
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Singapore
country: Singapore
facility: National Cancer Centre
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
city: Taichung City
country: Taiwan
facility: China Medical University Hospital
city: Taichung City
country: Taiwan
facility: TaiChung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital
Study officials:
affiliation: Sun Yat-sen University
name: Ruihua Xu, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mai HQ, Chen QY, Chen D, Hu C, Yang K, Wen J, Li J, Shi YR, Jin F, Xu R, Pan J, Qu S, Li P, Hu C, Liu YC, Jiang Y, He X, Wang HM, Lim WT, Liao W, He X, Chen X, Liu Z, Yuan X, Li Q, Lin X, Jing S, Chen Y, Lu Y, Hsieh CY, Yang MH, Yen CJ, Samol J, Feng H, Yao S, Keegan P, Xu RH. Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial. Nat Med. 2021 Sep;27(9):1536-1543. doi: 10.1038/s41591-021-01444-0. Epub 2021 Aug 2.