conversion therapy of sintilimab in combination with fruquintinib and chemotherapy versus sintilimab and chemotherpay in stage iv gastric cancer

Conditions: Gastric Cancer; Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma

Summary: this is a multicenter, randomized, open-label, phase 2 clinical study aiming to evaluate the feasibility and efficacy of sintilimab (pd-1 inhibitor) in combination of fruquintinib and chemotherapy (s-1 plus nab-paclitaxel) versus sintilimab and chemotherapy as conversion therapy in patients with stage iv gastric cancer in china.


Eligibility criteria:
inclusion criteria: * histologically confirmed gastric/gastroesophageal junction adenocarcinoma through gastroscopy. * ages: 18-70 years (concluding 18 and 70 years) * life expectancy ≥3 months. * treatment-naive stage iv (clinical staging, ajcc 8th) unresectable patients, no prior antitumor therapy (including radiation, chemotherapy, targeted therapy or immunotherapy, etc.). * the eastern cooperative oncology group performance status (ecog ps) of 0-1. * preoperative examinations using ct, mri, pet-ct, etc., indicating only one unresectable factor or peritoneal metastasis with another unresectable factor, such as: 1. n3 lymph node metastasis, mainly referring to group 16 lymph node metastasis. 2. extensive or bulky lymph nodes (d2) 3. locally advanced t4b. 4. hepatic metastases (h1): ≤5 lesions with a total diameter ≤8cm. 5. peritoneal metastasis (cy1, p1). 6. ovarian metastasis (krukenberg tumor). * physically fit for major abdominal surgery. * adequate organ and marrow function, defined as: 1. hematological status: absolute neutrophil count (anc) ≥1.5×10\^9/l; platelet count (plt) ≥100×10\^9/l; hemoglobin (hgb) ≥9.0 g/dl. 2. liver function: for patients without liver metastasis, serum total bilirubin (tbil) ≤1.5× upper limit of normal (uln); alt and ast ≤2.5×uln. for patients with liver metastasis: tbil ≤1.5×uln; alt and ast ≤5×uln. 3. renal function: creatinine clearance (ccr) ≥50 ml/min (calculated using the cockcroft/gault formula). * adequate coagulation function, defined as international normalized ratio (inr) or prothrombin time (pt) ≤1.5 times uln. * voluntary participation and signed informed consent with expected good compliance and follow-up. * not involved in other clinical trials. * willing to provide blood and histological samples. * no serious conditions affecting anesthesia, or surgery. * no hematologic disorders affecting postoperative hemoglobin levels. exclusion criteria: * has distal metastases other than oligometastases as defined in the inclusion criteria, such as pulmonary metastases, brain metastases, bone metastases, etc. * her-2 positive patients or willing to receive trastuzumab. * endoscopic signs of active bleeding from the lesion. * patients with moderate/large volume of ascites. * near-obstruction at the cardia or pylorus affecting feeding and gastric emptying or difficulty swallowing tablets. * concurrently suffering from other serious illnesses that are difficult to control (severe uncontrolled recurrent infections, atrial fibrillation, angina pectoris, cardiac insufficiency, ejection fraction measurement under 50%, uncontrolled hypertension, renal insufficiency, symptomatic peripheral neuropathy, and nci classification \>ii) * has already on other medications prior to enrollment or could not be assured of compliance after enrollment. * allergy to any drugs in the regimen. * women who are pregnant or breastfeeding and have childbearing potential but are not taking adequate contraceptive measures. * organ transplant recipients requiring immunosuppression. * patients without decision-making capacity or with psychiatric disorders. * systemic treatment with chinese herbal anti-tumor or immunomodulatory drugs (including thymosin, interferons, interleukins) within 2 weeks before the first dose. * use of immunosuppressive drugs within 4 weeks before the first study treatment, excluding local steroids or physiological doses of systemic steroids. * has received a live or live-attenuated vaccine within 30 days prior to the first dose of study treatment. * has a diagnosis of autoimmune disease within the previous 2 years (patients with vitiligo, psoriasis, alopecia areata, or graves' disease who do not require systemic therapy within the last 2 years, hypothyroidism requiring only thyroid hormone replacement therapy, and type i diabetes mellitus requiring only insulin replacement therapy are eligible for enrollment). * known history of primary immunodeficiency. * known to have active tuberculosis. * has history of human immunodeficiency virus (hiv) infection (i.e., hiv antibody . positive); untreated acute or chronic active hepatitis b or hepatitis c infection. patients receiving antiretroviral therapy are eligible for enrollment on an individual basis as determined by the physician with monitoring of viral copy number. * urinalysis indicating urine protein ≥2+ and 24-hour urine protein quantification \>1.0g.