Clinical trial NCT06739161: Sintilimab in Combination with Chemotherapy ± Local Treatment for Om-G/GEJ
Official title: A Phase II Randomized Controlled Trial of Sintilimab in Combination with Chemotherapy ± Local Treatment for Oligometastatic Esophagogastric Junction/Gastric Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Gastroesophageal Junction Adenocarcinoma
Lead sponsor: Jiangsu Cancer Institute & Hospital
Sponsor class: OTHER
First posted: 2024-12-18
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Pathologically confirmed esophagogastric junction (EGJ)/gastric adenocarcinoma.
2. 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.
3. No progression after two cycles of immunochemotherapy.
4. Primary and metastatic lesions at diagnosis eligible for local treatment.
5. All metastatic lesions measurable per RECIST 1.1.
6. Adequate hematological function: Neutrophil count ≥ 1.5 × 109/L, Platelets ≥ 100 × 109/L and Hemoglobin ≥90g/L.
7. 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.
8. Adequate renal function: Serum creatinine ≤ 1.5 x ULN, and creatinine clearance ≥ 60 ml/min.
9. Adequate coagulation function: INR/PT≤ 1.5 x ULN, aPTT≤ 1.5 x ULN.
10. No serious concomitant disease that will threaten the survival of patients to less than 5 years.
11. Male or female. Age ≥ 18 years and ≤80 years.
12. Written (signed) informed consent.
13. Good compliance with the study procedures, including lab and auxiliary examination and treatment.
14. Female patients should not be pregnant or breast feeding.

Exclusion Criteria:

1. Non-adenocarcinoma histology of gastric/esophagogastric junction tumors, such as squamous cell carcinoma or neuroendocrine carcinoma.
2. Esophagogastric junction/gastric adenocarcinoma with positive Her-2 status requiring anti-Her-2 treatment.
3. Uncontrolled meningeal or peritoneal metastasis.
4. Peripheral neuropathy of grade ≥2.
5. Poor nutritional status, BMI \<18.5 kg/m², or PG-SGA score ≥9.
6. Underwent major surgery or suffered a severe injury within 4 weeks prior to the first dose of the investigational drug.
7. Presence of uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
8. Received any investigational drug within 4 weeks prior to the first dose of the study drug.
9. 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.
10. Received an anti-tumor vaccine or live vaccine within 4 weeks before the first dose of the study drug.
11. Diagnosed with any active autoimmune disease or a history of autoimmune diseases.
12. History of immunodeficiency, including a positive HIV test, any acquired or congenital immunodeficiency diseases, or a history of organ transplantation or allogeneic bone marrow transplantation.
13. Any condition within 14 days prior to treatment requiring systemic corticosteroid therapy (dose\>10mg/day of prednisone or equivalent) or other immunosuppressive treatments.
14. Presence of uncontrolled cardiac symptoms or conditions, such as:

    * NYHA Class II or higher heart failure
    * Unstable angina
    * Myocardial infarction within the past year
    * Clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention.
15. Severe infection within 4 weeks prior to the first dose, including pneumonia requiring hospitalization, bacteremia, or infectious complications.
16. History of interstitial lung disease, non-infectious pneumonia, pulmonary fibrosis, or other uncontrolled acute pulmonary diseases.
17. Active pulmonary tuberculosis infection diagnosed by history or CT scan, or a history of active tuberculosis infection within the past year, or a history of untreated active tuberculosis infection more than one year ago.
18. Active hepatitis B or hepatitis C.
19. Laboratory abnormalities of sodium, potassium, or calcium greater than Grade 1 within 2 weeks before enrollment that cannot be corrected with treatment.
20. Known allergy to monoclonal antibodies, any PD-1 components, paclitaxel, capecitabine, or any components used in their formulations.
21. Pregnant or breastfeeding women, or women of childbearing potential who are unwilling or unable to use effective contraception.

Primary outcomes:
measure: Progression free survival, defined as the time from randomization to disease progression or death, whichever occurs first.
timeFrame: From the date of randomization until tumor progression or death from any cause, whichever occurs first, assessed up to 24 months
Secondary outcomes:
measure: Overall Survival, defined as the time from randomization to death from any cause.
timeFrame: From the date of randomization until death from any cause, assessed up to 36 months
measure: Objective Response Rate, defined as the proportion of participants achieving a complete or partial response, as assessed by RECIST v1.1 criteria.
timeFrame: From the date of randomization until the date of first documented objective response, assessed up to 12 months
measure: Time to Progression, defined as the time from randomization to the first documented disease progression, as assessed by RECIST v1.1 criteria.
timeFrame: From the date of randomization until the date of first documented progression, assessed up to 24 months
measure: Treatment Safety: Number of participants with treatment-related adverse events, as assessed by CTCAE v5.0.
timeFrame: From the date of randomization until the end of treatment, assessed up to 18 months
measure: Time to Symptom Deterioration, based on patient-reported outcomes using validated quality of life instruments (e.g., EORTC QLQ-C30).
timeFrame: From the date of randomization until the first documented symptom deterioration, assessed up to 12 months
Other outcomes:
Locations:
city: Nanjing
country: China
facility: ChengChen
state: Jiangsu
Study officials:
affiliation: Jiangsu Cancer Institute & Hospital
name: Cheng Chen
role: PRINCIPAL_INVESTIGATOR
References: