Combination of chemotherapy and immunotherapy for advanced esophagogastric junction cancer

Perioperative SOX Plus Sintilimab Compared With Perioperative SOX in the Locally Advanced Esophagogastric Junction Adenocarcinoma: an Open-label, Phase 2 Randomised Controlled Trial

This study is testing if combining a new immune therapy with chemotherapy can help people with advanced esophagogastric junction cancer have smaller tumors that are easier to remove and improve their chances of living longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 302 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University (Academic / other)
• Drugs / interventions: radiation, prednisone, Sintilimab, chemotherapy, Sinitilimab
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT04989985 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of combining the anti-PD-1 antibody sintilimab with perioperative chemotherapy (SOX: oxaliplatin plus S-1) in patients with locally advanced adenocarcinoma of the esophagogastric junction. The goal is to downstage the tumor, improve resectability, and enhance long-term survival rates. The study is multi-center, open-label, and randomized, focusing on the tolerability, safety, and efficacy of this novel treatment approach. Participants will undergo treatment followed by surgery to assess outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with histologically confirmed locally advanced esophagogastric junction adenocarcinoma and good overall health.

Not a fit: Patients with contraindications for surgery or those with severe comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates and reduce recurrence in patients with advanced esophagogastric junction cancer.

How similar studies have performed: Other studies have shown promising results with similar combinations of chemotherapy and PD-1 inhibitors in various cancers, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Written (signed) informed consent;
2. Histologically CT/MRI confirmed cT3-4aN+M0 Esophagogastric Junction Adenocarcinoma;
3. Consent to send tumor tissue from biopsy or resection for PD-L1, EBV, MSI detection;
4. Female or male, 18-75 years;
5. ECOG 0-1, no surgery contraindications;
6. Physical condition and adequate organ function to ensure the success of abdominal and/or thoracic surgery;
7. Expected survival ≥ 6 months;
8. Adequate hematological, liver, renal and coagulation function; 1) Platelet (PLT) count ≥100,000 /mm3; 2) White Blood cell（WBC）count ≥4,000 /mm3 and ≤15,000 /mm3 ；Neutrophil count (ANC) ≥1,500 /mm3; 3) Hemoglobin (Hb) level ≥9.0 g/dl; 4) International normalized ratio (INR) ≤1.5; 5) Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5×ULN; 6) Glycosylated hemoglobin (HbA1c) \<7.5%; 7) Total bilirubin (TBIL) level ≤1.5×ULN; 8) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level ≤2.5×ULN (≤5×ULN in case of liver metastasis); 9) Alkaline phosphatase level ≤2.5×ULN (≤5×ULN in case of liver metastasis); 10) Serum creatinine (Cr) level ≤1.5×ULN and creatinine clearance ≥60 ml/min;
9. Patients with Good compliance, who can cooperate with the laboratory, auxiliary examinations and corresponding specimen collection of this program set;
10. Females of child bearing age must have a negative pregnancy test, and have to take contraception measures and avoid breast feeding during the study and for 6 months after the last dose; male subjects must agree to taken contraception measures during the study and for 6 months after the last dose.

Exclusion Criteria:

1. Suffer from other active malignant tumors within 5 years or at the same time. Cured localized tumors, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, prostate carcinoma in situ, cervical carcinoma in situ, breast carcinoma in situ, etc. can be included in the group.
2. Patients who are planning to undergo or have previously received organ or bone marrow transplantation.
3. Myocardial infarction or poorly controlled arrhythmia (including QTc interval ≥ 450 ms for males and ≥ 470 ms for females) occurred within 6 months before the first medication (QTc interval is calculated by Fridericia's formula).
4. There is NYHA standard grade III to IV cardiac insufficiency or color Doppler ultrasound examination: LVEF (left ventricular ejection fraction) \<50%.
5. Human immunodeficiency virus (HIV) infection.
6. Suffer from active tuberculosis.
7. Past and present patients who have interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severely impaired lung function, etc., which may interfere with the detection and management of suspected drug-related lung toxicity.
8. There is a known active or suspicious autoimmune disease. Except those who were in a stable state of the disease at the time of enrollment (no need for systemic immunosuppressive therapy).
9. Received treatment with live vaccine within 28 days before the first administration; except for the treatment of seasonal influenza with inactivated viral vaccine.
10. Patients who need to receive systemic corticosteroids (\> 10 mg/day curative dose of prednisone) or other immunosuppressive drugs within 14 days before the first medication or during the study period. However, the following conditions are allowed to enter the group: in the absence of active autoimmune diseases, patients are allowed to use topical or inhaled steroids, or adrenal hormone replacement therapy with a dose of ≤ 10 mg/day prednisone.
11. Any active infection that requires systemic anti-infective treatment occurs within 14 days before the first administration of the drug; except for receiving preventive antibiotic treatment (such as prevention of urinary tract infection or chronic obstructive pulmonary disease).
12. Have received other antibody/drug treatments for immune checkpoints in the past, such as PD-1, PD-L1, CTLA4 and other treatments.
13. Are receiving other clinical research treatments, or the planned start of this research treatment is less than 14 days from the end of the previous clinical research treatment.
14. Known to have a history of severe allergies to any monoclonal antibodies or study drug excipients.
15. Known history of psychotropic drug abuse or drug use; patients who have stopped drinking can be included in the group.
16. There are patients who may increase the risk of participating in research and research medication, or other severe, acute and chronic diseases, who are not suitable for participating in clinical research based on the judgment of the investigator.

Where this trial is running

Guangzhou, Guangdong

• The sixth affiliated hospital of Sun Yat-sen University — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Jun-Sheng Peng, Dr — Sixth Affiliated Hospital, Sun Yat-sen University
• Study coordinator: Jun-Sheng Peng

Conditions Locally Advanced Gastroesophageal Junction Adenocarcinoma; Chemotherapy Effect; sinitilimab; SOX; peri-operative chemotherapy