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

Evaluation of the Efficacy and Safety of Ramucirumab Combined With Nab-paclitaxel, Lobaplatin, and S-1 in Neoadjuvant and Conversion Therapy for Advanced Gastric Cancer (RNPLS-01)

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 and conversion therapy for advanced gastric cancer.

Methods and analysis: This study is a prospective single-center, randomized controlled and open label clinical study containing two cohorts with 140 patients of advanced gastric cancer (Cohort A n=70; Cohort B n=70). The main efficacy indicator is pathological complete response (pCR) of the cancer after neoadjuvant or conversion therapy. The secondary efficacy indicators are R0 resection rate after neoadjuvant or conversion therapy, the incidence of adverse events (AE), progression-free survival (PFS), overall survival (OS), objective response rate (ORR), total response rate and total response time, disease control rate (DCR) and duration of overall response (DOR).

Ethics: Ethics approval has been obtained from the Ethics Committee at the First Affiliated Hospital (Xijing Hospital) of Air force Military Medical University (KY20232220-F-1).

Study Overview

• Status: Recruiting
• Conditions: Advanced Gastric Cancer
• Intervention / Treatment: Drug: nab-paclitaxel, lobaplatin, and S-1 combined with ramucirumab; Drug: nab-paclitaxel, lobaplatin, and S-1

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jianjun Yang, professor; Phone Number: 86+029-84771532; Email: yangjj@fmmu.edu.cn

Study Locations

• China
  • Xi'an, China
    • Recruiting
    • The First Affiliated Hospital of the Air Force Medical University
    • Contact: Jianjun Yang; Phone Number: 029-84771532; Email: yangjj@fmmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ramucirumab combined with lobaplatin, S-1 and nab-paclitaxel; 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: nab-paclitaxel, lobaplatin, and S-1 combined with ramucirumab; Patients in Experimental group will be given ramucirumab (8mg/kg) by intravenous drip on the first day of each cycle, 3 weeks a cycle.; Drug: nab-paclitaxel, lobaplatin, and S-1; 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.
Active Comparator: lobaplatin combined with S-1 and nab-paclitaxel; 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: nab-paclitaxel, lobaplatin, and S-1; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR	pathological complete response	48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection rate	R0 resection rate after neoadjuvant or conversion therapy	48 months
AE	the incidence of adverse events (AE)	48 months
PFS	progression-free survival (PFS)	48 months
OS	overall survival (OS)	48 months
ORR	objective response rate (ORR)	48 months
total response rate	total response rate	48 months
DCR	disease control rate (DCR)	48 months
DOR	duration of overall response (DOR)	48 months
total response time	total response time	48 months

Collaborators and Investigators

• Sponsor: Yang Jianjun, PhD

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 19, 2023
• First Submitted That Met QC Criteria: December 5, 2023
• First Posted (Actual): December 13, 2023

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 20, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: S-1; advanced gastric cancer; nab-Paclitaxel; Ramucirumab; lobaplatin
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Ramucirumab; Albumin-Bound Paclitaxel
• Other Study ID Numbers: RNPLS-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No