Clinical trial NCT06766578: Clinical Study of Low-dose Interval Radiotherapy Combined With Tirelizumab and SOX Chemotherapy Neoadjuvant Therapy for Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma
Official title: Clinical Study of Low-dose Interval Radiotherapy Combined With Tirelizumab and SOX Chemotherapy Neoadjuvant Therapy for Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma(STAR-02)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma
Lead sponsor: Shandong Provincial Hospital
Sponsor class: OTHER_GOV
First posted: 2025-01-09
Enrollment: 32
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: To evaluate the initial efficacy and safety of neoadjuvant low-dose interval radiotherapy combined with tirelizumab and SOX chemotherapy in locally advanced gastric/gastroesophageal junction adenocarcinoma.


Eligibility criteria: Inclusion Criteria:

* Patients voluntarily participated in the study and signed informed consent with good compliance and follow-up;
* Adenocarcinoma of the gastric/gastroesophageal junction confirmed by endoscopic pathology (tumor located in the lesser bend of the stomach other than pylorus or the gastroesophageal junction) (Note: Pathology in other hospitals must be consulted by our hospital);
* Patients with cT4N+M0 AJCC stage 8 combined with endoscopic, CT, MRI, or PETCT findings;
* Age ≥18 years, ≤75 years, male and female;
* ECOG PS score 0-1;
* Presence of measurable and/or unmeasurable lesions as defined by the efficacy evaluation criteria for solid tumors (Recist 1.1);
* Has not received any prior systemic antitumor therapy (including but not limited to systemic chemotherapy, radiotherapy, molecular targeted drug therapy, immunotherapy, biotherapy, topical therapy, or other investigational therapeutic drugs;
* The functions of vital organs meet the following requirements (no blood components and cell growth factors are allowed to be used 2 weeks before screening) : Neutrophil absolute count (ANC) ≥ 1.5×10 9/L; Platelets ≥100×10 9/L; Hemoglobin ≥9g/dL; Serum albumin ≥2.8g/dL; Total bilirubin ≤ 1.5 ×ULN, ALT, AST and/or AKP≤2.5 ×ULN; serum creatinine ≤1.5 ×ULN or creatinine clearance ≥60mL/min (calculated according to the Cockcroft-Gault formula); International standardized ratio (INR) and activated partial thrombin time (APTT) ≤1.5×ULN (INR can be screened in the expected treatment range of anticoagulants for stable doses of anticoagulants such as low molecular weight heparin or warfarin);
* Fertile female subjects shall perform a urine or serum pregnancy test within 72 hours prior to receiving the first study drug, prove negative, and be willing to use an effective method of contraception during the trial period up to 5 months after the last drug administration.Male subjects whose partner is a woman of reproductive age should use an effective method of contraception during the trial period and for 7 months after the last dose.

Exclusion criteria

* a history of surgery for gastric/esophagogastric junction tumors;
* Previous history of fistula caused by primary tumor invasion;
* Higher risk of gastrointestinal bleeding and perforation;
* Poor nutritional status, BMI less than 18.5kg/m2, or PG-SGA score ≥9;
* Major surgery or severe trauma within 4 weeks prior to first use of the study drug;
* Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage;
* has received or is currently receiving any of the following previous treatments: anti-PD-1 or anti-PD-L1 antibody therapy, chemotherapy, radiotherapy, targeted therapy;
* Received any investigational drug within 4 weeks prior to first use of the investigational drug;
* subjects requiring systemic treatment with corticosteroids (\> 10mg prednisone equivalent daily dose) or other immunosuppressants within 2 weeks prior to initial use of the study drug, except for corticosteroids for esophageal/gastric local inflammation and for the prevention of allergy and nausea and vomiting.Other special circumstances, need to communicate with the bid. In the absence of active autoimmune disease, inhaled or topical steroids and adrenocorticosteroid replacement at doses \> 10mg/ d of prednisone efficacy are permitted;
* those who have received antitumor vaccine or have received live vaccine within 4 weeks prior to the first administration of the study drug;
* have any active autoimmune disease or a history of autoimmune disease (such as interstitial pulmonary inflammation, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism); Except patients with vitiligo or recovered asthma/allergy of the same age without any intervention as adults;Patients with autoimmune mediated hypothyroidism treated with stable doses of thyroid hormone replacement and type 1 diabetes treated with stable doses of insulin could be included;
* have a history of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation or allogeneic bone marrow transplantation;
* any condition requiring systemic treatment with corticosteroids (more than 10 mg/ day of prednisone or its equivalent) or other immunosuppressant treatment within 14 days prior to treatment (except local, ocular, intraarticular, intranasal and inhaled corticosteroids with minimal systemic uptake); Prophylactic short-term (≤7 days) use of corticosteroids (e.g., to prevent contrast allergy) or for the treatment of non-autoimmune conditions (e.g., delayed hypersensitivity due to allergen exposure);
* subjects with uncontrolled cardiac clinical symptoms or disease, such as (1) NYHA II or above heart failure (2) unstable angina pecina (3) myocardial infarction within 1 year (4) clinically significant ventricular arrhythmias or ventricular arrhythmias requiring clinical intervention;
* Severe infection (CTCAE \> level 2), such as severe pneumonia, bacteremia, and infectious complications requiring hospitalization, occurred within 4 weeks prior to initial use of the study drug; Chest imaging at baseline suggested active lung inflammation and signs and symptoms of infection requiring oral or intravenous antibiotic treatment within 2 weeks prior to enrollment, except for prophylactic antibiotic use;
* a history of interstitial lung disease, non-infectious pneumonia, pulmonary fibrosis or other uncontrolled acute lung disease;
* Patients with active pulmonary tuberculosis infection found by history or CT examination, or patients with active pulmonary tuberculosis infection history within 1 year before enrollment, or patients with active pulmonary tuberculosis infection history more than 1 year ago but without formal treatment;
* Subjects with active hepatitis B (HBV DNA≥2000 IU/mL or 10 4 Copies /mL), hepatitis C (positive hepatitis C antibody, and HCV-RNA higher than the lower limit of detection method);
* Abnormal values of sodium, potassium and calcium greater than grade 1 in laboratory tests within 2 weeks before enrollment, which could not be improved after treatment;
* known allergy to macromolecular protein preparations, or to any COMPONENT of PD-1, or allergy, hypersensitivity or contraindication to oxaliplatin or capecitabine or any component used in their preparations;
* A prior diagnosis of any other malignancy, other than malignancies with a low risk of metastasis and death (5-year survival \> 90%), such as adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix;
* pregnant or lactating women; Fertile subjects unwilling or unable to use effective contraception;
* According to the investigator's judgment, subjects have other factors that may cause them to be forced to terminate the study, such as other serious diseases (including mental diseases) requiring combined treatment, other recent serious diseases (such as myocardial infarction and cerebrovascular accident) with high risk of recurrence, seriously abnormal laboratory test values, family or social factors, which may affect subjects' safety or the collection of test data.

Primary outcomes:
measure: Pathological complete response rate (pCR)
timeFrame: From date of neoadjuvant therapy until the date of postoperative pathological assessment, assessed up to 16-18 weeks.
Secondary outcomes:
measure: Major pathological response rate (MPR)
timeFrame: From date of neoadjuvant therapy until the date of postoperative pathological assessment, assessed up to 16-18 weeks.
measure: Objective response rate (ORR)
timeFrame: From date of neoadjuvant therapy until the date of surgery, assessed up to 15-17 weeks.
measure: R0 resection rate
timeFrame: From date of neoadjuvant therapy until the date of postoperative pathological assessment, assessed up to 16-18 weeks.
measure: Treatment safety
timeFrame: From date of neoadjuvant therapy until the date of 30 days post-surgery, assessed up to 19-21 weeks.
measure: Postoperative complications
timeFrame: The first 30 days following surgery.
measure: Event-free survival (EFS)
timeFrame: From date of neoadjuvant therapy until the date of the first occurrence of the above events, assessed up to 60 months.
measure: Overall survival (OS)
timeFrame: From the date of diagnosis to the date of death, assessed up to 60 months.
measure: Biomarkers
timeFrame: From the date of neoadjuvant therapy until the end of postoperative follow-up, assessed up to 60 months.
Other outcomes:
Locations:
Study officials:
References: