Neoadjuvant Immunotherapy and Chemoradiotherapy for Locally Advanced Esophagogastric Junction Adenocarcinoma (NICLA)
Primary Purpose
Adenocarcinoma of Esophagogastric Junction
Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
neoadjuvant Radiation plus SOX and PD-1 antibody
Sponsored by

About this trial
This is an interventional treatment trial for Adenocarcinoma of Esophagogastric Junction focused on measuring PD-1, neoadjuvant therapy, radiotherapy
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed adenocarcinoma of esophagogastric junction, and Her-2 negative.
- Clinically diagnosed stage T3+orN+M0, according to CT/MRI scan.
- No prior anti-tumor treatment, including surgery, chemotherapy, radiotherapy, and targeted therapy.
- Eastern Cooperative Oncology Group(ECOG) performance status(PS) 0-1.
- At least one evaluable lesion in abdominal CT/MRI according to RESIST 1.1 is required.
- Expected survival ≥6 months.
- Adequate organ function, Hemoglobin ≥90g/L; White blood cells ≥3.0×109/L; neutrophil count ≥1.5×109/L; Platelets ≥100×109/L; Serum creatinine (SCr) ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance rate ≥ 50ml/min (Cockcroft-Gault formula); Total bilirubin (TBIL) ≤ 1.5 times the ULN; Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≤ 2.5 times the ULN; Urine protein < 2+; if urine protein ≥ 2+, 24-hour urine protein quantification shows that protein must be ≤ 1 g.
- Normal coagulation function, no active bleeding and thrombotic diseases: International Standardized Ratio INR≤1.5×ULN; Partial thromboplastin time APTT≤1.5×ULN; Prothrombin time PT≤1.5ULN;
- Previous use of anti-tumor Chinese medicines, proprietary Chinese medicines, and immunomodulators (such as thymosin, interleukin, etc.) must be ≥ 2 weeks from the start of the study medication;
- Female patients should not be pregnant or breast feeding. Male should contraception.
- Able and willing to give informed consent to participate.
- Those who are expected to have good compliance.
Exclusion Criteria:
- Existence of other active malignant tumors within 5 years or at the same time.
- Already received chemotherapy, radiation therapy, targeted or immunotherapy.
- Have any active autoimmune disease or history of autoimmune disease.
- Patients with congenital or acquired immunodeficiency.
- Use of immunosuppressive drugs within 14 days before the study start.
- Administer live attenuated vaccines within 4 weeks before the study start.
- Suffering from uncontrolled cardiac clinical symptoms or diseases, such as (1) NYHA II and above heart failure (2) unstable angina pectoris (3) myocardial infarction within 1 year (4) poorly controlled arrhythmia.
- Patients with past and current interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, etc., and severely impaired lung function.
- Suffering from active pulmonary tuberculosis.
- Complicated severe infection within 4 weeks before the the study start, or unexplained fever >38.5°C during the screening period/before the study start.
- Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
13. Allergic to any drug in this study. 14. Combined with other severe, acute and chronic diseases that may increase the risk of participating.
15.Participators who had been recruited by other clinical trial within three months.
Sites / Locations
- Peking University People's Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Neoadjuvant therpy
Arm Description
Neoadjuvant chemoradiation plus SOX and PD-1 antibody
Outcomes
Primary Outcome Measures
Pathological Complete Responce (pCR) Rate
Proportion of patients with AEG who received neoadjuvant theray with radiation plus PD-1 antibody and SOX regimen and postoperative pathological examination shows pathological complete responce
Secondary Outcome Measures
R0 Resection Rate
Proportion of patients with AEG who received surgery with pathological pathological examination proved microscopically margin-negative resection
Progression Free Survival (PFS)
Disease Free Survival was defined as the time from the date of surgery to the date of the local recurrence, and/or distant disease, or tumor-related death.
Adverse Events
For any adverse reactions, the researchers refer to the National Cancer Institute (NCI) standard of common toxicity (CTC)
Surgery Morbidity
Surgical morbidity reported according to Clavien-Dindo classification
Full Information
NCT ID
NCT05505461
First Posted
August 15, 2022
Last Updated
August 15, 2022
Sponsor
Peking University People's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05505461
Brief Title
Neoadjuvant Immunotherapy and Chemoradiotherapy for Locally Advanced Esophagogastric Junction Adenocarcinoma
Acronym
NICLA
Official Title
Efficacy and Safety of PD-1 Combined With Long-term Concurrent Neoadjuvant Chemoradiotherapy and Chemotherapy in the Treatment of Resectable Locally Advanced Esophagogastric Junction Adenocarcinoma: A Phase II Study
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 2023 (Anticipated)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
December 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking University People's Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study was to evaluate the effect and safety of concurrent PD-1 antibody-based long-term radiotherapy followed by 2 cycles SOX with PD-1 in patients with locally advanced adenocarcinoma of esophagogastric junction.
Detailed Description
The incidence of adenocarcinoma of the esophagogastric junction (AEG) is increasing in Asian countries and Western Contries. Surgical resection is the most important treatment for AEG. However, the recurrence rate is high when surgery is performed alone. The results of CLASSIC, MAGIC, FLOT4, JCOG0501, PRODIGY, RESOLVE, CROSS trial showed that perioperative chemotherapy and pre- or postoperative chemoradiotherapy significantly increase the overall survival rate and disease free survival rate compared to surgery alone. Radiotherapy and immunotherapy can increase sensitivity to each other, and several clinical studies have also showed that PD-1 antibody may significantly prolongs the life.Thus the investigators plan to conduct this clinical trial to evaluate the effect and safety of concurrent PD-1 antibody-based long-term radiotherapy followed by 2 cycles SOX with PD-1 in patients with locally advanced adenocarcinoma of esophagogastric junction.
Subjects will receive long-term radiotherapy (5w) concurrent with PD-1 antibody for 2 cycles, then receive two cycles of SOX regimen combined PD-1 after a week's rest. Surgery will be performed 2 weeks after the last cycle of neoadjuvant treatment. Adjuvant treatment will be started 3 to 8 weeks after surgery, and SOX regimen will be given for 4 cycles.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenocarcinoma of Esophagogastric Junction
Keywords
PD-1, neoadjuvant therapy, radiotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Neoadjuvant therpy
Arm Type
Experimental
Arm Description
Neoadjuvant chemoradiation plus SOX and PD-1 antibody
Intervention Type
Drug
Intervention Name(s)
neoadjuvant Radiation plus SOX and PD-1 antibody
Other Intervention Name(s)
Neoadjuvant Chemoradiotherapy plus Immunotherapy
Intervention Description
Patients will be given the perioperative treatment as below once recruited:
First, neoradiation (5w) will be given: intensity modulated radiotherapy was given for tumors and high-risk lymphatic drainage areas. PD-1 antibody will be started concurrent the radiation for 2 cycles.
The neochemotherapy (SOX) and PD-1 antibody will be given for 2 cycles after 1 week since radiation completed ; Patients will rest 2 weeks after the last cycle of neochemotherapy, and evaluation will be performed during this time. And D2 surgery will be performed if resectable.
SOX and PD-1 antibody will be given q3w. Adjuvant chemotherapy: We advise starting 4 cycles of SOX regimen in 3-8w after surgery.
Primary Outcome Measure Information:
Title
Pathological Complete Responce (pCR) Rate
Description
Proportion of patients with AEG who received neoadjuvant theray with radiation plus PD-1 antibody and SOX regimen and postoperative pathological examination shows pathological complete responce
Time Frame
Up to 6 months
Secondary Outcome Measure Information:
Title
R0 Resection Rate
Description
Proportion of patients with AEG who received surgery with pathological pathological examination proved microscopically margin-negative resection
Time Frame
Up to 6 months
Title
Progression Free Survival (PFS)
Description
Disease Free Survival was defined as the time from the date of surgery to the date of the local recurrence, and/or distant disease, or tumor-related death.
Time Frame
Up to 3 years
Title
Adverse Events
Description
For any adverse reactions, the researchers refer to the National Cancer Institute (NCI) standard of common toxicity (CTC)
Time Frame
Up to 6 months
Title
Surgery Morbidity
Description
Surgical morbidity reported according to Clavien-Dindo classification
Time Frame
30 days and 12-months after surgery
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed adenocarcinoma of esophagogastric junction, and Her-2 negative.
Clinically diagnosed stage T3+orN+M0, according to CT/MRI scan.
No prior anti-tumor treatment, including surgery, chemotherapy, radiotherapy, and targeted therapy.
Eastern Cooperative Oncology Group(ECOG) performance status(PS) 0-1.
At least one evaluable lesion in abdominal CT/MRI according to RESIST 1.1 is required.
Expected survival ≥6 months.
Adequate organ function, Hemoglobin ≥90g/L; White blood cells ≥3.0×109/L; neutrophil count ≥1.5×109/L; Platelets ≥100×109/L; Serum creatinine (SCr) ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance rate ≥ 50ml/min (Cockcroft-Gault formula); Total bilirubin (TBIL) ≤ 1.5 times the ULN; Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≤ 2.5 times the ULN; Urine protein < 2+; if urine protein ≥ 2+, 24-hour urine protein quantification shows that protein must be ≤ 1 g.
Normal coagulation function, no active bleeding and thrombotic diseases: International Standardized Ratio INR≤1.5×ULN; Partial thromboplastin time APTT≤1.5×ULN; Prothrombin time PT≤1.5ULN;
Previous use of anti-tumor Chinese medicines, proprietary Chinese medicines, and immunomodulators (such as thymosin, interleukin, etc.) must be ≥ 2 weeks from the start of the study medication;
Female patients should not be pregnant or breast feeding. Male should contraception.
Able and willing to give informed consent to participate.
Those who are expected to have good compliance.
Exclusion Criteria:
Existence of other active malignant tumors within 5 years or at the same time.
Already received chemotherapy, radiation therapy, targeted or immunotherapy.
Have any active autoimmune disease or history of autoimmune disease.
Patients with congenital or acquired immunodeficiency.
Use of immunosuppressive drugs within 14 days before the study start.
Administer live attenuated vaccines within 4 weeks before the study start.
Suffering from uncontrolled cardiac clinical symptoms or diseases, such as (1) NYHA II and above heart failure (2) unstable angina pectoris (3) myocardial infarction within 1 year (4) poorly controlled arrhythmia.
Patients with past and current interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, etc., and severely impaired lung function.
Suffering from active pulmonary tuberculosis.
Complicated severe infection within 4 weeks before the the study start, or unexplained fever >38.5°C during the screening period/before the study start.
Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
13. Allergic to any drug in this study. 14. Combined with other severe, acute and chronic diseases that may increase the risk of participating.
15.Participators who had been recruited by other clinical trial within three months.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Liyu Zhu, MD
Phone
+8610-66583821
Email
wcwkzlward@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jing Zhou, MD
Phone
+8610-66583820
Email
wcwkzlward@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yingjiang Ye, MD,PhD
Organizational Affiliation
Peking University People's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking University People's Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100044
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Liyu Zhu
Phone
+8610-66583821
Email
wcwkzlward@163.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Neoadjuvant Immunotherapy and Chemoradiotherapy for Locally Advanced Esophagogastric Junction Adenocarcinoma
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