Neoadjuvant Immunotherapy and Chemoradiotherapy for Locally Advanced Esophagogastric Junction Adenocarcinoma (NICLA)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Adenocarcinoma of Esophagogastric Junction
• Intervention / Treatment: Drug: neoadjuvant Radiation plus SOX and PD-1 antibody

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.

• Study Type: Interventional
• Enrollment (Anticipated): 26
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Liyu Zhu, MD; Phone Number: +8610-66583821; Email: wcwkzlward@163.com
• Study Contact Backup: Name: Jing Zhou, MD; Phone Number: +8610-66583820; Email: wcwkzlward@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Peking University People's Hospital
      • Contact: Liyu Zhu; Phone Number: +8610-66583821; Email: wcwkzlward@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically confirmed adenocarcinoma of esophagogastric junction, and Her-2 negative.
2. Clinically diagnosed stage T3+orN+M0, according to CT/MRI scan.
3. No prior anti-tumor treatment, including surgery, chemotherapy, radiotherapy, and targeted therapy.
4. Eastern Cooperative Oncology Group(ECOG) performance status(PS) 0-1.
5. At least one evaluable lesion in abdominal CT/MRI according to RESIST 1.1 is required.
6. Expected survival ≥6 months.
7. 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.
8. 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;
9. 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;
10. Female patients should not be pregnant or breast feeding. Male should contraception.
11. Able and willing to give informed consent to participate.
12. Those who are expected to have good compliance.

Exclusion Criteria:

1. Existence of other active malignant tumors within 5 years or at the same time.
2. Already received chemotherapy, radiation therapy, targeted or immunotherapy.
3. Have any active autoimmune disease or history of autoimmune disease.
4. Patients with congenital or acquired immunodeficiency.
5. Use of immunosuppressive drugs within 14 days before the study start.
6. Administer live attenuated vaccines within 4 weeks before the study start.
7. 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.
8. Patients with past and current interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, etc., and severely impaired lung function.
9. Suffering from active pulmonary tuberculosis.
10. 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.
11. 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.

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: Neoadjuvant therpy; Neoadjuvant chemoradiation plus SOX and PD-1 antibody

Drug: neoadjuvant Radiation plus SOX and PD-1 antibody; 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.; Other Names: Neoadjuvant Chemoradiotherapy plus Immunotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	For any adverse reactions, the researchers refer to the National Cancer Institute (NCI) standard of common toxicity (CTC)	Up to 6 months
R0 Resection Rate	Proportion of patients with AEG who received surgery with pathological pathological examination proved microscopically margin-negative resection	Up to 6 months
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.	Up to 3 years
Surgery Morbidity	Surgical morbidity reported according to Clavien-Dindo classification	30 days and 12-months after surgery

Collaborators and Investigators

• Sponsor: Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2023
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): December 1, 2027

Study Registration Dates

• First Submitted: August 15, 2022
• First Submitted That Met QC Criteria: August 15, 2022
• First Posted (Actual): August 17, 2022

Study Record Updates

• Last Update Posted (Actual): August 17, 2022
• Last Update Submitted That Met QC Criteria: August 15, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: PD-1, neoadjuvant therapy, radiotherapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: WCWKZL-001

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