A Phase II Randomized Controlled Trial of Sintilimab in Combination with Chemotherapy ± Local Treatment for Oligometastatic Esophagogastric Junction/Gastric Adenocarcinoma
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Gastroesophageal Junction Adenocarcinoma
- Sponsor
- Jiangsu Cancer Institute & Hospital
- Enrollment
- 120
- Locations
- 1
- Primary Endpoint
- Progression free survival, defined as the time from randomization to disease progression or death, whichever occurs first.
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
Gastric cancer is one of the most common and deadly cancers globally, with poor prognosis. About 70% of patients are diagnosed at an advanced stage, and the median overall survival (OS) is only 3-4 months. Current treatments, including immune checkpoint inhibitors combined with chemotherapy, have slightly improved survival, but most patients still experience disease progression during treatment, and those with PD-L1 CPS ≤5 do not benefit from immunotherapy.
Local radiotherapy, as a palliative treatment, can alleviate symptoms like bleeding, dysphagia, and pain, improving quality of life. Studies show that it significantly improves progression-free survival and may extend overall survival when added to chemotherapy. Therefore, combining local radiotherapy with immunochemotherapy may offer additional survival benefits for patients with advanced gastric cancer.
Investigators
Cheng Chen
Principal Investigator
Jiangsu Cancer Institute & Hospital
Eligibility Criteria
Inclusion Criteria
- •Pathologically confirmed esophagogastric junction (EGJ)/gastric adenocarcinoma.
- •Oligometastatic disease diagnosed via CT, MRI, or PET/CT:≤3 extracranial organs involved, ≤5 total metastatic lesions, each ≤5 cm in diameter,Regional lymph nodes count as one station; distant nodes counted per station.
- •No progression after two cycles of immunochemotherapy.
- •Primary and metastatic lesions at diagnosis eligible for local treatment.
- •All metastatic lesions measurable per RECIST 1.
- •Adequate hematological function: Neutrophil count ≥ 1.5 × 109/L, Platelets ≥ 100 × 109/L and Hemoglobin ≥90g/L.
- •Adequate liver function: Total bilirubin ≤ 1.5 × upper limit of normal (ULN); AST (SGOT) and ALT (SGPT) \< 2.5 × ULN in the absence of liver metastases, or \< 5 × ULN in case of liver metastases. ALP ≤ 2.5 × upper limit of normal (ULN); ALB ≥30g/L.
- •Adequate renal function: Serum creatinine ≤ 1.5 x ULN, and creatinine clearance ≥ 60 ml/min.
- •Adequate coagulation function: INR/PT≤ 1.5 x ULN, aPTT≤ 1.5 x ULN.
- •No serious concomitant disease that will threaten the survival of patients to less than 5 years.
Exclusion Criteria
- •Non-adenocarcinoma histology of gastric/esophagogastric junction tumors, such as squamous cell carcinoma or neuroendocrine carcinoma.
- •Esophagogastric junction/gastric adenocarcinoma with positive Her-2 status requiring anti-Her-2 treatment.
- •Uncontrolled meningeal or peritoneal metastasis.
- •Peripheral neuropathy of grade ≥
- •Poor nutritional status, BMI \<18.5 kg/m², or PG-SGA score ≥
- •Underwent major surgery or suffered a severe injury within 4 weeks prior to the first dose of the investigational drug.
- •Presence of uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
- •Received any investigational drug within 4 weeks prior to the first dose of the study drug.
- •Required systemic treatment with corticosteroids (daily \>10 mg prednisone equivalent) or other immunosuppressive agents within 2 weeks prior to the first dose of the investigational drug.
- •Received an anti-tumor vaccine or live vaccine within 4 weeks before the first dose of the study drug.
Outcomes
Primary Outcomes
Progression free survival, defined as the time from randomization to disease progression or death, whichever occurs first.
Time Frame: From the date of randomization until tumor progression or death from any cause, whichever occurs first, assessed up to 24 months
Progression will be assessed based on imaging studies and clinical evaluation, using RECIST v1.1 criteria. Data will be summarized using Kaplan-Meier estimates, and hazard ratios will be calculated.
Secondary Outcomes
- Overall Survival, defined as the time from randomization to death from any cause.(From the date of randomization until death from any cause, assessed up to 36 months)
- Objective Response Rate, defined as the proportion of participants achieving a complete or partial response, as assessed by RECIST v1.1 criteria.(From the date of randomization until the date of first documented objective response, assessed up to 12 months)
- Time to Progression, defined as the time from randomization to the first documented disease progression, as assessed by RECIST v1.1 criteria.(From the date of randomization until the date of first documented progression, assessed up to 24 months)
- Treatment Safety: Number of participants with treatment-related adverse events, as assessed by CTCAE v5.0.(From the date of randomization until the end of treatment, assessed up to 18 months)
- Time to Symptom Deterioration, based on patient-reported outcomes using validated quality of life instruments (e.g., EORTC QLQ-C30).(From the date of randomization until the first documented symptom deterioration, assessed up to 12 months)