Neoadjuvant Anti-PD-1 Antibody SHR-1210 and Radiation in Resectable Esophageal Squamous Cell Carcinoma

Esophageal Neoplasms Clinical Trial

Official title:

Phase II Study of Neoadjuvant Anti-PD-1 Antibody SHR-1210 and Radiation in Resectable Esophageal Squamous Cell Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03200691
• Other study ID #: HangzhouCH09
• Status: Recruiting
• Phase: Phase 2
• First received: June 22, 2017
• Last updated: August 3, 2017
• Start date: August 10, 2017
• Est. completion date: July 1, 2020

Study information

• Verified date: August 2017
• Source: Hangzhou Cancer Hospital
• Contact: shixiu wu, MD
• Phone: +8657186826086
• Email: wushixiu[@]medmail.com.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to evaluate the efficacy and safety of radiation therapy combined with anti-PD-1 antibody SHR-1210 followed by surgery in treating patients with resectable esophageal squamous cell carcinoma

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 21
• Est. completion date: July 1, 2020
• Est. primary completion date: June 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Patients must have histologically confirmed esophageal squamous cell carcinoma without prior treatments including surgery, chemotherapy, radiotherapy, and targeting treatment.

2. With resectable disease of primary tumor in middle or lower thoracic esophagus and clinical stage ?a-?.

3. age:18-75 years, male or female.

4. Can provide either a newly obtained or archival tumor tissue sample.

5. ECOG 0-1.

6. Life expectancy of greater than 12 weeks.

7. Without serious system dysfunction and could tolerate radiotherapy.

8. Patients must have normal marrow function with a hemoglobin (HGB) of =90g/L, an white blood cell (WBC) counts of =4.0×109/L,a neutrophil count of =2.0×109/L, , a platelet count of =100×109/L, a total bilirubin (TBil) of =1.5 upper normal limitation (UNL), a creatinine (Cr) of = 1.5 UNL, alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) of =2.5 UNL.

9. Patients must have normal electrocardiogram results and no history of congestive heart failure.

10. Women of childbearing age should voluntarily take contraceptive measures.

11. Without drug addition

12. Patients must be with good compliance and agree to accept follow-up of disease progression and adverse events

13. Patients must give written informed consent signed voluntarily by patients themselves or their supervisors witted by doctors.

Exclusion Criteria:

1. Patients who have or are currently undergoing additional chemotherapy, radiation therapy, targeted therapy or immunotherapy.

2. With unresectable disease including any T4b or M1 disease

3. Complete obstruction of the esophagus, or patients who have the potential to develop perforation

4. Other malignancy within 5 years prior to entry into the study, expect for curatively treated basal cell and squamous cell carcinoma of the skin and/or curatively resected in-situ cervical and/or breast cancers.

5. Known central nervous system (CNS) metastases.

6. Subjects with any active autoimmune disease or history of autoimmune disease.

7. Uncontrolled clinically significant heart disease, including but not limited to the following: (1) > NYHA II congestive heart failure; (2) unstable angina, (3) myocardial infarction within the past 1 year; (4) clinically significant supraventricular arrhythmia or ventricular arrhythmia requirement for treatment or intervention;

8. Active infection or an unexplained fever > 38.5°C during screening or before the first scheduled day of dosing (subjects with tumor fever may be enrolled at the discretion of the investigator);

9. History of Interstitial Pneumonia or active non-infectious pneumonitis.

10. Known Human Immunodeficiency Virus (HIV) infection?active Hepatitis B or Hepatitis C.

11. Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) agent.

12. Known history of hypersensitivity to macromolecular protein preparation or any components of the SHR-1210 formulation.

13. Concurrent medical condition requiring the use of cortisol (>10mg/day Prednisone or equivalent dose) or other systematic immunosuppressive medications within 14 days before the study treatment. Except: inhalation or topical corticosteroids. Doses > 10 mg/day prednisone orequivalent for replacement therapy.

14. Received a live vaccine within 4 weeks of the first dose of study medication.

15. Pregnancy or breast feeding.

16. Decision of unsuitableness by principal investigator or physician-in-charge.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Diseases
• Esophageal Neoplasms

Intervention

Radiation:
• 3-DCRT or IMRT radiation
Radiation of primary tumor and local lymph nodes with 95% planning target volume (PTV) of 40 Gy/20f.

Drug:
• anti-PD-1 antibody SHR-1210
SHR-1210 (200mg fixed dose every 2 weeks for 2 cycles) will be administered as an intravenous infusion over 60 minutes.

Locations

Country	Name	City	State
China	Hangzhou Cancer Hospital	Hangzhou	Zhejiang

Sponsors (2)

Lead Sponsor	Collaborator
Hangzhou Cancer Hospital	Jiangsu HengRui Medicine Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic Complete Response Rate	the Percentage of Patients Who Have No Evidence of Cancer in Their Surgical Specimen Following Surgery	2-4 weeks after completion of radiotherapy
Secondary	Disease-Free Survival	Defined as the interval between the start date of treatment and the date of occurrence of progressive disease or death from any cause.	2 years
Secondary	Numbers of adverse events and the degree of each adverse events according to the NCI CTCAE 4.0 criteria.	From the date of randomization to 6 months after esophagectomy. An expected average of 6 months	6 months