Clinical trial NCT04187352: A Study of CS1001 in Subjects With Esophageal Squamous Cell Carcinoma
Official title: A Multi-Center, Double-Blind, Randomized, Phase III Study to Investigate the Efficacy and Safety of CS1001 in Combination With Fluorouracil and Cisplatin (FP) Compared to Placebo in Combination With FP as First-Line Therapy in Subjects With Unresectable Locally Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma (ESCC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Unresectable Locally Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma
Lead sponsor: CStone Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-12-05
Enrollment: 540
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: Phase III Study to Investigate the Efficacy and Safety of CS1001 or Placebo in Combination with FP as First-Line Therapy in Subjects with Unresectable Locally Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma


Eligibility criteria: Inclusion criteria

1. ≥ 18 years and ≤ 75 years on the day of signing informed consent form (ICF).
2. Fully informed of the study, with good compliance and willing to provide written ICF. The ICF must be signed before performing any protocol-related procedure (that is not a part of subject's routine medical care).
3. Subjects with pathohistologically or cytologically confirmed unresectable locally advanced, relapsed or metastatic ESCC (based on American Joint Committee on Cancer \[AJCC\] Guideline version 8, see Appendix 14.2)
4. Subjects must not be eligible for radical therapy such as radical chemoradiotherapy or surgery.
5. Subjects who have not received any systemic anti-neoplastic therapy as the main regimen for locally advanced or metastatic ESCC. (Subjects who received prior neoadjuvant, adjuvant or radical chemoradiotherapy for ESCC but had relapse or progression of disease 6 months after the completion of these treatments are allowed.)
6. ECOG PS 0 or 1.
7. Life expectancy ≥ 3 months.
8. Subjects have at least one measurable lesion as evaluated by the investigator according to RECIST v1.1, and the baseline imaging assessment must be performed within 28 days prior to the first dose of investigational product. Target lesions in the past radiation fields, if confirmed as radiological progression, are considered as measurable lesions.
9. Palliative treatment (e.g. radiotherapy) for local lesion must be completed ≥ 14 days prior to the first dose of investigational product.
10. Subjects must provide tumor tissue samples (formalin fixed-paraffin embedded \[FFPE\] tissue block or unstained tumor tissue sections) for biomarker analysis, in order to determine the expression of PD-L1.
11. Subjects must have adequate organ function as assessed in the following laboratory tests (subjects must not receive any blood transfusion or any hematopoietic growth factor within 7 days prior to the test)
12. Female subjects with childbearing potential (unless with documentation of sterilization surgery or being post-menopausal) must have negative serum pregnancy test result at screening. Female subject with childbearing potential (unless with documentation of sterilization surgery or being post-menopausal) or male subjects and their partners must agree to use an effective contraceptive measure from the day of signing ICF till at least 6 months after the last dose of investigational product.

Exclusion criteria

1. Adenocarcinoma, mixture of adenocarcinoma and squamous cell carcinoma, or other pathological type of esophageal cancer.
2. Subjects with active central nervous system (CNS) metastasis and/or carcinomatous meningitis (that is symptomatic, or requires treatment, or no radiological evidence confirming the stability of the lesion within 28 days prior to the first dose of investigational product).
3. With another active primary malignancy in the past 5 years, except local curable cancers that have undergone curative therapy, e.g. basal cell carcinoma of skin, squamous cell carcinoma of skin, superficial bladder cancer, prostate cancer in situ, breast cancer in situ or cervical cancer in situ.
4. Known history of positive human immunodeficiency virus (HIV) test result or acquired immunodeficiency syndrome (AIDS).
5. Any severe or uncontrolled systemic disease, e.g., diabetes mellitus or hypertension, that may increase the risk associated with participation in the study or investigational product administration, or compromise subject's ability to receive investigational product, as per investigator's judgment.
6. Subjects who have previously received any treatment of antibody or drug that targets at T-cell coregulatory pathways or immune checkpoint pathways, e.g., antibodies targeting at programmed death receptor-1 (PD-1), programmed death receptor-ligand 1 (PD-L1), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), OX-40, CD137, T cell immunoglobulin mucin molecule 3 (TIM-3), lymphocyte activation gene 3 (LAG-3), etc. Subjects who have received cell-based immunotherapy (e.g., cytokine-induced killer cell \[CIK\], chimeric antigen receptor T cell \[CAR-T\] immunotherapy, etc.).
7. All toxicities except for alopecia and fatigue that are caused by the prior anti-neoplastic treatment has recovered to Grade 1 (according to National Cancer Institute Common Toxicity Criteria for Adverse Events \[NCI CTCAE\] v5.0).
8. Subjects with history of allogenic stem cell or solid organ transplantation.
9. Subjects with any condition that in the investigator's opinion are not suitable for participating in this study.

Primary outcomes:
measure: Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
timeFrame: Approximately 43 months from the time of randomization
measure: Overall survival (OS)
timeFrame: Approximately 43 months from the time of randomization
Secondary outcomes:
measure: PFS assessed by investigators according to RECIST v1.1
timeFrame: Approximately 43 months from the time of randomization
measure: Objective response rate (ORR) assessed by BICR and investigators according to RECIST v1.1
timeFrame: Approximately 43 months from the time of randomization
measure: Duration of response (DoR) assessed by BICR and investigators according to RECIST v1.1
timeFrame: Approximately 43 months from the time of randomization
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Hefei
country: China
facility: Hefei Second People's Hospital
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Hefei
country: China
facility: The Second Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Tsinghua Changgung Hospital
state: Beijing
city: Beijing
country: China
facility: Peaking University International Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing General Hospital
state: Chongqing
city: Chongqing
country: China
facility: Special Medical Center of The People's Liberation Army of China
state: Chongqing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Foshan
country: China
facility: The First People's Hospital of Foshan
state: Guangdong
city: Guangzhou
country: China
facility: Cancer Center of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial Hospital of Traditional Chinese Medicine
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Jiangmen
country: China
facility: Jiangmen Central Hospital
state: Guangdong
city: Jieyang
country: China
facility: Jieyang People's Hospital
state: Guangdong
city: Shantou
country: China
facility: Affiliated Tumor Hospital of Shantou University Medical College
state: Guangdong
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital of Sun Yat sen University
state: Guangdong
city: Nanning
country: China
facility: Guangxi Medical University Affiliated Tumor Hospital
state: Guangxi
city: Haikou
country: China
facility: Hainan General Hospital
state: Hainan
city: Haikou
country: China
facility: The Second Affiliated Hospital of Hainan Medical University
state: Hainan
city: Chengde
country: China
facility: Affiliated Hospital of Chengde Medical University
state: Hebei
city: Handan
country: China
facility: Handan Central Hospital
state: Hebei
city: Shijiazhuang
country: China
facility: Shijiazhuang People's Hospital
state: Hebei
city: Haerbin
country: China
facility: The Affiliated Tumor Hospital of Harbin Meidical University
state: Heilongjiang
city: Anyang
country: China
facility: Anyang Cancer Hospital
state: Henan
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Nanyang
country: China
facility: Nanyang Central Hospital
state: Henan
city: Nanyang
country: China
facility: Nanyang First People's Hospital
state: Henan
city: Puyang
country: China
facility: Puyang Oilfield General Hospital
state: Henan
city: Xinxiang
country: China
facility: Xinxiang First People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Wuhan
country: China
facility: Tongji Medical College of HUST, Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Wuhan Fifth Hospital
state: Hubei
city: Wuhan
country: China
facility: Wuhan Union Hospital
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changzhou
country: China
facility: Changzhou Tumor Hospital
state: Jiangsu
city: Huai'an
country: China
facility: Huai'an First People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
state: Jiangxi
city: Nanchang
country: China
facility: The First Affiliated Hospital Of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Changchun
country: China
facility: The Second Hospital of Jilin University
state: Jilin
city: Tonghua
country: China
facility: Tonghua Central Hospital
state: Jilin
city: Shenyang
country: China
facility: Liaoning Cancer Hospital and Institute
state: Liaoning
city: Jinan
country: China
facility: Jinan central Hospital
state: Shandong
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi Cancer Hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Chest Hospital
state: Shanghai
city: Linfen
country: China
facility: Linfen Central Hospital
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi Provincial Cancer Hospital
state: Shanxi
city: Chengdu
country: China
facility: Chengdu Fifith people's hospital
state: Sichuan
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital Sichuan University
state: Sichuan
city: Luzhou
country: China
facility: The Affiliated Hospital of Southwest Medical University
state: Sichuan
city: Suining
country: China
facility: Suining Central Hospital
state: Sichuan
city: Yibin
country: China
facility: Yibin Second People's Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Urumqi
country: China
facility: Cancer Hospital Affiliated to Xinjiang Medical University
state: Xinjiang
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
Study officials:
References: