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

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

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

Study Overview

• Status: Unknown
• Conditions: Esophageal Neoplasms; Esophageal Diseases
• Intervention / Treatment: Radiation: 3-DCRT or IMRT radiation; Drug: anti-PD-1 antibody SHR-1210

• Study Type: Interventional
• Enrollment (Anticipated): 21
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shixiu Wu, MD; Phone Number: +8657186826086; Email: wushixiu@medmail.com.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310002
      • Recruiting
      • Hangzhou Cancer Hospital
      • Contact: Shixiu Wu, MD; Phone Number: +8657186826086; Email: wushixiu@medmail.com.cn

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. 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 Ⅱa-Ⅲ.
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Nimotuzumab with radiotherapy; Patients will receive neoadjuvant radiotherapy with concurrent anti-PD-1 antibody SHR-1210. Radiation of primary tumor and local lymph nodes with 95% planning target volume (PTV) of 40Gy/20f. SHR-1210 200mg fixed dose every 2 weeks delivered concurrent with radiation therapy. After 2-4 weeks of neoadjuvant treatment, patients will be evaluated by a multidisciplinary teams (MDTs) and esophagectomy will be given for patients with resectable disease.

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Anticipated): August 10, 2017
• Primary Completion (Anticipated): June 30, 2018
• Study Completion (Anticipated): July 1, 2020

Study Registration Dates

• First Submitted: June 22, 2017
• First Submitted That Met QC Criteria: June 26, 2017
• First Posted (Actual): June 27, 2017

Study Record Updates

• Last Update Posted (Actual): August 7, 2017
• Last Update Submitted That Met QC Criteria: August 3, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: PD-1; Esophageal Squamous Cell Carcinoma; Neoadjuvant treatment
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophageal Diseases; Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: HangzhouCH09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No