Study of PD-1 Antibody Combined With Chemoradiotherapy in Oligometastatic Esophageal Cancer

A Phase II Study of PD-1 Antibody Combined With Chemoradiotherapy in Oligometastatic Esophageal Squamous Cell Carcinoma

Chemoradiotherapy（CRT） is the main treatment for esophageal cancer patients with recurrent desease，and checkpoint blockade (PD-1) have been shown to be effective in advanced esophageal cancer. Therefore, PD-1 combined with chemoradiotherapy （CRT）may further improve the efficacy and become a new method for the treatment of esophageal cancer.This study intends to conduct a single-arm, prospective clinical study, aiming to evaluate the safety and efficacy of PD-1 combined with chemoradiotherapy(CRT) in patients with oligometastatic esophageal squamous cell carcinoma.

Study Overview

• Status: Recruiting
• Conditions: Oligometastatic Disease; Immunotherapy; Esophagus Cancer; Chemoradiotherapy
• Intervention / Treatment: Drug: PD-1 antibody; Radiation: Chemoradiation; Drug: Albumin-Bound Paclitaxel; Drug: Cisplatin

• Study Type: Interventional
• Enrollment (Anticipated): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
      • Contact: Xin Wang, MD; Email: beryl_wx2000@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

•≥18 years；

• Esophageal squamous cell carcinomas；
• After radical treatment including surgery or definitive chemoradiotherapy
• Definition of oligometastases：≤3 metastases, including tumor beds and recurrent anastomotic sites；regional lymph node is defined as one metastatic site（AJCC8th, supraclavicular, mediastinal, abdominal）；metastases lesion in liver, lung, bone and brain is no more than 1.
• Karnofsky performance status(KPS)≥ 70；
• No immunotherapy were performed after recurrence；
• a white-cell count of at least 3500G/L, a hemoglobin concentration of at least 100 g/L, a platelet count of at least 100,000/lL, aspartate aminotransferase and alanine aminotransferase levels of within 1.5 times the upper limit of normal, a serum bilirubin level of 1.5 mg/dL or less, a creatinine level of 1.1 mg/dL or less;
• Hepatitis virus indicators: normal or hepatitis virus DNA titer less than 500 at the same time in an infectious disease hospital, and with the consent of the doctor can be treated；

Exclusion Criteria:

• Pregnancy, possible pregnancy, or breast-feeding;
• Psychological, family, social and other factors lead to uninformed consent;
• An esophageal mediastinal fistula and/or an esophageal tracheal fistula prior to treatment;
• Serious complications such as ischemic heart disease, arrhythmias, or other types of heart disease requiring treatment; liver cirrhosis; interstitial pneumonia or pulmonary fibrosis; active gastrointestinal bleeding; mental disorders being treated with antipsychoticagents or requiring treatment;
• Controlled diabetes mellitus;
• A history of autoimmune disease, autoimmune disease (such as colitis, hepatitis, hyperthyroidism, including but not limited to these disease or syndrome) and a history of immune deficiency, including test positive for HIV, or has other acquired, congenital immunodeficiency disease, or have a history of organ transplantation and the history of allogeneic bone marrow transplantation;
• A history of interstitial lung disease and a history of non-infectious pneumonia;
• Active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 Copies /mL), hepatitis C ;(positive HCV antibody and HCV-RNA above the detection threshold of the assay）
• Any situation that is unstable or may compromise patient safety and compliance ;
• Active infections, such as active tuberculosis, are present;

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: Chemoradiotherapy Combined With PD-1 Antibody; The arm received chemoradiotherapy, 50-60Gy (BED) was given (1.8-2 Gy or 3-4Gy once daily , 5 days a week) to recurrent sites combined with chemotherapy（Cisplatin 75 mg/m2/day 1, and albumin paclitaxel 150 mg/m2/day 1 , every 3 weeks, 2 cycles ).PD-1 antibody (Tislelizumab) was performed simultaneously with concurrent chemoradiotherapy (Triprizumab 200mg，d1，every 3 weeks，2 cycles). After completion of chemoradiotherapy, PD-1 antibody was given continuously with 2-4 cycles of chemotherapy (the same regimen with concurrent chemotherapy) until 1 year or desease progression.

Drug: PD-1 antibody; 200mg, d1, q3W; Radiation: Chemoradiation; 50-60Gy (BED) was given (1.8-2 Gy or 3-4Gy once daily , 5 days a week; Drug: Albumin-Bound Paclitaxel; 150mg/m2, d1, q3W; Drug: Cisplatin; 75mg/m2, d1, q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Locoregional control rate	3 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiomics analysis	Analysis of correlation between radiomics signature extracted by LASSO and the rate of participants who achieve pathological complete response (pCR) and the overall survival based on MRI and CT simulation.	1 year, 2 year, 3 year, 5 year
Number of participants with acute toxicities	Acute toxicities are evaluated by NCI-CTC version 5.0	10 week, from the start of treatment to 1 month after chemoradiotherapy
Tumor response rate		2-3 months
Progression free survival		1 year, 2 year, 3 year
Overall survival		1 year, 2 year, 3 year
Objective response rate	Objective Response Rate are evaluated by RECIST 1.1	5.5 week

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Anticipated): September 30, 2023
• Study Completion (Anticipated): September 30, 2023

Study Registration Dates

• First Submitted: March 15, 2021
• First Submitted That Met QC Criteria: March 26, 2021
• First Posted (Actual): March 30, 2021

Study Record Updates

• Last Update Posted (Actual): March 30, 2021
• Last Update Submitted That Met QC Criteria: March 26, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Antibodies; Albumin-Bound Paclitaxel
• Other Study ID Numbers: NCC2749

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