Clinical trial NCT06266871: SOX Combined With Tislelizumab and LDRT for Neoadjuvant Treatment of Locally Advanced Gastric Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Gastric Cancer
Lead sponsor: West China Hospital
Sponsor class: OTHER
First posted: 2024-02-20
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: pCR rate
timeFrame: 5 months after the last subject participating in
Secondary outcomes:
measure: R0 resection rate
timeFrame: 5 months after the last subject participating in
measure: MPR rate
timeFrame: 5 months after the last subject participating in
measure: ORR
timeFrame: 5 months after the last subject participating in
measure: 2-year disease-free survival (DFS) rate
timeFrame: every 3 month postoperation up to 24 months
measure: 2-year OS rate
timeFrame: every 3 month postoperation up to 24 months
Other outcomes:
Locations:
Study officials:
affiliation: West China Hospital
name: Mojin Wang, M.D.
role: STUDY_DIRECTOR
References: