Study of Adjuvant Chemotherapy With or Without PD-1 Inhibitors and Chemoradiotherapy in Resected pN3 Gastric (G) or GEJ Adenocarcinoma

Official title

A Multicenter, Randomized, Controlled Phase III Study of Chemotherapy With or Without PD-1 Inhibitors and Chemoradiotherapy as Adjuvant Regimen for D2/R0 Resected pN3 Gastric (G) or Gastroesophageal Junction (GEJ) Adenocarcinoma

Overview

The purpose of the study is to evaluate the efficacy and safety of postoperative adjuvant chemotherapy with PD-1 inhibitors and chemoradiotherapy, in comparison with adjuvant chemotherapy only, in D2/R0 resected pN3 gastric or gastroesophageal junction adenocarcinoma. PD-1+CRT cohort: A total of 216 patients will receive 6 weeks of PD-1 inhibitors and chemotherapy, then receive concurrent chemoradiotherapy, followed by 6 weeks of PD-1 inhibitors and chemotherapy, finally receive maintenance treatment of PD-1 inhibitors until (maximum 1year after radiotherapy). CT cohort: A total of 217 patients will receive 6 months of chemotherapy. The disease-free survival(DFS), overall survival(OS) and adverse effects will be analyzed.

Interventions

• Drug PD-1 inhibitor
  Nivolumab/Toripalimab 240mg solution intravenously once daily, Q2W. OR Nivolumab/Toripalimab 360mg solution intravenously once daily, Q3W; OR Pembrolizumab/Tilelizumab/Sintilimab/Carrelizumab, 200mg solution intravenously once daily, Q3W.
• Drug Oxaliplatin
  CapeOx: 130 mg/m2 (body surface area) solution intravenously once-daily, followed by 20 days off. FOLFOX: 85 mg/m2 (body surface area) solution intravenously once-daily, followed by 13 days off.
• Drug Capecitabine
  CapeOx: 1000 mg2 (body surface area) bid orally in 14 days, followed by 7 days off.
• Drug Tegafur-gimeracil-oteracil potassium
  SOX: 40 - 60 mg bid orally in 14 days, followed by 7 days off
• Drug 5-FU
  FOLFOX：2400-2800mg/m2/d continuous intravenous pumping for 48h, Q2W
• Radiation Radiotherapy
  1.8 Gy/Fx, 45-50.4 Gy
• Drug Chemotherapy
  Capecitabine 625mg/m2 bid orally with radiotherapy; ORegafur-gimeracil-oteracil potassium combination drug 40-60mg bid orally with radiotherapy

Primary outcome measures

• 3-year DFS rate [Time frame: Up to 3 years]

Secondary outcome measures (4)

• 3-year OS rate [Time frame: Up to 3 years]
• 3-year local recurrence free survival rate [Time frame: Up to 3 years]
• Percentage of participants with treatment-related acute adverse events as assessed by CTCAE v5.0 [Time frame: Up to 28 days from last dose]
• Quality of life as assessed by Quality of Life Scale (range 0-60) [Time frame: Through study completion, up to 10 years]

Eligibility criteria

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1
• Patients with expected survival time more than 6 months
• Patients after standard D2/R0 resection
• Postoperative histologically confirmed adenocarcinoma of the stomach or GEJ
• Positive lymph nodes more than 7, stage pN3
• Patients without distant metastasis (M0) or M1 with abdominal exfoliated cell detection positive (CY1P0)
• Patients' physical condition and visceral function allows following adjuvant therapy, including chemotherapy, chemoradiotherapy and PD-1 inhibitor therapy.
• Patients' blood routine and biochemical indicators should meet the following standard: Hb≥90g/L, ANC≥1.5\*10\^9/L, PLT≥100\*10\^9/L, ALT \& AST≤2.5 U/L, TB ≤ 1.5 UNL, serum creatinine<1 UNL.
• Patients who are willing to obey regimens during the study.
• Written informed consent is acquired before random entry, and patients should know that he/she has the right to quit, and following treatment won't be affected.
• Patients are willing to provide samples of blood and tissue.

Exclusion criteria

• Patients with gross peritoneal metastasis (CY1P0 excluded) or distant metastasis.
• Patients who has received any anti-tumor therapy before surgery.
• Patients who had received radiotherapy for abdominal organs including stomach, liver, kidney, etc.
• Patients who had active systematic autoimmune diseases which need systematic treatment within 2 years before first medication in the study, substitutive therapy (such as thyroxine, insulin, etc) excluded.
• Patients diagnosed with immunodeficiency, or was receiving systematic glucocorticoid treatment or other immunosuppressive therapy within 7 days before medication, physiological dose of glucocorticoid is allowed (≤10 mg/d prednison or equivalent medication)
• Patients who have known severe allergic reaction (≥level 3) to anti-PD-1 monoclonal antibody, 5-FU, Oxaliplatin or any auxiliary material.
• Patient diagnosed with other malignant tumor in the past 5 years, excluding radical basal cell carcinoma of the skin and/or radical resected carcinoma in situ.
• Patient with severe vital organ failure.
• Pregnant or lactation period
• Patient with known mental illness or drug abuse that may influence compliance.
• Patient with known HIV infection, or active tuberculosis.
• Untreated active hepatitis B
• Patient with active HCV infection
• Uncontrolled complications
• Other situations that might disturb study results and compliance.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Fudan University Shanghai Cancer Center — Shanghai

Publications

• Yang W, Zhou M, Li G, Zhou C, Wang L, Xia F, Zhang H, Shen L, Wang Y, Wan J, Wang Y, Zhao G, Zhang Z. Adjuvant chemoradiotherapy plus PD-1 inhibitor for pN3 gastric cancer: a randomized, multicenter, Phase III trial. Future Oncol. 2024 Dec;20(40):3389-3396. doi: 10.1080/14796694.2024.2421156. Epub 2024 Nov 15. PMID 39545610

Identifiers

NCT: NCT04997837 · FDRT-2021-63-2366

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗