Efficacy and Safety of Concurrent Sintilimab and Radiotherapy With Immunonutrition Support in Esophageal Cancer: A Phase II Multicenter Clinical Trial
Overview
- Phase
- Phase 2
- Intervention
- Radiotherapy
- Conditions
- Locally Advanced Esophageal Squamous Cell Carcinoma
- Sponsor
- Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- Enrollment
- 57
- Locations
- 9
- Primary Endpoint
- 1-year Progression-free survival rate (PFS)
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
At present, concurrent chemoradiotherapy (cCRT) with platin-based dual-drug regimen is the standard treatment for inoperable, locally advanced esophageal cancer in patients with a good performance status. However, cCRT has substantial toxic effects, and a large number of patients with older age, malnutrition and other morbidities, cannot tolerate cCRT. Several phase II trials showed combining PD-1 inhibitor with definitive cCRT provided encouraging activity and acceptable toxicity in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC).
Therefore, this single-arm, multicenter, phase II trial aims to assess the efficacy and safety of immunotherapy plus radiotherapy with immunonutrition support in patients with LA-ESCC and positive PD-L1 expression who are intolerant to cCRT.
Detailed Description
This single-arm trial is designed to evaluate the efficacy and safety of concurrent immunotherapy (sintilimab) plus radiotherapy with immunonutrition support (enteral nutritional emulsion (TPF-T) followed by consolidation immunotherapy in inoperable patients with locally advanced or early stage esophageal squamous cell carcinoma , who are PD-L1 positive expression and intolerant to cCRT. The eligible patients will receive concurrent treatment consisting of total dose of 50-60 Gy in 25-30 fractions and 200 mg of sintilimab administered every three weeks, along with enteral nutritional emulsion (TPF-T) support (600-1600 ml per day according to the nutrition status evaluation). The primary outcome is 1-year progression-free survival (PFS) rate. The investigators hypothesized PD-L1 inhibitor plus radiotherapy will improve the 1-year PFS from 40% to 60%. Then, 58 patients will be needed in total. The secondary outcomes will include objective response rate (ORR), overall survival (OS), progression-free and overall survival, and incidence of adverse events. This study is approval by the National GCP Center for Anticancer Drugs, Independent Ethics Committee, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College (Study ID: 24/074-4354).
Investigators
JIANYANG WANG
Principal Investigator
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Eligibility Criteria
Inclusion Criteria
- •Aged 18 years or order.
- •Diagnosed with locally advanced or early stage esophageal squamous cell carcinoma by pathological examinations of the primary lesion and imaging examinations, which are not resectable.
- •Confirmed to be unresectable and unable to tolerate synchronous chemoradiotherapy by multidisciplinary consultation, and has not undergone systemic drug therapy in the past.
- •PD-L1 tumor proportion score or combined positive score of ≥1%.
- •At least one measurable lesion on imaging according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.
- •An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 -
- •Expected survival time of more than three months.
- •Adequate organ function defined as the following laboratory indicators:
- •Absolute neutrophil count (ANC) ≥ 1.5×109/L without use of granulocyte colony-stimulating factor in the past 14 days.
- •Platelet count ≥ 100×109/L without blood transfusion in the past 14 days.
Exclusion Criteria
- •Subjects with any of the following conditions cannot participate in the study:
- •A high risk of bleeding or perforation due to clear invasion of adjacent organs (large arteries or trachea) by the tumor, or with fistula.
- •Diagnosed with malignancies other than esophageal cancer within 3 years prior to the first dose (excluding cured basal cell carcinoma or squamous cell carcinoma of the skin and/or radically resected carcinoma in situ).
- •Previous immunological or immunomodulatory drugs as systemic whole-body treatment, including thymic peptides, interferon, interleukins, except for local use to control pleural effusion.
- •Previous chest radiotherapy.
- •A history of allogeneic organ transplantation (except for corneal transplantation) or allogeneic hematopoietic stem cell transplantation.
- •Allergic to the study drug, Sintilimab, or its excipients.
- •A history of human immunodeficiency virus (HIV) infection (i.e., HIV1/2 antibody positive).
- •Untreated active hepatitis B defined as HBsAg positive and HBV-DNA copy number greater than the upper limit of the normal value in the laboratory of the study center.
- •Note: Patients with hepatitis B who meet the following criteria can also be included:
Arms & Interventions
Concurrent immunotherapy and radiotherapy
Sintilimab + radiotherapy + enteral nutritional emulsion (TPF-T)
Intervention: Radiotherapy
Concurrent immunotherapy and radiotherapy
Sintilimab + radiotherapy + enteral nutritional emulsion (TPF-T)
Intervention: Programmed Cell Death Protein 1 Inhibitor
Concurrent immunotherapy and radiotherapy
Sintilimab + radiotherapy + enteral nutritional emulsion (TPF-T)
Intervention: Immunonutrition support
Outcomes
Primary Outcomes
1-year Progression-free survival rate (PFS)
Time Frame: From start of treatment until 1 years of follow-up.
Progression-free survival rate is defined the rate of progress event at 1-years after radiotherapy. Progression event is defined as event of primary tumor and regional recurrence, or distant metastasis
Secondary Outcomes
- Incidence of adverse events(Measured at months 6, 12, 18, and 24.)
- Objective response rate(Measured at 3 months after completion of radiotherapy)
- Progression-free survival(Measured at months 6, 12, 18, and 24.)
- Overall survival rate(Measured at months 6, 12, 18, and 24.)
- Overall survival(From start of treatment until 3 years of follow-up.)