Phase II Study of Neoadjuvant Anti-PD-1 Antibody SHR-1210 and Radiation in Resectable Esophageal Squamous Cell Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- 3-DCRT or IMRT radiation
- Conditions
- Esophageal Neoplasms
- Sponsor
- Hangzhou Cancer Hospital
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- Pathologic Complete Response Rate
- Last Updated
- 8 years ago
Overview
Brief 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
Investigators
Shixiu Wu
Professor
Hangzhou Cancer Hospital
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically confirmed esophageal squamous cell carcinoma without prior treatments including surgery, chemotherapy, radiotherapy, and targeting treatment.
- •With resectable disease of primary tumor in middle or lower thoracic esophagus and clinical stage Ⅱa-Ⅲ.
- •age:18-75 years, male or female.
- •Can provide either a newly obtained or archival tumor tissue sample.
- •Life expectancy of greater than 12 weeks.
- •Without serious system dysfunction and could tolerate radiotherapy.
- •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.
- •Patients must have normal electrocardiogram results and no history of congestive heart failure.
- •Women of childbearing age should voluntarily take contraceptive measures.
- •Without drug addition
Exclusion Criteria
- •Patients who have or are currently undergoing additional chemotherapy, radiation therapy, targeted therapy or immunotherapy.
- •With unresectable disease including any T4b or M1 disease
- •Complete obstruction of the esophagus, or patients who have the potential to develop perforation
- •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.
- •Known central nervous system (CNS) metastases.
- •Subjects with any active autoimmune disease or history of autoimmune disease.
- •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;
- •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);
- •History of Interstitial Pneumonia or active non-infectious pneumonitis.
- •Known Human Immunodeficiency Virus (HIV) infection、active Hepatitis B or Hepatitis C.
Arms & Interventions
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.
Intervention: 3-DCRT or IMRT radiation
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.
Intervention: anti-PD-1 antibody SHR-1210
Outcomes
Primary Outcomes
Pathologic Complete Response Rate
Time Frame: 2-4 weeks after completion of radiotherapy
the Percentage of Patients Who Have No Evidence of Cancer in Their Surgical Specimen Following Surgery
Secondary Outcomes
- Disease-Free Survival(2 years)
- Numbers of adverse events and the degree of each adverse events according to the NCI CTCAE 4.0 criteria.(6 months)