chemotherapy combined with apatinib and pd-1 antibody

Conditions: Gastric Cancer

Summary: the effective rate of second-line and later-line single-agent therapy for advanced gastric cancer is limited. this research plan aims to explore whether the combination of drugs can further improve the benefits of second-line and above therapies. previous studies have shown that there is a significant synergistic effect between chemotherapy and pd-1 monoclonal antibody, or anti-angiogenic tki drugs and pd-1 monoclonal antibody. this project is planned to be based on the classic chemotherapy drugs irinotecan or paclitaxel, combined with mesylate apatinib and pd-1 monoclonal antibody, explore the effectiveness and safety of this three-drug combination regimen for the second-line and above treatment of advanced gastric cancer, in order to provide a better late-line treatment plan for patients with advanced gastric cancer.

this study is a prospective, single-center, single-arm phase ii clinical study, which aims to explore the efficacy of pd-1 antibody combined with apatinib combined with chemotherapy as a second-line and above regimen in the treatment of advanced gastric cancer.the enrolled patients were patients with advanced inoperable gastric cancer or gastroesophageal junction adenocarcinoma who had advanced first-line fluorouracil combined with platinum or advanced second-line paclitaxel and irinotecan, with an ecog ps of 0-1. treatment plan: pd-1 antibody: 200mg intravenous drip every 3 weeks; apatinib 250mg/day; chemotherapy: irinotecan 150mg/m2, intravenous drip every 2 weeks, or paclitaxel 150mg/m2, intravenous drip, once every 3 weeks. an imaging evaluation is performed every 6-8 weeks. monitor blood routine, blood biochemistry, electrocardiogram, urine routine, thyroid function, heart function according to clinical routine, and record adverse events. primary observational endpoints: objective effective rate (orr), progression-free survival time (pfs), secondary observational endpoints: overall survival time (os), disease control rate (dcr) and safety, and dynamic monitoring of serum biomolecular markers for exploration study .

Eligibility criteria:
inclusion criteria: patient age ≥18 years old; 1. the ecog score is 0-1 points; 2. patients with locally advanced gastric cancer or gej adenocarcinoma who have been histologically confirmed, metastatic or unresectable; 3. have received at least one systemic chemotherapy regimen in the past and have progressed; or have received adjuvant chemotherapy, but the disease has progressed or relapsed within 6 months after the end of the treatment; have not used any of the drug treatments in this study; 4. there are measurable lesions that meet the recist 1.1 standard; 5. it has sufficient organ and bone marrow function, and the laboratory examination meets the following requirements: a.hgb≥90g/l;b.neut≥1.5×109/l;c.plt ≥100×109/l;d. bil≤1.5 times the upper limit of normal (uln);e. alt and ast≤2.5×uln; liver metastasis, then alt and ast≤5×uln;f. endogenous creatinine clearance rate ≥50ml/min (cockcroft-gault formula);g. urine routine is normal, or urine protein \<(++), or 24-hour urine protein \<1.0 g; 6. normal blood coagulation, no active bleeding and thrombosis: a. international normalized ratio inr≤1.5;b. partial thromboplastin time aptt≤1.5 uln; 7. women of childbearing age must undergo a negative pregnancy test (serum or urine) within 14 days before enrollment, and voluntarily use appropriate methods of contraception during the observation period and within 8 weeks after the last administration of the study drug; for men, it should be surgery sterilize or agree to use appropriate methods of contraception during the observation period and within 8 weeks after the last administration of the study drug; 8. estimated survival period ≥ 3 months; 9. the patient voluntarily joined the study and signed an informed consent form (icf);those who are expected to have good compliance can follow up the efficacy and adverse reactions as required by the protocol. exclusion criteria: 1. have received anti-angiogenesis drug therapy in the past; 2. have received anti-pd-1 and anti-pd-l1 antibody drug therapy in the past; 3. patients with high blood pressure who cannot be reduced to the normal range by antihypertensive drugs (systolic blood pressure\>140 mmhg, diastolic blood pressure\>90 mmhg), coronary heart disease above grade i, grade i arrhythmia (including qtc interval prolongation) male\>450 ms, female\>470 ms) and grade i cardiac insufficiency; 4. there are many factors that affect oral drugs (such as inability to swallow and intestinal obstruction, etc.); 5. allergic to the drugs in this program; 6. patients with a clear gastrointestinal bleeding tendency, including the following conditions: local active ulcer lesions, and fecal occult blood (+ +) cannot be included in the group; patients with a history of melena and hematemesis within 1 month; 7. patients with contraindications to apatinib: for patients with active bleeding, intestinal perforation, intestinal obstruction, within 30 days after major surgery, drug-uncontrollable hypertension, grade ⅲ-ⅳ cardiac insufficiency (nyha standard), severe liver and kidney patients with dysfunction (grade 4); if you have immune system diseases, you need to use a daily dose of dexamethasone above 10mg; 8. according to the judgment of the investigator, patients with concomitant diseases that seriously endanger the safety of the patient or affect the completion of the study; 9. the researcher believes that it is not suitable for inclusion.

Keywords: gastric cancer second-line treatment chemotherapy apatinib mesylate immunotherapy pd-1 antibody