Tislelizumab Combined With Apatinib and Oxaliplatin Plus S1 as Neoadjuvant Therapy for Borrmann IV、Large Borrmann III Type and Bulky N Positive Advanced Gastric Cancer

Tislelizumab Combined With Apatinib and Oxaliplatin Plus S1 as Neoadjuvant Therapy for Borrmann IV、Large Borrmann III Type and Bulky N Positive Advanced Gastric Cancer: a Single-arm, Prospective, Multicenter Trial (TAOS-3B-Trial)

To evaluate the clinical efficacy and safety of Tislelizumab combined with apatinib mesylate, oxaliplatin plus S1.

Study Overview

• Status: Recruiting
• Conditions: Immunotherapy; Gastrict Cancer
• Intervention / Treatment: Drug: Tislelizumab; Drug: Apatinib Mesylate; Drug: oxaliplatin; Drug: Tegafur

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: chen lu chuan, bachelor; Phone Number: 86 13905022862; Email: Luchuanchen@sina.cn
• Study Contact Backup: Name: Ye zai sheng, Doctor of Medicine; Phone Number: 86 13950203076; Email: flyingengel@sina.cn

Study Locations

• China
  • Fuzhou, China
    • Recruiting
    • Fujian cancer hospital
    • Contact: chen l chuan; Phone Number: 86 13905022862; Email: Luchuanchen@sina.cn
    • Principal Investigator: chen l chuan, bachelor of medicine

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:

• Age: 18-70 years of age
• Histologically confirmed gastric adenocarcinoma was diagnosed in patients with locally advanced gastric cancer with tumor volume >5cm Borrmann III, Borrmann IV and BulkyN according to AJCC Version 8
• measurable lesions at least should be detected by CT/MRI examination in accordance with the RECIST1.1.
• ECOG（Eastern Cooperative Oncology Group）PS（Performance Status）:0-1 scores;
• No previous surgical treatment, anti-tumor chemoradiotherapy/immunotherapy was performed
• Preoperative endoscopic examination confirmed no positive peritoneal implantation metastasis and exfoliated cells
• the expected survival time is more than 6 months

• the main organ function is normal, which should meet the following criteria:

  1. HB≥ 9g/dL
  2. ANC≥1.5×109/L
  3. PLT≥100×109/L
  4. TBIL≤1.5 normal upper limit ULN ；or TBIL>ULN but BIL≤ULN
  5. ALT and AST≤2.5 ULN（ALT or AST ≤5×ULN was allowed in patients with liver metastasis）
  6. Cr≤1.5 ULN，CCR（creatinine clearance rate）≥60ml/min(Cockcroft-Gault formula)
  7. Good coagulation function, defined as international standardized ratio (INR) or prothrombin time (PT) ≤1.5 ULN
  8. Normal thyroid function, defined as thyroid stimulating hormone (TSH) within the normal range.If the baseline TSH is outside the normal range, subjects with total T3 (or FT3) and FT4 within the normal range may be enrolled;
  9. The myocardial enzyme profile is within the normal range (if the investigator comprehensively determines that the simple laboratory abnormality is not clinically significant, it is allowed to be included in the group
• For women of reproductive age, a urine or serum pregnancy test with negative results should be performed within 3 days prior to receiving the first study drug administration (day 1 of cycle 1).If a urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is requested.Women of childbearing age were defined as at least 1 year after menopause or having undergone surgical sterilization or hysterectomy;。
• If there is a risk of conception, all subjects (both men and women) are required to use a contraceptive with an annual failure rate of less than 1% throughout the treatment period up to 120 days after the last study drug (or 180 days after the last chemotherapeutic drug)
• participants is willing to participate in this study, sign the informed consent, have good compliance, cooperate with follow-up.

Exclusion Criteria:

• Diagnosis of malignant diseases other than gastric cancer within 5 years prior to first administration (excluding radical basal cell carcinoma of the skin, squamous carcinoma of the skin, and/or radical resectable carcinoma in situ);
• Significant clinical bleeding symptoms or clear bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer or vasculitis, etc. occurred within 3 months before enrollment. If fecal occult blood was positive at baseline, reexamination could be performed; if it was still positive after reexamination, gastroscopy was required
• Prior treatment: anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs or drugs that target another stimulating or co-inhibiting T-cell receptor (e.g., CTLA-4, OX-40, CD137);
• A history of immunodeficiency, including HIV testing positive.
• Is currently participating in an interventional clinical study or has been treated with another study drug or study device in the 4 weeks prior to initial dosing.
• Patients who had a history of cardiovascular and cerebrovascular diseases and were still taking thrombolytic drugs or anticoagulants orally.
• HER2 positive is known;
• Patients with previous gastrointestinal perforation, abdominal abscess or recent intestinal obstruction (within 3 months) or imaging or clinical symptoms suggesting intestinal obstruction;

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: Tislelizumab combined with apatinib and oxaliplatin plus S1; Neoadjuvant immunotherapy, PD-1, plus apatinib and oxaliplatin plus S1 will be applied to patients with Borrmann IV、large Borrmann III type and Bulky N positive advanced gastric cancer before surgery.

Drug: Tislelizumab; Participants will receive Tislelizumab, 200mg, intravenously over 30 - 60 minutes, day 1 of every 3 weeks for 3-6 weeks. Discontinuation will be considered due to toxicity, withdrawal of consent, or end of study. Every 3-week treatment period was considered to be a cycle.; Drug: Apatinib Mesylate; Participants will receive apatinib, 250mg, qd，every 3 weeks for 2-5 weeks.; Drug: oxaliplatin; Participants will receive oxaliplatin, 130mg/m2, day 1 of every 3 weeks for 3-6 weeks.; Drug: Tegafur; Participants will receive Tegafur, day 1-14 of every 3 weeks for 3-6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total/moderate tumor regression rate under pathology	Primary tumor or lymph node surgery specimen pathological examination without residual tumor cell	4 weeks after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective Response Rate Determine the tumor shrinkage rate, tumor boundary and the adhesion of tumor	At the end of Cycle 3 (each cycle is 21 days)
Overall survival (OS)	Defined from date of Signing ICF to date of first documentation of death from any cause or censored at the date of the last follow-up. Defined from date of Signing ICF to date of first documentation of death from any cause or censored at the date of the last follow-up. Defined from date of Signing ICF to date of first documentation of death from any cause or censored at the date of the last follow-up. Defined from date of Signing ICF to date of first documentation of death from any cause or censored at the date of the last follow-up.	every 3 months (up to 24 months) ]

Collaborators and Investigators

• Sponsor: Fujian Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2021
• Primary Completion (Anticipated): April 30, 2023
• Study Completion (Anticipated): April 30, 2024

Study Registration Dates

• First Submitted: January 23, 2022
• First Submitted That Met QC Criteria: January 23, 2022
• First Posted (Actual): February 3, 2022

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: January 17, 2023
• Last Verified: January 1, 2023

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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protein Kinase Inhibitors; Oxaliplatin; Apatinib; Tegafur
• Other Study ID Numbers: TAOS-3B

Drug and device information, study documents

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