SOX Combined With Tislelizumab and LDRT for Neoadjuvant Treatment of Locally Advanced Gastric Cancer

SOX Combined With Tislelizumab and Low-dose Radiation Therapy for Neoadjuvant Treatment of Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma: a Prospective, Multi-center, Single-arm, Phase Ib/II Clinical Trial

Neoadjuvant chemotherapy or chemoradiotherapy has become the standard neoadjuvant regimen for locally advanced G/GEJ cancer and has been recommended by a series of treatment guidelines. Although with clinical benefits of neoadjuvant chemotherapy or chemoradiotherapy, the pCR and long-term survival rates are still unsatisfactory and perioperative treatment mode for locally advanced G/GEJ cancer still needs further optimization. In this study, we will explore the efficacy and safety of chemotherapy combined with tislelizumab and LDRT in the neoadjuvant treatment for locally advanced G/GEJ cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: SOX+Tislelizumab+LDRT

Detailed Description

This is a prospective, multicenter, single-arm, phase Ib/II trial. In the phase Ib, 5 cases will be enrolled in each treatment group. In the phase II study, a total of 44 patients will be enrolled. Eligible patients will be registered and receive three cycles of SOX plus tislelizumab regimen. Simultaneously, LDRT will be planned and administered. Radical D2 gastric cancer resection will be performed 4-6 weeks after the last administration of chemotherapy plus tislelizumab. The primary endpoint of Phase Ib is to determine the optimal radiation dose for phase II study. The primary endpoint of phase II is the pathological complete response (pCR) rate. Secondary endpoints include R0 resection rate, major pathological response (MPR), objective response rate (ORR), 2-year disease-free survival (DFS) rate, 2-year overall survival (OS) rate and safety profile of the neoadjuvant regimen.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Pengfei Zhang, M.D.; Phone Number: +8617828163584; Email: fly_121988@126.com
• Study Contact Backup: Name: Ming Liu, M.D; Phone Number: +8618980606324; Email: mingliu721@aliyun.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18-75 years.
2. Histologically or cytologically confirmed diagnosis of locally advanced G/GEJ adenocarcinoma (cT3-T4a, N+, M0) as assessed by exploratory laparoscopic surgery, ultrasonography and/or CT/MRI.
3. Resectable G/GEJ cancer, as judged by experienced surgeons.
4. Eastern Cooperative Oncology Group performance score (ECOG PS) ≤1.
5. Agree to provide blood, feces, and tissue specimens.
6. The expected survival is longer than 3 months.
7. There was no previous antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy, interventional therapy, and other treatments with antitumor effects).
8. Adequate organ and hematological function.
9. Strict contraception.
10. Patients must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.

Exclusion Criteria:

1. Undergoing other drug clinical trials or having participated in any drug clinical trials one month before enrollment.
2. Other tumors that have not been treated or exist at the same time, except carcinoma in situ of the cervix, treated basal cell carcinoma or superficial bladder tumor. If the tumor was cured and no evidence of disease was found for more than 3 years, the patient can be enrolled. All other tumors must be treated at least 3 years before enrollment.
3. Allergic to oxaliplatin, S-1, tislelizumab and similar drugs, or suspected allergies.
4. With serious gastrointestinal diseases that affect the absorption of oral chemotherapy drugs, such as chronic inflammatory bowel disease.
5. History of gastric perforation within 6 months.
6. Clinical manifestations include significant arrhythmia, myocardial ischemia, severe atrioventricular block, heart failure, and severe heart valve disease; Or those with severe lung function impairment; Or those with impaired blood system, liver and kidney function who cannot tolerate radiotherapy and chemotherapy; Or severe bone marrow failure; Or those with uncontrollable infections.
7. With uncontrollable mental illness.
8. Pregnant or lactating women.
9. Unable to comply with the research program or procedures.

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: SOX+Tislelizumab+LDRT; Laparoscopic exploration is required in all patients to detect occult peritoneal metastases. All patients will start with one cycle of neoadjuvant therapy of SOX plus tislelizumab regimen: S-1: 40-60 mg Bid, d1-14, q3w; oxaliplatin: 130 mg/m2, iv drip, d1, q3w; tislelizumab: 200 mg, iv drip, d1, q3w. Then, LDRT will be performed in the target area (including the primary gastric lesion and positive/suspected positive lymph nodes). After radiotherapy, patients will receive another two cycles of SOX plus tislelizumab regimen. Radical D2 gastric cancer resection will be performed 4-6 weeks after the last administration of SOX plus tislelizumab regimen. The adjuvant therapy will start in 4-6 weeks after the surgery, and we recommend adjuvant treatment with SOX regimen for up to 5 cycles.

Drug: SOX+Tislelizumab+LDRT; All patients will start with one cycle of neoadjuvant therapy of SOX plus tislelizumab regimen: S-1: 40-60 mg Bid, d1-14, q3w; oxaliplatin: 130 mg/m2, iv drip, d1, q3w; tislelizumab: 200 mg, iv drip, d1, q3w. LDRT will be performed in the target area. After radiotherapy, patients will receive another two cycles of SOX plus tislelizumab. Radical D2 gastric cancer resection will be performed 4-6 weeks after the last administration of SOX plus tislelizumab. The adjuvant therapy will start in 4-6 weeks after the surgery, and we recommend adjuvant treatment with SOX regimen for up to 5 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR rate	defined as the absence of viable tumor cells assessed by histological evaluation criteria after neoadjuvant therapy	5 months after the last subject participating in

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection rate	defined as the rate of the complete surgical removal of any residual cancer cells in the tumor bed	5 months after the last subject participating in
MPR rate	defined as tumor residual cells ≤10% in the surgical specimen	5 months after the last subject participating in
ORR	defined as the proportion of patients with the best overall response of complete response (CR) or partial response (PR)) before surgery	5 months after the last subject participating in
2-year disease-free survival (DFS) rate	defined as the proportion of patients without disease relapse 2 years after enrolment	every 3 month postoperation up to 24 months
2-year OS rate	defined as the proportion of patients survived 2 years after enrolment	every 3 month postoperation up to 24 months

Collaborators and Investigators

• Sponsor: West China Hospital
• Investigators: Study Director: Mojin Wang, M.D., West China Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 10, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): July 30, 2026

Study Registration Dates

• First Submitted: January 31, 2024
• First Submitted That Met QC Criteria: February 18, 2024
• First Posted (Actual): February 20, 2024

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 18, 2024
• Last Verified: January 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; Antineoplastic Agents; Antineoplastic Agents, Immunological; Tislelizumab
• Other Study ID Numbers: WCH-2023-1625

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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