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A Phase II Study of SHR-1210 vs Placebo as Consolidation Chemotherapy After Radical Concurrent Chemoradiotherapy in Locally Advanced ESCC

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ClinicalTrials.gov Identifier: NCT03817658
Recruitment Status : Not yet recruiting
First Posted : January 25, 2019
Last Update Posted : January 25, 2019
Sponsor:
Collaborator:
Jiangsu HengRui Medicine Co., Ltd.
Information provided by (Responsible Party):
Feng Wang, The First Affiliated Hospital of Zhengzhou University

Brief Summary:
The purpose of this study is to observe and evaluate the efficacy and safety of SHR-1210 vs placebo as consolidation chemotherapy after radical concurrent chemoradiotherapy for unresectable locally advanced ESCC.

Condition or disease Intervention/treatment Phase
Esophageal Squamous Cell Carcinoma Drug: SHR-1210 Drug: Placebo Phase 2

Detailed Description:
In China, the incidence of esophageal cancer has declined in recent years, but the mortality rate has been ranked fourth. Morbidity and mortality were ranked sixth and fourth in all malignancies, respectively. Therefore, esophageal cancer has always been a major malignant tumor that threatens the health of our residents. We designed a multicenter, randomized, double-blind, open-label phase II clinical trial of anti-PD-1 antibody SHR-1210 versus placebo as consolidation chemotherapy (CCT) after radical concurrent chemoradiotherapy for unresectable locally advanced esophageal squamous cell carcinoma (ESCC).The purpose of this study is to observe and evaluate the efficacy and safety of SHR-1210 vs placebo as consolidation chemotherapy after radical concurrent chemoradiotherapy for unresectable locally advanced ESCC.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 725 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Clinical Trial of Anti-PD-1 Antibody SHR-1210 Versus Placebo as Consolidation Chemotherapy After Radical Concurrent Chemoradiotherapy in Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : October 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: SHR-1210
SHR-1210
Drug: SHR-1210

First stage:

Concurrent chemoradiotherapy:

Cisplatin:25-30mg/m2 ivgtt d1;Capecitabine:800mg/m2, bid d1-5,qw,5weeks;Synchronous radiotherapy:1.8-2Gy/d,5d/W,45-50Gy。 Consolidation treatment: Cisplatin: 60-75mg/m2 ivgtt d1 Capecitabine:1000mg/m2, bid d1-14,q3w 6weeks。

Second stage:

SHR-1210 was administered intravenously (no prophylactic use), a fixed dose of 200 mg, and 3 mg/kg for subjects with a baseline weight <50 kg. Each infusion for 30 min (not less than 20 min, no more than 60 min), once every 2 weeks, 1 cycle every 4 weeks, the cumulative longest medication period is 12 months.


Placebo Comparator: placebo
placebo
Drug: Placebo

First stage:

Concurrent chemoradiotherapy:

Cisplatin:25-30mg/m2 ivgtt d1;Capecitabine:800mg/m2, bid d1-5,qw,5weeks;Synchronous radiotherapy:1.8-2Gy/d,5d/W,45-50Gy。 Consolidation treatment: Cisplatin: 60-75mg/m2 ivgtt d1 Capecitabine:1000mg/m2, bid d1-14,q3w 6weeks。

Second stage:

Placebo was administered intravenously (no prophylactic use), a fixed dose of 200 mg, and 3 mg/kg for subjects with a baseline weight <50 kg. Each infusion for 30 min (not less than 20 min, no more than 60 min), once every 2 weeks, 1 cycle every 4 weeks, the cumulative longest medication period is 12 months.





Primary Outcome Measures :
  1. PFS [ Time Frame: up to 2 year ]
    Evaluation of anti-PD-1 antibody SHR-1210 for progression-free survival in patients with locally advanced esophageal squamous cell carcinoma who did not develop disease after concurrent chemoradiotherapy

  2. OS [ Time Frame: up to 2 year ]
    From date of randomization until the date of death from any cause


Secondary Outcome Measures :
  1. ORR [ Time Frame: up to 2 year ]
    Evaluation of the objective response rate of anti-PD-1 antibody SHR-1210 versus placebo in patients with locally advanced esophageal squamous cell carcinoma who had no disease progression after concurrent chemoradiotherapy(RECIST 1.1)

  2. DOR [ Time Frame: up to 2 year ]
    defined as the time from the first determination of an objective response until the first documentation of progression assessed by BIRC per RECIST v1.1 or death, whichever comes first

  3. Health-Related Quality of Life (HRQoL) [ Time Frame: up to 2 year ]
    assessment of the patient's overall health status using European Quality of Life-Core 30 Questionnaire index (EORTC QLQ-C30).

  4. Health-Related Quality of Life (HRQoL) [ Time Frame: up to 2 year ]
    assessment of the patient's overall health status using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire esophageal cancer specific module (EORTC QLQ-OES18).

  5. Health-Related Quality of Life (HRQoL) [ Time Frame: up to 2 year ]
    assessment of the patient's overall health status using the generic health state instrument European Quality of Life- 5 Dimensions (EuroQol 5D EQ-5D-5L).

  6. The incidence and severity of adverse events (AEs) [ Time Frame: up to 2 year ]
    according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18-75 years old, both men and women;
  2. Histology confirmed as esophageal squamous cell carcinoma;
  3. T1bN+M0, T2N0-2M0 local progress period;
  4. According to RECIST 1.1, at least one measurable lesion;
  5. Tissue samples shall be provided for biomarker analysis, preferably newly acquired tissues, and patients who are unable to provide newly acquired tissues may provide 5-8 pieces of 5um thick paraffin sections that are archived and preserved;
  6. ECOG: 0~1;
  7. Expected survival period ≥ 12 weeks;
  8. The main organs function normally, that is, the following criteria are met:

(1) Blood routine examination:

  1. HB≥90g/L;
  2. ANC ≥ 1.5 × 109 / L;
  3. PLT ≥ 80 × 109 / L; (2) Biochemical examination:

a. ALB ≥ 30g / L; b. ALT and AST ≤ 2.5ULN; if there is liver metastasis, ALT and AST ≤ 5ULN; c. TBIL ≤ 1.5ULN; d. plasma Cr ≤ 1.5ULN or creatinine clearance (CCr) ≥ 60ml / min; 9. Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ normal low limit (50%); 10. Women of childbearing age should agree to use contraceptives (such as intrauterine devices, contraceptives or condoms) during the study period and within 6 months after the end of the study; negative serum or urine pregnancy test within 7 days prior to study enrollment And must be non-lactating patients; males should agree to patients who must use contraception during the study period and within 6 months after the end of the study period; 11. Subjects voluntarily joined the study, signed informed consent, and were well-adhered to follow-up.

Exclusion Criteria:

  1. Does not meet the above inclusion criteria;
  2. Those who are allergic or metabolically dying of capecitabine and cisplatin;
  3. The patient has any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, Hyperthyroidism; patients with vitiligo; Asthma has been completely relieved in childhood, and patients who do not need any intervention after adulthood can be included; asthma patients who require bronchodilators for medical intervention cannot be included);
  4. The patient is using immunosuppressive agents or systemic hormonal therapy for immunosuppressive purposes (dose > 10 mg/day of prednisone or other therapeutic hormones) and continues to be used for 2 weeks prior to enrollment;
  5. Radiotherapy contraindications;
  6. Patients with any severe and/or uncontrolled diseases;
  7. Patients with unsatisfactory blood pressure control (systolic blood pressure ≥150mmHg or diastolic blood pressure ≥100 mmHg); myocardial ischemia or myocardial infarction with grade I or above, arrhythmia (including QT interval ≥480ms) and grade I cardiac insufficiency;
  8. Active or uncontrolled serious infections;
  9. Liver diseases such as decompensated liver disease, active hepatitis B (HBV-DNA ≥ 104 copies/ml or 2000 IU/ml) or hepatitis C (positive hepatitis C antibody, and HCV-RNA is higher than the lower limit of detection of the analytical method);
  10. Urine routine indicates that urine protein ≥ ++, and confirmed 24-hour urine protein quantitation > 1.0g;
  11. Imaging shows that the tumor has invaded the important perivascular circumference or that the patient is likely to invade the important blood vessels and cause fatal bleeding during the follow-up study;
  12. Pregnant or lactating women;
  13. Patients with other malignancies within 5 years (except for basal cell carcinoma and cervical carcinoma in situ) that have been cured;
  14. Patients with a history of psychotropic substance abuse who are unable to quit or have a mental disorder;
  15. Patients who have participated in other drug clinical trials within four weeks;
  16. At the discretion of the investigator, there are patients with serious concomitant disease that compromises patient safety or affects the patient's completion of the study;
  17. The investigator believes that it is not suitable for inclusion.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03817658


Contacts
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Contact: Feng Wang 13938244776 fengw010@163.com

Locations
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China, Henan
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, China, 450052
Sponsors and Collaborators
The First Affiliated Hospital of Zhengzhou University
Jiangsu HengRui Medicine Co., Ltd.
Investigators
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Principal Investigator: Feng Wang The First Affiliated Hospital of Zhengzhou University
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Responsible Party: Feng Wang, Doctor, The First Affiliated Hospital of Zhengzhou University
ClinicalTrials.gov Identifier: NCT03817658    
Other Study ID Numbers: SHR-1210--01
First Posted: January 25, 2019    Key Record Dates
Last Update Posted: January 25, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Esophageal Squamous Cell Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases