Combination of Radiation Therapy and Anti-PD-1 Antibody SHR-1210 in Treating Patients With Esophageal Cancer

Phase II Study of Radiation Therapy With Anti-PD-1 Antibody SHR-1210 in Treating Patients With Unresectable Esophageal Cancer

The objective of this study is to evaluate the efficacy and safety of radiation therapy combined with anti-PD-1 antibody SHR-1210 in patients with esophageal cancer

Study Overview

• Status: Completed
• Conditions: Esophageal Neoplasms; Esophageal Diseases; Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Radiation; Drug: SHR-1210

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310002
      • Hangzhou Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. age:18-75 years, male or femal.
2. Histologically or cytologically confirmed Squamous Cell Carcinoma of the Esophagus, locally advanced, unresectable disease.
3. Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
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. Adequate organ function.
8. Female: child bearing potential, a negative urine or serum pregnancy test result within 72 h before study treatment. Participants of reproductive potential must be willing to use adequate contraception for the course of the study through 3 months after the last dose of SHR-1210.
9. Patient has given written informed consent.

Exclusion Criteria:

1. Patients who have or are currently undergoing additional chemotherapy, radiation therapy, targeted therapy or immunotherapy.
2. Complete obstruction of the esophagus, or patients who have the potential to develop perforation
3. 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.
4. Known central nervous system (CNS) metastases.
5. Subjects with any active autoimmune disease or history of autoimmune disease.
6. 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;
7. 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);
8. History of Interstitial Pneumonia or active non-infectious pneumonitis.
9. Known Human Immunodeficiency Virus (HIV) infection、active Hepatitis B or Hepatitis C.
10. Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) agent.
11. Known history of hypersensitivity to macromolecular protein preparation or any components of the SHR-1210 formulation.
12. 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 treament. Except: inhalation or topical corticosteroids. Doses > 10 mg/day prednisone or equivalen for replacement therapy.
13. Has received prior anti-cancer monoclonal antibody (mAb), chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to study Day 1 or not recovered from adverse events due to a previously administered agent.
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Experimental Group; Radiation to 60 Gy, 5 x per week, for 6 weeks. Radiation begun the day after the first dose of SHR-1210. SHR-1210 (200mg fixed dose every 2 weeks for 5 cycles) will be administered as an intravenous infusion over 60 minutes.	Drug: Radiation; RT to 60 Gy, 5 x per week，for 6 weeks. Radiation begun the day after the first dose of SHR-1210; Drug: SHR-1210; SHR-1210 (200mg fixed dose every 2 weeks for 5 cycles) will be administered as an intravenous infusion over 60 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	ORR was evaluated 4-8 weeks after completion of RT and was recorded according to RECIST, version 1.1.	4-8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-emergent adverse events	Incidence of treatment-emergent adverse events would be assessed based on the common toxicity criteria for adverse events version 4.0 (CTCAE v4.0) and EORTC criterion.	year 0 - year 1
Local-regional free survival (LRFS)	LRFS was calculated from the date of treatment initiation to the date of documented failure.	year 0 - year 3
Overall survival	OS was determined as the time (in months) between the first day of therapy and the last follow-up or the date of death.	year 0 - year 3
Health-related quality of life (HRQoL)	HRQoL measured by standardized EORTC questionaires (EORTC QLQ-C30)	From baseline to one year after RT.
Health-related quality of life (HRQoL)	HRQoL measured by standardized EORTC questionaires (EORTC QLQ-OES18)	From baseline to one year after RT.

Collaborators and Investigators

• Sponsor: Hangzhou Cancer Hospital
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 14, 2017
• Primary Completion (ACTUAL): June 30, 2019
• Study Completion (ACTUAL): June 30, 2019

Study Registration Dates

• First Submitted: June 13, 2017
• First Submitted That Met QC Criteria: June 13, 2017
• First Posted (ACTUAL): June 14, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 17, 2020
• Last Update Submitted That Met QC Criteria: August 13, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Esophageal Squamous Cell Carcinoma; Radiation; Anti-PD-1 Antibody
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophageal Diseases
• Other Study ID Numbers: HangzhouCH08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No