Study of Anti-PD-1/PD-L1 Antibody Plus Apatinib as Second-Line Treatment of Advanced Esophageal Squamous Cell

Esophageal Cancer Clinical Trial

Official title:

A Single-arm, Open-label, Phase Ⅱ Clinical Trial of Anti-PD-1 Antibody SHR-1210 or Anti-PD-L1 Antibody SHR-1316 Combined With Apatinib Mesylate as a Second-line Treatment for Advanced Esophageal Squamous Cell Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03736863
• Other study ID #: FQX-001/MA-EC-II-002/CAP 02
• Status: Recruiting
• Phase: Phase 2
• Start date: December 5, 2019
• Est. completion date: December 30, 2024

Study information

• Verified date: February 2024
• Source: The First Affiliated Hospital of Zhengzhou University
• Contact: Feng Wang
• Phone: 13938244776
• Email: fengw010[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to observe and evaluate the efficacy and safety of Anti-PD-1 antibody SHR-1210 or Anti-PD-L1 antibody SHR-1316 plus apatinib as second-line treatment of advanced esophageal squamous cell.

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. We designed a single-arm, open phase II clinical trial of anti-PD-1 antibody SHR-1210 or Anti-PD-L1 antibody SHR-1316 plus apatinib as second-line treatment of advanced esophageal squamous cell. The purpose of this study is to observe and evaluate the efficacy and safety of Anti-PD-1 antibody SHR-1210 or Anti-PD-L1 antibody SHR-1316 plus apatinib as second-line treatment of advanced esophageal squamous cell.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 125
• Est. completion date: December 30, 2024
• Est. primary completion date: June 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Aged 18-75 years, males or females;

2. Histologically or cytologically confirmed as ESCC, locally advanced and unresectable, with local recurrence (local lymph node metastases) or distant metastases;

3. Having progressed or being intolerant to first-line systemic chemotherapy (including chemotherapy based on cisplatin, taxol or fluorouracil) or chemotherapy combined with immunotherapy. 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;

4. The best overall response of first-line immunotherapy is CR, PR or SD, and PFS = 3 months;

5. 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) ;

6. 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;

7. ECOG: 0~1;

8. Expected survival time = 12 weeks;

9. 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;

10. Doppler ultrasound evaluation: Left ventricular ejection fraction (LVEF) = lower limit of normal (50%).

11. 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;

12. All subjects are recruited on a voluntary basis and sign the informed consent. They are required to be compliant with the study and cooperative with the follow-up.

Exclusion Criteria:

1. 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);

2. 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;

3. ESCC patients with active bleeding in primary lesions;

4. ESCC patients in whom the primary lesions are not surgically resected and are not shrunken in size after radiotherapy;

5. Patients who have received treatment with VEGFR inhibitors, such as sorafenib, sunitinib, and apatinib;

6. Any of the following conditions that will interfere with oral medications: unable to swallow, having received gastroenterostomy, chronic diarrhea and intestinal obstruction;

7. Brain metastasis or brain metastases that have disappeared in less than 3 months;

8. 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;

9. Patients whose wounds or bone fractures remain unhealed for a long period of time;

10. 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;

11. Patients who have experienced arterial/venous thrombotic events within six months, such as cerebrovascular accidents (including transient ischemic attack), deep venous thrombosis and pulmonary embolism;

12. The invasion of important blood vessels by the tumour or a high probability of the invasion of important blood vessels by the tumor that may lead to lethal hemorrhage in the study period ahead, as judged by the investigator according to the radiological examination;

13. Pregnancy or lactation;

14. Patients who have a history of other malignancies in the past five years (except for the cured basal cell carcinoma and cervical carcinoma in situ);

15. Patients who have a history of psychotropic drug abuse and unable to quit or having mental disorders;

16. Patients who have participated in other clinical trials of drugs in the past four weeks;

17. Patients who have concomitant diseases that may severely impair the safety of patients or make the patients unable to complete the study, as judged by the investigator;

18. Other patients who are considered inappropriate for participation by the investigator.

Related Conditions & MeSH terms

• Esophageal Cancer

Intervention

Drug:
• Apatinib+ SHR-1210(Camrelizumab)
Apatinib 250mg, q.d.po+SHR-1210(Camrelizumab)200 mg,Intravenous injection,q2W
• Apatinib+ SHR-1316(Adebrelimab)
Apatinib 250mg, q.d.po+SHR-1316(Adebrelimab) 1200 mg,Intravenous injection,q2W

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Zhengzhou University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	the proportion of patients with a confirmed complete response or partial response on two consecutive occasions=4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	up to 1 year
Secondary	Disease Control Rate (DCR)	the proportion of patients with a best overall response of confirmed complete or partial response, or stable disease (CR; + PR + SD)	up to 1 year
Secondary	Progression-free Survival (PFS)	the time from treatment initiation to the first disease progression or death from any cause	up to 2 year
Secondary	Duration of response(DOR)	the time from the first confirmed response date to the first disease progression or death date	up to 2 year
Secondary	Time to response(TTP)	the time from treatment to first confirmed tumour response	up to 1 year
Secondary	Overall survival(OS)	the time from treatment initiation until death from any reason	up to 2 year
Secondary	3- and 6-month PFS rates	Progression-free survival rates at 3- and 6-month	up to 6 months
Secondary	6-, 9- and 12-month OS rates	overall survival rates at 6-, 9- and 12-month	up to 12 months
Secondary	adverse events(Safety)	adverse events	up to 2 years