Ramucirumab Combined With Nab-paclitaxel, Lobaplatin, and S-1 in Neoadjuvant Transformation Therapy for Advanced Gastric Cancer

Study Overview
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Brief Summary
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Abstract Objective: Ramucirumab is a VEGFR2 antagonist. The aim of this trial is to evaluate the efficacy and safety of Ramucirumab combined with nab-Paclitaxel, lobaplatin and S-1 in neoadjuvant or transformational therapy for advanced gastric cancer. Methods and analysis: This study is a prospective single-center and case-control clinical study containing three cohorts with 48 patients of advanced gastric cancer (Cohort A n=12; Cohort B n=12; Cohort C n=24). The main efficacy indicators are pathological response grading (TRG), R0 resection rate after neoadjuvant or conversion therapy, pathological complete response (pCR) of the tumor after neoadjuvant or conversion therapy and the incidence of adverse events (AE). The secondary efficacy indicators are progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and disease response time (DOR). Ethics and dissemination: Ethics approval has been obtained from the Ethics Committee at the First Affiliated Hospital (Xijing Hospital) of Fourth Military Medical University (KY20232220-F-1). The results of this study will be disseminated at several research conferences and as published articles in peer-reviewed journals.

Official Title
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Evaluation of the Efficacy and Safety of Ramucirumab Combined With Nab-paclitaxel, Lobaplatin, and S-1 in Neoadjuvant Transformation Therapy for Advanced Gastric Cancer: a Study Protocol of Prospective Single-center and Case-control Clinical Trial (RNPLS-01)

Conditions
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Advanced Gastric Cancer

Intervention / Treatment
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* Drug: Ramucirumab
* Drug: lobaplatin, S-1 and nab-paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cohort A: Patients are diagnosed with locally advanced gastric or gastroesophageal junction adenocarcinoma by cytology or histopathology and in need of preoperative neoadjuvant therapy to reduce recurrence and metastasis rates; Cohort B: Patients with advanced gastric cancer who have undergone surgery after neoadjuvant chemotherapy with previously used nab-paclitaxel, lobaplatin and S-1. Patients are adults aged 18-75 years with an Eastern Cooperative Oncology Group(ECOG) performance status score less than or equals to 1. Have not received anti-tumor treatment (such as surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy) . Functions of the major organs and bone marrow meet the following criteria within 7 days before treatment: hemoglobin ≥ 80g/L, absolute neutrophil count ≥ 1.5 × 109/L, platelet (PLT) ≥ 100× 109/L, without blood transfusion within 14 days, total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5x ULN or if complicated with liver metastasis then ALT and AST ≤ 5x ULN, serum creatinine ≤ 1.5x ULN or creatinine clearance ≥ 50mL/min or urinary protein<2+, activated partial thromboplastin time (APTT) and international standardized ratio (INR)≤1.5×ULN. Expected lifespan ≥ 6 months. The patients are able and willing to provide written informed consent to participate in the study. Exclusion Criteria: Patients who have previously suffered from other malignant tumors, except for cured skin basal cell carcinoma and cervical carcinoma in situ. HER-2 positive patients who are willing to receive Herceptin treatment. Women who are pregnant or lactating or in the reproductive period and have not taken effective contraceptive measures, or those who have fertility requirements during the research period. Patients with serious and uncontrolled internal diseases and infections or with chronic bowel disease or short bowel syndrome. Patients with major organ failure, such as compensatory heart, lung, liver, and kidney failure as well as severe metabolic abnormalities in liver and kidney which affects normal drug metabolism. Patients with a clear tendency for gastrointestinal bleeding and/or abnormal coagulation function (INR>1.5)under researchers evaluation. hepatitis B virus or hepatitis C virus in active phase Patients with peripheral neuropathy neoadjuvant chemotherapy(NCT)-CTCAE ≥ Level 2. -

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ramucirumab combined with lobaplatin, S-1 and nab-paclitaxel<br>Patients will be given ramucirumab (8mg/kg), lobaplatin (30 mg/m2) and nab-paclitaxel (100mg/m2) by intravenous drip on the first day of each cycle, 3 weeks a cycle, together with oral S-1 (patients with a body surface area less than 1.25 m2, will give 40 mg each time; patients with a body surface area between 1.25 and 1.5 m2; will give 50 mg each time; patients with a body surface area greater than 1.5 m2, will give 60 mg each time), 2 weeks on and 1 week off. | Drug: Ramucirumab<br>* Patients in Experimental group will be given ramucirumab (8mg/kg) by intravenous drip on the first day of each cycle, 3 weeks a cycle.<br>Drug: lobaplatin, S-1 and nab-paclitaxel<br>* Patients will be given lobaplatin (30 mg/m2) and nab-paclitaxel (100mg/m2) by intravenous drip on the first day of each cycle, 3 weeks a cycle, together with oral S-1 (patients with a body surface area less than 1.25 m2, will give 40 mg each time. Patients with a body surface area between 1.25 and 1.5 m2; will give 50 mg each time; patients with a body surface area greater than 1.5 m2, will give 60 mg each time), 2 weeks on and 1 week off.<br>|
| Active Comparator: lobaplatin combined with S-1 and nab-paclitaxel<br>Patients will be given lobaplatin (30 mg/m2) and nab-paclitaxel (100mg/m2) by intravenous drip on the first day of each cycle, 3 weeks a cycle, together with oral S-1 (patients with a body surface area less than 1.25 m2, will give 40 mg each time; patients with a body surface area between 1.25 and 1.5 m2; will give 50 mg each time; patients with a body surface area greater than 1.5 m2, will give 60 mg each time), 2 weeks on and 1 week off. | Drug: lobaplatin, S-1 and nab-paclitaxel<br>* Patients will be given lobaplatin (30 mg/m2) and nab-paclitaxel (100mg/m2) by intravenous drip on the first day of each cycle, 3 weeks a cycle, together with oral S-1 (patients with a body surface area less than 1.25 m2, will give 40 mg each time. Patients with a body surface area between 1.25 and 1.5 m2; will give 50 mg each time; patients with a body surface area greater than 1.5 m2, will give 60 mg each time), 2 weeks on and 1 week off.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TRG | pathological response grading | 48 months | 
| R0 resection rate | R0 resection rate after neoadjuvant or conversion therapy | 48 months | 
| pCR | pathological complete response of the tumor after neoadjuvant or conversion therapy | 48 months | 
| AE | incidence of adverse events | 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | progression-free survival | 48 months | 
| OS | overall survival | 48 months | 
| ORR | objective response rate | 48 months | 
| DCR | disease control rate | 48 months | 
| DOR | disease response time | 48 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ramucirumab, nab-Paclitaxel, lobaplatin, S-1, advanced gastric cancer