Trial Title:
Efficacy and Safety of Concurrent PD-1 Inhibitor and Radiotherapy With Immunonutrition for Esophageal Squamous Cell Carcinoma
NCT ID:
NCT06342167
Condition:
Locally Advanced Esophageal Squamous Cell Carcinoma
Sintilimab
Radiotherapy
Concurrent Chemoradiotherapy
Immunonutrition
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Esophageal Squamous Cell Carcinoma
Immune Checkpoint Inhibitors
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
Radiotherapy
Description:
Interventions consist of 50-60 Gy in 25-30 fractions of radiotherapy.
Arm group label:
Concurrent immunotherapy and radiotherapy
Intervention type:
Drug
Intervention name:
Programmed Cell Death Protein 1 Inhibitor
Description:
200 mg of Sintilimab administered every three weeks concurrently with radiotherapy and
after radiotherapy as consolidation therapy up to 1year.
Arm group label:
Concurrent immunotherapy and radiotherapy
Other name:
PD-1 Inhibitor
Intervention type:
Dietary Supplement
Intervention name:
Immunonutrition support
Description:
600-1600 ml of TPF-T per day according to the nutrition status evaluation
Arm group label:
Concurrent immunotherapy and radiotherapy
Other name:
enteral nutritional emulsion
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).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Aged 18 years or order.
2. 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.
3. Confirmed to be unresectable and unable to tolerate synchronous chemoradiotherapy by
multidisciplinary consultation, and has not undergone systemic drug therapy in the
past.
4. PD-L1 tumor proportion score or combined positive score of ≥1%.
5. At least one measurable lesion on imaging according to the Response Evaluation
Criteria in Solid Tumors (RECIST) version 1.1.
6. An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 -2.
7. Expected survival time of more than three months.
8. Adequate organ function defined as the following laboratory indicators:
1. Absolute neutrophil count (ANC) ≥ 1.5×109/L without use of granulocyte
colony-stimulating factor in the past 14 days.
2. Platelet count ≥ 100×109/L without blood transfusion in the past 14 days.
3. Hemoglobin > 9g/dL without blood transfusion or use of
erythropoietin-stimulating agents in the past 14 days.
4. Total bilirubin ≤ 1.5×upper limit of normal (ULN).
5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5×ULN.
6. Creatinine ≤ 1.5×ULN and creatinine clearance calculated using the
Cockcroft-Gault formula) ≥ 60 ml/min.
7. Good coagulation function, defined as an international normalized ratio (INR)
or prothrombin time (PT) ≤ 1.5×ULN.
8. Normal thyroid function, defined as thyroid-stimulating hormone (TSH) within
the normal range. If the baseline TSH is outside the normal range, subjects
with total T3 (or FT3) and FT4 within the normal range can still be included.
9. Normal cardiac enzyme spectrum (or clinically insignificant laboratory
abnormalities as determined by the investigator)
9. Negative pregnancy test (urine or serum) within 3 days before the first dose of
study drug for female subjects of childbearing potential. If the urine pregnancy
test cannot be confirmed as negative, a blood pregnancy test is required.
Non-childbearing potential female is defined as postmenopausal for at least 1 year
or has undergone surgical sterilization or hysterectomy.
10. Willing to sign the informed consent form.
Exclusion Criteria:
Subjects with any of the following conditions cannot participate in the study:
1. A high risk of bleeding or perforation due to clear invasion of adjacent organs
(large arteries or trachea) by the tumor, or with fistula.
2. 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).
3. Previous immunological or immunomodulatory drugs as systemic whole-body treatment,
including thymic peptides, interferon, interleukins, except for local use to control
pleural effusion.
4. Previous chest radiotherapy.
5. A history of allogeneic organ transplantation (except for corneal transplantation)
or allogeneic hematopoietic stem cell transplantation.
6. Allergic to the study drug, Sintilimab, or its excipients.
7. A history of human immunodeficiency virus (HIV) infection (i.e., HIV1/2 antibody
positive).
8. 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:
1. HBV viral load <1000 copies/ml (200IU/ml) before the first dose; the patient
should receive anti-HBV treatment throughout chemotherapy in the entire study
to avoid viral reactivation.
2. For patients who are anti-HBc (+), HBsAg (-), anti-HBs (-), and HBV viral load
(-), no prophylactic anti-HBV treatment is required, but close monitoring of
viral reactivation is needed.
9. Active hepatitis C virus (HCV) infection defined as HCV antibody positive and
HCV-RNA levels higher than the detection limit.
10. Having received live vaccines within 30 days prior to the first dose (Cycle 1, Day
1).
Note: It is allowed to receive inactivated virus vaccines for seasonal influenza
within 30 days prior to the first dose, but attenuated live influenza vaccines
administered intranasally are not allowed.
11. Pregnant or lactating women;
12. Any serious or uncontrollable systemic diseases, such as:
1. Significant and symptomatic abnormalities in rhythm, conduction or morphology
on resting electrocardiogram, such as complete left bundle branch block,
second-degree or higher heart block, ventricular arrhythmia, or atrial
fibrillation;
2. Unstable angina, congestive heart failure, or chronic heart failure classified
as New York Heart Association (NYHA) class ≥ 2;
3. Any arterial thrombosis, embolism or ischemic events, such as myocardial
infarction, unstable angina, cerebrovascular accident or transient ischemic
attack, occurring within 6 months prior to enrollment;
4. Poor blood pressure control defined as systolic blood pressure > 140 mmHg
and/or diastolic blood pressure > 90 mmHg;
5. A history of non-infectious pneumonia requiring glucocorticoid therapy within 1
year prior to initial treatment, or current clinical activity of interstitial
lung disease;
6. Active pulmonary tuberculosis;
7. Active or uncontrolled infections requiring systemic therapy;
8. Active diverticulitis, abdominal abscess, or gastrointestinal obstruction;
9. Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic
active hepatitis;
10. Poorly controlled diabetes (fasting blood glucose (FBG) > 10mmol/L);
11. Urine protein ≥ ++ on routine urinalysis, with confirmed 24-hour urine protein
quantification > 1.0 g;
12. Psychiatric disorders that are unable to comply with treatment.
13. Any other medical histories, disease evidence, treatment, or laboratory values that
may interfere with the test results, hinder the full participation in the study, or
other situations that the investigator deems unsuitable for inclusion due to
potential risks.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Address:
City:
Beijing
Zip:
100021
Country:
China
Facility:
Name:
Department of Radiation Oncology，Clinical Oncology School of Fujian Medical University，Fujian Cancer Hospital
Address:
City:
Fujian
Country:
China
Facility:
Name:
Department of Oncology, Affiliated Hospital, Hebei University of Engineering
Address:
City:
Handan
Country:
China
Facility:
Name:
Department 1st of Radiation Oncology, Anyang Tumor Hospital
Address:
City:
Anyang
Country:
China
Facility:
Name:
Department of Radiation Oncology the first affiliated hospital of Xinxiang Medical University
Address:
City:
Xinxiang
Country:
China
Facility:
Name:
Department of Radiation Oncology, General Hospital of Ningxia Medical University
Address:
City:
Yinchuan
Country:
China
Facility:
Name:
Department of Radiation Oncology，Fei County People's Hospital
Address:
City:
Feixian
Country:
China
Facility:
Name:
Department of Radiation Oncology, Affiliated hospital of Jining Medical University
Address:
City:
Jining
Country:
China
Facility:
Name:
Taizhou hospital of Wenzhou Medical University
Address:
City:
Taizhou
Zip:
317000
Country:
China
Start date:
March 14, 2024
Completion date:
December 1, 2026
Lead sponsor:
Agency:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Agency class:
Other
Source:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06342167
