The Effectiveness and Safety of XELOX and Tislelizumab + PLD for Resectable Gastric Cancer (LidingStudy)

A Single-arm, Open-label, Multicenter Phase 2 Study to Evaluate XELOX + Tislelizumab in Combination With Doxorubicin Hydrochloride Liposome Injection （XELOX+PD-1+PLD）as Neoadjuvant Therapy for Resectable Gastric Cancer

This is a signle-arm, multi-center, open-lable, phase II study. The objective is to evaluate the effectiveness and safety of tislelizumab + oxaliplatin + capecitabine + PLD in the neoadjuvant treatment of resectable gastric adenocarcinoma.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: PLD; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Tislelizumab

Detailed Description

This single-arm, multicenter, open-label study plan to enroll patients with resectable stage III gastric adenocarcinoma to recieve tislelizumab + oxaliplatin + capecitabine + PLD regimen for 2 or 4 cycles, radical resection will be performed after neoadjuvant therapy. Radiological evaluation will be performed every 2 cycles to evaluate the resectability of tumor. Survival follow-up will be performed after surgery, until patient's withdrawal of informed consent, loss to follow-up or death, whichever comes first.

• Study Type: Interventional
• Enrollment (Anticipated): 38
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Qi Li, Prof.; Phone Number: 13818207333; Email: Leeqi2001@hotmail.com

Study Locations

• China
  • Shanghai, China, 200080
    • Recruiting
    • Shanghai General Hospital
    • Contact: Jingyi Zhou, Dr.; Phone Number: 15618122509; Email: jingyi_z2020@sjtu.edu.cn
    • Sub-Investigator: Haiyan Zhang, MD.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age: 18~75 years old.
2. Karnofsky Performance Status Score ≥70.
3. Histological or cytological diagnosed as gastric adenocarcinoma, HER2-, PD-1/L1+.
4. Clinical stage stage III (8th edition of the AJCC Cancer Staging Manual).
5. Physical condition and organ function allow for larger abdominal surgery.
6. Subject baseline blood routine and biochemical indicators meet the following standards: hemoglobin ≥90g/L; absolute neutrophil count (ANC) ≥1.5×10^9g/L; platelets counts (PLT) ≥100×10^9/L; alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤2.5 times the upper limit of normal (ULN); serum total bilirubin <1.5 ULN; serum creatinine <1 ULN; serum albumin ≥30g/L.

7. Heart function:

   1. Left ventricular ejection fraction (LVEF) ≥50%;
   2. 12-ECG indicates no myocardial ischemia;
   3. No history of arrhythmia requiring drug intervention before enrollment;
8. No serious concomitant diseases that make the survival time < 5 years.
9. Agree and be able to comply with the protocol during the study period.
10. Provide written informed consent before entering the study.

Exclusion Criteria:

1. Received chemotherapy, radiotherapy or immunotherapy for this gastric cancer.
2. Pregnant or breastfeeding women.
3. Women of childbearing age who had a positive pregnancy test at baseline or who did not have a pregnancy test. Menopausal women must have menopause for at least 12 months before they can become pregnant.
4. Men and women who are sexually active (possible to have children) are unwilling to use contraception during the study period.
5. Patients with mass ascites and positive abdominal free cancer cells.
6. With a history of other malignancies in the last 5 years, except for cured non-melanoma skin cancer and cervical carcinoma in situ.
7. With a history of epilepsy, central nervous system disease, or mental disorder may be judged by the investigator that their clinical severity may hinder the signing of informed consent or affect the patient's oral medication compliance.
8. Clinically severe (i.e. active) heart disease, such as symptomatic coronary heart disease, New York Heart Association (NYHA) grade II or more severe congestive heart failure, or severe arrhythmia requiring medical intervention, or the last 12 There was a history of myocardial infarction within months.
9. Patients deficiency of dihydropyrimidine dehydrogenase (DPD).
10. Peripheral nerve disease ≥ NCI CTC AE grade 2. However, the patients only with deep tendon reflex (DTR) disappears do not need to be excluded.
11. Organ transplantation requires immunosuppressive therapy.
12. Severe uncontrolled repeated infections, or other serious uncontrolled concomitant diseases.
13. Moderate or severe renal damage [creatinine clearance ≤50ml/min (calculated according to Cockroft and Gault equation), or serum creatinine> ULN].
14. Acute or chronic active hepatitis B, hepatitis C infection, hepatitis B virus (HBV) DNA>2000IU/ml or 10^4 copies/ml, hepatitis C virus (HCV) RNA>10^3 copies/ml, hepatitis B surface antigen (HbsAg) is positive at the same time as anti-HCV antibody.
15. Allergic to any research drug ingredients.
16. Participating in other trials within 4 weeks before enrollment.
17. Not suitable to participate in this trial for any reason judged by the investigator.

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: Experiment group; Pegylated Liposomal Doxorubicin + Oxaliplatin + Capecitabine + Tislelizumab; reapt every 21 days.	Drug: PLD; 20mg/m2, day 1, q3w; Other Names: Pegylated Liposomal Doxorubicin; Drug: Oxaliplatin; 130 mg/m2, day 1, q3w; Other Names: Eloxatin; Drug: Capecitabine; 1000 mg/m2, days 1-14, q3w; Other Names: Xeloda; Drug: Tislelizumab; 200 mg, day 1, q3w; Other Names: BGB-A317

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete remission rate	Completely resected tumor specimens and all sampled regional lymph nodes were detected without residual infiltration (ie ypT0 ypN0 in AJCC staging version 8.0)	4-month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Defined as the proportion of subjects whose best overall response is complete response (CR) and partial response (PR).	3-month
R0 resection rate	Defined as the proportion of patients who have achieved R0 resection. R0 surgery is defined as complete resection of the tumor without visible residual lesions either by naked eyes or under microscope.	4-month
3-year overall survival rate	Overall survival (OS) is defined as the time from the enrollment to death for any cause. The Kaplan-Meier curve of OS will be proformed to calculted the 3-year OS rate.	3-year
Progress-free survival	1) In patients who underwent radical surgery, the time from enrollment to recurrence or death; 2) in patients who did not undergo radical surgery, the time from enrollment to progression (according to RECIST 1.1) or death determined as disease progression.	3-year
3-year PFS rate	The Kaplan-Meier curve of progress-free survival will be proformed to calculted the 3-year PFS rate.	3-year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs)	AEs are evaluated according to National Cancer Institute Common Terminology Criteria v5.0.	4-month

Collaborators and Investigators

• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Investigators: Study Chair: Qi Li, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2022
• Primary Completion (Anticipated): September 30, 2023
• Study Completion (Anticipated): September 30, 2027

Study Registration Dates

• First Submitted: September 7, 2022
• First Submitted That Met QC Criteria: September 7, 2022
• First Posted (Actual): September 10, 2022

Study Record Updates

• Last Update Posted (Estimate): March 9, 2023
• Last Update Submitted That Met QC Criteria: March 7, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: resectable; PD-1; XELOX; PLD
• 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; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Capecitabine; Oxaliplatin; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: CSPC-DMS-GC-04

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