Anti-PD-1 Antibody SHR-1210 Combined With Apatinib Versus SHR-1210 in the Second-line Treatment of Advanced Esophageal Squamous Cell Carcinoma：A Multicentre，Randomized， Open Label，Phase 3 Study

Feng Wang0 sites234 target enrollmentDecember 5, 2021

ConditionsEsophageal Cancer

InterventionsCamrelizumab Apatinib

DrugsCamrelizumab Apatinib

Overview

Phase: Phase 3
Intervention: Camrelizumab
Conditions: Esophageal Cancer
Sponsor: Feng Wang
Enrollment: 234
Primary Endpoint: Overall survival(OS)
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

The purpose of this study is to observe and evaluate the efficacy and safety of Anti-PD-1 antibody SHR-1210 plus apatinib versus SHR-1210 as second-line treatment of advanced esophageal squamous cell.

Detailed Description

The incidence of esophageal cancer is ranked seventh in the world, and the mortality rate ranks sixth in the world. At present, the first-line treatment of advanced esophageal cancer is mainly based on the combination of paclitaxel, cisplatin and fluorouracil. After the failure of first-line treatment, there is no standard second-line treatment. Recently the study of KEYNOTE181, ATTRACTION-3 and ESCORT had confirmed that PD-1 single drug in the second-line treatment of esophageal cancer is better than the previous traditional chemotherapy, and has become a new standard treatment. In order to further improve the therapeutic efficacy and prognosis of advanced esophageal squamous cell carcinoma, we designed this phase III clinical study to compare the efficacy and safety of shr-1210 combined with apatinib and shr-1210 in the second-line treatment of esophageal squamous cell carcinoma.

Registry

clinicaltrials.gov

Start Date

December 5, 2021

End Date

June 30, 2023

Last Updated

4 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Feng Wang

Responsible Party

Sponsor Investigator

Principal Investigator

Feng Wang

doctor

The First Affiliated Hospital of Zhengzhou University

Eligibility Criteria

Inclusion Criteria

•Aged 18-75 years, males or females;
•Histologically or cytologically confirmed as ESCC, locally advanced and unresectable, with local recurrence (local lymph node metastases) or distant metastases;
•Having progressed or being intolerant to first-line systemic chemotherapy (including chemotherapy based on cisplatin, taxol or fluorouracil). Patients are also eligible if they progress after maintenance treatment following the first-line chemotherapy, or if patients with postoperative recurrence or metastasis progress after concurrent radiochemotherapy. As for the radical concurrent chemoradiotherapy, neoadjuvant/adjuvant treatment (chemotherapy or radiochemotherapy), if patients progress during the treatment or within six months after treatment, it is considered as a failure of first-line treatment;
•According to the Response Evaluation Criteria In Solid Tumour (RECIST 1.1), there is at least one measurable lesion, which has not received any local treatment, such as radiotherapy (if the lesion within the region of the previous radiotherapy is confirmed to progress and satisfies RECIST1.1, it can be also selected as the target lesion) ;
•Tissue samples should be provided for biomarker analysis. The newly harvested tissues are preferred. If the newly harvested tissues are not available, 5-8 archival paraffin sections (5 um thick) can be provided;
•ECOG: 0\~1;
•Expected survival time ≥ 12 weeks;
•Adequate function of major organs defined as:(1) Routine blood test: a. HB ≥ 90 g/L; b. ANC ≥ 1.5 × 109/L; c. PLT ≥ 80 × 109/L;(2) Biochemical test: a. ALB ≥ 30 g/L; b. ALT and AST ≤ 2.5 ULN; if there is no liver metastasis, ALT and AST ≤ 5 ULN; c. TBIL ≤ 1.5ULN; d. Plasma Cr ≤ 1.5 ULN or creatinine clearance rate (CCr) ≥ 60 mL/min;
•Doppler ultrasound evaluation: Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%).
•Women of childbearing age should consent to take contraception measures during the study period and within 6 months after the end of the study (eg., intrauterine device, oral contraceptive pills or condoms). The subjects must be negative for the serum or urine pregnancy test within 7 days before the recruitment. The female subjects must be non-lactating women. Males should consent to take contraception measures during the study period and within 6 months after the end of the study;

Exclusion Criteria

•Patients who have any active autoimmune diseases or a past history of autoimmune diseases (including but not limited to the following: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, and hyperthyroidism; leukoderma. Subjects with fully remitted childhood asthma and no need for any intervention during adulthood can be included; those still having the need for bronchodilators for medical intervention cannot be included);
•Patients who are currently on immunosuppressors or systemic hormone therapy for immunosuppressive purposes (dose \> 10 mg/day, prednisone or other hormones with equivalent efficacy), and continue taking them within 2 weeks before recruitment;
•ESCC patients with active bleeding in primary lesions;
•ESCC patients in whom the primary lesions are not surgically resected and are not shrunken in size after radiotherapy;
•Patients who have received treatment with VEGFR inhibitors, such as sorafenib, sunitinib, and apatinib;
•Any of the following conditions that will interfere with oral medications: unable to swallow, having received gastroenterectomy, chronic diarrhea and intestinal obstruction;
•Brain metastasis or brain metastases that have disappeared in less than 3 months;
•Patients who have any severe and/or uncontrolled diseases, including: poor blood pressure control (systolic pressure ≥ 150 mmHg or diastolic pressure ≥ 100 mmHg); having myocardial ischemia or myocardial infarction and arrhythmia of Grade 1 and above (including QT interval ≥ 480 ms) and cardiac insufficiency of Grade 1; active or uncontrollable severe infection; liver diseases, such as decompensated liver failure, active hepatitis B (HBV-DNA ≥ 104 copy number/mL or 2000 IU/mL) or hepatitis C (positive for anti-HCV antibodies, and HCV-RNA higher than the lower limit of detection with the analytical method); routine urine test indicates urine protein ≥++ and confirms that the 24-hour urinary protein quantification\>1.0 g;
•Patients whose wounds or bone fractures remain unhealed for a long period of time;
•Pneumorrhagia \> NCI-CTC AE Grade1 within four weeks before recruitment; bleeding at other positions \>NCI-CTC AE Grade 2 within four weeks before recruitment; having a bleeding tendency (eg., active peptic ulcer) or currently receiving thrombolytic or anticoagulant therapy, such as warfarin, heparin, or their analogs;