A Study on the Combination of Sintilimab, Ramucirumab and Chemotherapy for First-line Treatment of Gastric Cancer With Liver Metastasis

Sintilimab Combined With Ramucirumab and Chemotherapy as First-line Treatment in Patients With Advanced Gastric Cancer With Liver Metastasis (RAMSINT): A Phase II, Single-center, Prospective Clinical Study

The goal of this clinical trial is to observe the efficacy and safety of Sintilimab (a PD-1 inhibitor) combined with Ramucirumab (a VEGFR-2 antagonist) and chemotherapy as a first-line treatment for patients with advanced gastric cancer with liver metastasis.

• Can the combination of Sintilimab, Ramucirumab, and chemotherapy improve the prognosis of patients with AGC and liver metastases?
• What are the adverse events (AEs) associated with the use of the combination regimen of Sintilimab, Ramucirumab, and chemotherapy in patients with AGC and liver metastases?

Participants will:

• Receive a combined treatment regimen of Sintilimab, Ramucirumab, and chemotherapy (SOX (oxaliplatin and S-1) or XELOX (oxaliplatin and capecitabine)), administered every 21 days for up to 6 cycles. Following the completion of 6 cycles, maintenance therapy with Sintilimab and oral chemotherapy agents (capecitabine or S-1) with or without Ramucirumab will be administered until disease progression.
• Imaging assessments will be performed at baseline, after every 2 cycles of treatment, and every 3 months following the completion of 6 cycles of treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Stomach Neoplasms
• Intervention / Treatment: Drug: Sintilimab; Drug: Ramucirumab; Drug: SOX/XELOX

• Study Type: Interventional
• Enrollment (Estimated): 39
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hao Wu; Phone Number: 86-13913855335; Email: whdactor@njmu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Voluntary participation in the clinical study; full understanding and informed consent to this study by signing the Informed Consent Form (ICF); willingness to follow and ability to complete all trial procedures.
2. Patients with histologically or cytologically confirmed, unresectable, or who refuse surgical resection of locally advanced, recurrent, or metastatic gastric and gastroesophageal junction (GEJ) adenocarcinoma (including signet-ring cell carcinoma, mucinous adenocarcinoma, hepatoid adenocarcinoma, etc.). (Note: For patients who relapse after neoadjuvant/adjuvant therapy, the time from the end of neoadjuvant/adjuvant therapy to disease relapse must be more than 6 months.)
3. Patients, except those with recurrent disease after neoadjuvant/adjuvant therapy, must not have previously received systemic treatment.
4. Participants must be histologically confirmed as having HER2-negative gastric cancer, GEJ cancer, or esophageal adenocarcinoma.
5. There must be at least one measurable lesion in the liver assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) that can undergo repeat radiological evaluation; the radiological tumor assessment should be performed within 28 days prior to randomization.
6. The Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-2 within 7 days prior to the first dose of medication.
7. Availability of representative tumor tissue specimens, blood samples, and fecal samples for exploratory research.
8. Main organ functions must be normal, meeting the following criteria:

Liver Function Alanine Aminotransferase (ALT) ≤5.0 × ULN Aspartate Aminotransferase (AST) ≤5.0 × ULN

Exclusion Criteria:

1. History of other active malignancies within the past 5 years or currently having other active malignancies. Treated localized tumors, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, prostate carcinoma in situ, cervical carcinoma in situ, and breast carcinoma in situ, are eligible for inclusion.
2. Underwent surgery within 4 weeks prior to the start of the study treatment.
3. Known history of severe allergy to any monoclonal antibodies or excipients.
4. Previous use of PD-1 inhibitors, LAG-3 inhibitors, CTLA-4 inhibitors, or any other antibodies or drug treatments targeting T-cell co-stimulation or immune checkpoint pathways, including previous receipt of anti-tumor vaccines or other immunostimulatory anti-tumor therapies.
5. Previous exposure to VEGF (vascular endothelial growth factor) or VEGFR inhibitors or any anti-angiogenesis medications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sintilimab+Ramucirumab+SOX/XELOX	Drug: Sintilimab; Sintilimab 200mg iv.gtt d1, every 21 days; Drug: Ramucirumab; Ramucirumab 10mg/kg iv.gtt d1, every 21 days; Drug: SOX/XELOX; SOX: Oxaliplatin 130mg/m2 iv.gtt d1, every 21 days and S-1 40mg/m2 po bid d1-14, every 21 days XELOX: Oxaliplatin 130mg/m2 iv.gtt d1, every 21 days and Capecitabine 1000mg/m2 po bid d1-14, every 21 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR was defined as the proportion of participants whose tumor volume decreases to a predefined value and can maintain the minimum duration requirements, which is the sum of the rates of Complete Response (CR) and Partial Response (PR) according to RECIST 1.1 based on investigator assessment.	Up to approximately 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR)	DCR was defined as the percentage of the participants who achieve either a response (PR + CR) or Stable Disease (SD) after treatment and can maintain the minimum duration requirements according to RECIST 1.1 based on investigator assessment.	Up to approximately 12 months
Progression-free Survival (PFS)	PFS was defined as the time from the start of treatment to disease progression according to RECIST 1.1 based on investigator assessment, or death due to any cause, whichever occurs first.	Up to approximately 16 months
Overall Survival (OS)	OS was defined as the time from enrollment to death due to any cause.	Up to approximately 16 months
Incidence of adverse events and serious adverse events (AEs)	Categorized according to the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE 5.0). Descriptive statistical analysis is primarily used to list and describe the AEs that occurred during this trial.	Up to approximately 16 months

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: August 19, 2024
• First Submitted That Met QC Criteria: August 20, 2024
• First Posted (Actual): August 21, 2024

Study Record Updates

• Last Update Posted (Actual): August 28, 2024
• Last Update Submitted That Met QC Criteria: August 26, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ramucirumab
• Other Study ID Numbers: 2024-SR-654

Drug and device information, study documents

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