Neoadjuvant Apatinib Combined With Sintilimab and Perioperative SOX Versus Neoadjuvant Sintilimab Combined With Perioperative SOX for Intestinal Type of Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma

NCT06925243 | Recruiting Phase 3 DMC

• 1 other identifier: LanzhouU2H-2025A-120
• Study Type: interventional
• Target: 682
• Locations: 1 country
• Sites: 4

Brief Summary

This study aims to compare the efficacy and safety of neoadjuvant apatinib combined with sintilimab and perioperative SOX chemotherapy versus neoadjuvant sintilimab combined with perioperative SOX chemotherapy in locally advanced intestinal-type gastric cancer/gastroesophageal junction adenocarcinoma. The primary questions include:

1. 1.Whether the complete remission rate (pCR) of the apatinib combined with sintilimab and SOX regimen is higher than that of the sintilimab combined with SOX regimen.
2. 2.The safety of the apatinib combined with sintilimab and SOX regimen.
3. 3.Experimental Group: Participants will receive an intravenous injection of sintilimab (200 mg) combined with the SOX regimen (oxaliplatin 130 mg/m² and S-1, with the initial dose determined based on body surface area). Additionally, apatinib (250 mg) will be administered orally once daily during the first three neoadjuvant cycles.
4. 4.Control Group: Participants will receive treatment with the sintilimab combined with the SOX regimen.

Conditions

Gastric Cancer (Including Stomach and Gastroesophageal Junction [GEJ]); Neoadjuvant Therapy; Adjuvant Chemotherapy; pCR Rate; MPR; ORR,OS,PFS

Keywords

apatinib; sintilimab; SOX; Neoadjuvant therapy; gastric cancer; intestinal type

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR) rate

  Pathological Complete Response rate (pCR) refers to the proportion of cases in which no active cancer cells are detected in the surgically resected tumor tissue after neoadjuvant therapy, as assessed using the Becker TRG grading system.

  Enrollment to surgical treatment takes about 4 months.

Secondary Outcomes (12)

• Major pathological response (MPR) rate

  Enrollment to surgical treatment takes about 4 months.

• Objective response rate (ORR)

  From enrollment to preoperative imaging assessment, it takes approximately 4 months.

• 3-year survival rate (3-year OS rate)

  From the point of enrollment to the end of the 3-year follow-up period.

• Adverse Event

  From enrollment to the completion or discontinuation of treatment, an estimated duration of eight months is expected.

• Disease control rate (DCR)

  From enrollment to preoperative imaging assessment, it takes approximately 4 months.

Study Arms (2)

Neoadjuvant apatinib combined with sintilimab and perioperative SOX group

EXPERIMENTAL

Participants will receive an intravenous injection of sintilimab (200 mg) combined with the SOX regimen (oxaliplatin 130 mg/m² and S-1, with the initial dose determined based on body surface area). Additionally, apatinib (250 mg) will be administered orally once daily during the first three neoadjuvant cycles. This treatment will be administered for three to four cycles prior to surgery, followed by radical surgery, including D2 or D2+ lymph node dissection. Within 3 to 6 weeks post-surgery, patients will begin adjuvant SOX chemotherapy. Postoperative patients will receive four cycles of adjuvant SOX chemotherapy, administered every three weeks.

Drug: Neoadjuvant apatinib combined with sintilimab and perioperative SOX

Neoadjuvant sintilimab combined with perioperative SOX group

ACTIVE COMPARATOR

Participants will receive an intravenous injection of sintilimab (200 mg) combined with the SOX regimen (oxaliplatin 130 mg/m² and S-1, with the initial dose determined based on body surface area). This treatment will be administered for three to four cycles prior to surgery, followed by radical surgery, including D2 or D2+ lymph node dissection. Within 3 to 6 weeks post-surgery, patients will begin adjuvant SOX chemotherapy. Postoperative patients will receive four cycles of adjuvant SOX chemotherapy, administered every three weeks.

Drug: Neoadjuvant sintilimab combined with perioperative SOX

Interventions

Neoadjuvant apatinib combined with sintilimab and perioperative SOX DRUG

Sintilimab: 200mg, iv, day 1 Oxaliplatin: 130 mg/m², iv, day 1 S-1: 40-60 mg/m², po, day 1-14 (BSA \< 1.25 m², 40 mg bid, 1.25 m² ≤ BSA \< 1.5 m², 50 mg bid, BSA ≥ 1.5 m², 60 mg bid) Apatinib: 250mg, po, day1-21, for 3 cycles preoperatively

Neoadjuvant apatinib combined with sintilimab and perioperative SOX group

Neoadjuvant sintilimab combined with perioperative SOX DRUG

Sintilimab: 200mg, iv, day 1 Oxaliplatin: 130 mg/m², iv, day 1 S-1: 40-60 mg/m², po, day 1-14 (BSA \< 1.25 m², 40 mg bid, 1.25 m² ≤ BSA \< 1.5 m², 50 mg bid, BSA ≥ 1.5 m², 60 mg bid)

Neoadjuvant sintilimab combined with perioperative SOX group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type of Participant and Disease Characteristics
• Patients must have a pathologically confirmed diagnosis of HER-2 negative tumor and intestinal type gastric or gastroesophageal junction adenocarcinoma according to Lauren's histological subtypes.
• Patients must have previously untreated locally advanced gastric or gastroesophageal junction adenocarcinoma (stage cT2 to cT4), with lymph nodes ranging from N0 to N3 and no evidence of metastatic disease (M0).
• Patients with Siewert type 2 or 3 tumors are eligible. Enrollment of participants with Siewert type 1 tumors will be limited to those for whom the planned treatment is perioperative chemotherapy and resection.
• Demographics
• Male or female subjects must be between the ages of ≥ 18 and ≤ 75 years at the time of signing the informed consent.
• Expected Survival: The expected survival time must be ≥ 12 weeks.
• Performance Status: Subjects must have an ECOG performance status of 0 or 1.
• Male Contraception: Non-sterilized male subjects who are sexually active with a female partner of childbearing potential must use an effective method of contraception from Day 1 through 120 days after receipt of the final dose of the investigational product. It is strongly recommended for the female partner of a male subject to also use an effective method of contraception throughout this period.
• Female subjects of childbearing potential must be willing to use adequate contraception methods throughout the study and for 120 days after the last dose of the study drug. The decision to discontinue contraception after this time point should be discussed with the attending physician. Periodic abstinence, contraceptive rhythm methods, and withdrawal are not acceptable forms of contraception.
• Females of childbearing potential are defined as those who are not surgically sterile (e.g., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause).
• Highly effective contraception methods, resulting in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, are required. Acceptable methods include a combination of a hormonal method (e.g., contraceptive pill) and a barrier method (e.g., male condom plus spermicide) to prevent pregnancy.
• Barrier methods include male condom plus spermicide, copper T intrauterine device, and levonorgestrel-releasing intrauterine system.
• ii.Hormonal methods include implants, hormone injection, combined pill, minipill, and patch.
• If a female subject becomes pregnant or suspects pregnancy during her participation in the study or her partner's participation, she must promptly inform her treating physician.

You may not qualify if:

• Medical Conditions
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has a known additional malignancy that is progressing or has required active treatment within the past 5 years (except for cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, or carcinoma in situ that has undergone potentially curative therapy).
• Has an active infection requiring systemic therapy.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years. (NOTE: Subjects with vitiligo, alopecia, Grave's disease, Type I diabetes mellitus, hypothyroidism (e.g., following Hashimoto's syndrome) only requiring hormone replacement on a stable dose (without adjustment in the first 4 weeks of study treatment), psoriasis or eczema not requiring systemic treatment (within the past 2 years), or conditions not expected to recur in the absence of an external trigger are not excluded.)
• Has any complications requiring systemic treatment with corticosteroids such as prednisone (\> 10mg/day) or other immunosuppressive medications within 14 days prior to the first administration. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed.
• History of primary immunodeficiency.
• Has received a live vaccine or other immune-activating anti-tumor drugs (such as interferon, interleukin, thymosin, or immunotherapy) within 30 days prior to the first dose of study treatment.
• Has a known history of active tuberculosis.
• Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
• Has a known severe allergy or hypersensitivity to sintilimab or apatinib or any of the study chemotherapy agents and/or to any of their excipients.
• Presence of any of the following cardiovascular and cerebrovascular diseases or cardiovascular and cerebrovascular risk factors:
• Grade II or higher myocardial ischemia or myocardial infarction, poorly controlled arrhythmia (including QTc interval ≥ 480 ms), grade III or IV cardiac insufficiency, or left ventricular ejection fraction (LVEF) \< 50.0% as determined by ultrasonic cardiography.
• Cerebrovascular accident, transient ischemic attack, or other arteriovenous thrombotic, embolic, or ischemic events.
• Prior/Concomitant Therapy

Sponsors & Collaborators

• Zuoyi Jiao: lead

Study Sites (4)

First Hospital of Lanzhou University

Lanzhou, Gansu, 730000, China

RECRUITING

Gansu Provincial Hospital

Lanzhou, Gansu, 730000, China

RECRUITING

Lanzhou University Second Hospital

Lanzhou, Gansu, 730000, China

RECRUITING

The Gastrointestinal Surgery Department, Sun Yat-sen University Cancer Center Gansu Hospital

Lanzhou, Gansu, 730000, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

sintilimab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Central Study Contacts

Bo Long

CONTACT

+86 130 0878 1208; longbo_107@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Professor

Study Record Dates

• First Submitted: March 30, 2025
• First Posted: April 13, 2025
• Study Start: April 15, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2030
• Last Updated: April 22, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)