Chemotherapy Combined With Apatinib and PD-1 Antibody

Study Overview
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Brief Summary
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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.

Detailed Description
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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 .

Official Title
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Chemotherapy Combined With Apatinib and PD-1 Monoclonal Antibody for Second-line or Above Treatment of Advanced Gastric Cancer-A Prospective, Single-arm, Open, Phase II Study

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: PD-1 antibody, paclitaxel or irinotecan, Apatinib mesylate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient age ≥18 years old; The ECOG score is 0-1 points; Patients with locally advanced gastric cancer or GEJ adenocarcinoma who have been histologically confirmed, metastatic or unresectable; 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; There are measurable lesions that meet the RECIST 1.1 standard; 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; Normal blood coagulation, no active bleeding and thrombosis: a. International normalized ratio INR≤1.5;b. Partial thromboplastin time APTT≤1.5 ULN; 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; Estimated survival period ≥ 3 months; 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: Have received anti-angiogenesis drug therapy in the past; Have received anti-PD-1 and anti-PD-L1 antibody drug therapy in the past; 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; There are many factors that affect oral drugs (such as inability to swallow and intestinal obstruction, etc.); Allergic to the drugs in this program; 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; 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; 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; The researcher believes that it is not suitable for inclusion.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PD-1 antibody combined with apatinib and chemotherapy<br>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. | Drug: PD-1 antibody, paclitaxel or irinotecan, Apatinib mesylate<br>* 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.<br>* Other names: PD-1 antibody, chemotherapy,Apatinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Overall Response Rate | The proportion of CR and PR | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 
| Progression Free Survival | Time from the start of treatment to the progression of the disease | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Time from the start of treatment to the occurrence of death | From date of randomization until the date of death from any cause or the last visit date, whichever came first, assessed up to 60 months | 
| Disease Control rate | The proportion of CR,PR and SD | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 
| adverse events | The incidence of various adverse events | Until 3 months after the end of the treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Apatinib mesylate, immunotherapy, PD-1 antibody, gastric cancer, second-line treatment, chemotherapy