Neoadjuvant Chemo-hypoRT Plus PD-1 Antibody (Tislelizumab) in Resectable LA-G/GEJ

NCT05941481 | Active Not Recruiting Phase 2

• 1 other identifier: jsCANCER
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

Gastric cancer is the third leading cause of death due to cancer worldwide. Although the consensus on the surgical treatment has resulted in the improvement of curative effect during the past decades, controversies remained for the perioperative therapy of gastric cancer, especially in the selection of the optimal neoadjuvant regimens. Immunotherapy with anti-programmed cell death-1 (PD-1) antibody has demonstrated moderate efficacy in selected patients with advanced gastric adenocarcinoma. Hypofractionated radiotherapy (HypoRT) may act synergistically with immunotherapy to enhance antitumor responses. This phase II trial study want to exploit the efficacy and safety to give PD-1 antibody (Tislelizumab) with combination chemotherapy and HypoRT before surgery in treating adult patients with gastric or gastroesophageal junction adenocarcinoma.

Conditions

Gastric or Gastroesophageal Junction Adenocarcinoma

Keywords

gastric or gastroesophageal junction adenocarcinoma; neoadjuvant chemo-hypofractionated radiotherapy; PD-1 Antibody

Outcome Measures

Primary Outcomes (1)

• pathological complete remission (pCR) rate

  Pathologic complete response was defined as pT0N0M0

  From date of treatment allocation and during treatment period up to 1 year

Secondary Outcomes (7)

• Radiographic response

  From date of treatment allocation and during treatment period up to 3 months

• The R0 resection rate

  Up to 3 years

• Safety of neoadjuvant chemo-hypofractionated radiotherapy plus PD-1 antibody (Tislelizumab) Safety of neoadjuvant therapy

  1 month after the last date of treatment

• Postoperative complications

  AEs of surgery refer to complications which happen during or in 30 days after operation.

• Time to Relapse (TTR)

  Time from the date of study registration to the date of 1st documented relapse/recurrence among patients who achieve R- resection, assessed up to 3 years

Study Arms (1)

neoadjuvant chemo-hypofractionated radiotherapy plus PD-1 antibody

EXPERIMENTAL

1. Immunotherapy combined with chemotherapy (2 cycles): Intravenous tislelizumab (200mg, d1, q21d) in combination with XELOX regimen (capecitabine 1000 mg/m2 bid\*14d + oxaliplatin 130mg/m2, d1, q21d); 2. Concurrent radiotherapy: Within one week after the first initiation of chemo-immunotherapy, concurrent hypofractionated radiotherapy will be started: intensity modulated radiotherapy was given for tumors, total dose:30Gy/12f, 2.5Gy/f. 3. D2 resection will be received three to five weeks after the completion of neoadjuvant therapy.

Combination Product: neoadjuvant chemo-hypofractionated radiotherapy plus PD-1 antibody (Tislelizumab)

Interventions

neoadjuvant chemo-hypofractionated radiotherapy plus PD-1 antibody (Tislelizumab) COMBINATION_PRODUCT

1. Immunotherapy combined with chemotherapy (2 cycles): Intravenous tislelizumab (200mg, d1, q21d) in combination with XELOX regimen (capecitabine 1000 mg/m2 bid\*14d + oxaliplatin 130mg/m2, d1, q21d); 2. Concurrent radiotherapy: Within one week after the first initiation of chemo-immunotherapy, concurrent hypofractionated radiotherapy will be started: intensity modulated radiotherapy was given for tumors, total dose:30Gy/12f, 2.5Gy/f.

neoadjuvant chemo-hypofractionated radiotherapy plus PD-1 antibody

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma involving the gastroesophageal junction or gastric cardia.
• Having an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 7 days before enrollment.
• Being histologically diagnosed with adenocarcinoma.
• Having tumor lesions at stomach or gastroesophageal junction (Siewert type II or III);
• Clinically diagnosed stage T1-2N+M0/T3-T4aNanyM0 according to ultrasound endoscopy or enhanced CT/MRI scan.
• At least one evaluable lesion in abdominal CT/MRI according to RESIST 1.1 is required.
• Surgical consultation at enrolling site to confirm that patient will be able to undergo curative resection after completion of neoadjuvant therapy =\< 56 days prior to registration.
• Physical condition and adequate organ function to ensure the success of abdominal surgery.
• Adequate hematological function: Neutrophil count ≥ 1.5 × 109/L, Platelets ≥ 100 × 109/L and Hemoglobin ≥90g/L.
• Adequate liver function: Total bilirubin ≤ 1.5 × upper limit of normal (ULN); AST (SGOT) and ALT (SGPT) \< 2.5 × ULN in the absence of liver metastases, or \< 5 × ULN in case of liver metastases. ALP ≤ 2.5 × upper limit of normal (ULN); ALB ≥30g/L.
• Adequate renal function: Serum creatinine ≤ 1.5 x ULN, and creatinine clearance ≥ 60 ml/min.
• Adequate coagulation function: INR/PT≤ 1.5 x ULN, aPTT≤ 1.5 x ULN.
• No serious concomitant disease that will threaten the survival of patients to less than 5 years.
• Male or female. Age ≥ 18 years and ≤80 years.
• Written (signed) informed consent.

You may not qualify if:

• Patients with distant metastasis or unresectable primary lesion.
• Received prior treatment or receiving current treatment for this malignancy.
• Patients who have digestive tract bleeding in 2 weeks before recruitment or with high risk of bleeding.
• Perforation / fistula of GI tract in 6 months before recruitment.
• Patients with upper GI tract obstruction or functional abnormality or malabsorption syndrome, which can affect absorption of apecitabine.
• Patients with active autoimmune disease or history of refractory autoimmune disease.
• Patients with active malignant tumor in recent 2 years, except the tumor studied in this research or cured locally tumor like resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical or breast carcinoma in situ.
• Uncontrollable pleural effusion, pericardial effusion, or ascites in 2 weeks before recruitment.
• Pulmonary disease history: interstitial pulmonary disease, non-infective pneumonitis, pulmonary fibrosis, acute pulmonary disease.
• Uncontrollable systemic diseases, including diabetes, hypertension, etc.
• Severe chronic or active infections in need of systemic antibacterial, antifungal, or antiviral treatment, including TB or HIV, etc.
• Patients with untreated chronic hepatitis B or HBV DNA over 500 IU/ml or positive HCV RNA.
• Patients with any cardiovascular risk factors below:
• cardiac chest pain occurring in 28 days before recruitment, defined as moderate pain that limits daily activity.
• pulmonary embolism with symptoms occurring in 28 days before recruitment.

Sponsors & Collaborators

• Jiangsu Cancer Institute & Hospital: lead

Study Sites (1)

Jiangsu Cancer Hospital

Nanjing, Jiangsu, 210009, China

Location

MeSH Terms

Interventions

tislelizumab

Study Officials

• Cheng Chen, doctor

  Jiangsu Cancer Institute & Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D

Study Record Dates

• First Submitted: July 4, 2023
• First Posted: July 12, 2023
• Study Start: June 10, 2023
• Primary Completion: May 10, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: May 28, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)