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

Immunotherapy Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05223088
• Other study ID #: TAOS-3B
• Status: Recruiting
• Phase: Phase 2
• Start date: October 31, 2021
• Est. completion date: April 30, 2024

Study information

• Verified date: January 2023
• Source: Fujian Cancer Hospital
• Contact: chen lu chuan, bachelor
• Phone: 13905022862
• Email: Luchuanchen[@]sina.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: April 30, 2024
• Est. primary completion date: April 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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;

Related Conditions & MeSH terms

• Immunotherapy
• Stomach Neoplasms

Intervention

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.
• Apatinib Mesylate
Participants will receive apatinib, 250mg, qd,every 3 weeks for 2-5 weeks.
• oxaliplatin
Participants will receive oxaliplatin, 130mg/m2, day 1 of every 3 weeks for 3-6 weeks.
• Tegafur
Participants will receive Tegafur, day 1-14 of every 3 weeks for 3-6 weeks.

Locations

Country	Name	City	State
China	Fujian cancer hospital	Fuzhou

Sponsors (1)

Lead Sponsor	Collaborator
Fujian Cancer Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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) ]