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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: PD-1 inhibitor; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Tegafur-gimeracil-oteracil potassium; Drug: 5-FU; Radiation: Radiotherapy; Drug: Chemotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 433
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zhen Zhang, MD, PHD; Phone Number: 18801735029; Email: zhen_zhang@fudan.edu.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Zhen Zhang, MD, PHD; Phone Number: 18801735029; Email: zhen_zhang@fudan.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PD-1 inhibitor and chemoradiotherapy; PD-1 inhibitor+CapeOX/SOX/FOLFOX for 6 weeks, followed by chemoradiotherapy; 6 weeks of PD-1 inhibitor and CapeOX/SOX/FOLFOX for 6 weeks after chemoradiotherapy, followed by PD-1 inhibitor, till 12 months after chemoradiotherapy. 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. Chemotherapy: CapeOx or SOX or FOLFOX therapy determined by investigator. Chemoradiotherapy Radiotherapy: 1.8 Gy/fx, 45-50.5Gy Chemotherapy: Capecitabine 625mg/m2 bid orally with radiotherapy; OR Tegafur-gimeracil-oteracil potassium combination drug 40-60mg bid orally with radiotherapy.	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
Active Comparator: Chemotherapy; Chemotherapy: CapeOx or SOX or FOLFOX therapy determined by investigator. CapeOX: Oxaliplatin 130 mg/m2 (body surface area) solution intravenously once-daily, followed by 20 days off. Capecitabine 1000 mg2 (body surface area) bid orally in 14 days, followed by 7 days off. SOX: Oxaliplatin 130 mg/m2 (body surface area) solution intravenously once-daily, followed by 20 days off. Tegafur-gimeracil-oteracil potassium combination drug 40 - 60 mg bid orally in 14 days, followed by 7 days off. FOLFOX: Oxaliplatin 85 mg/m2 (body surface area) solution intravenously once-daily, followed by 13 days off. 5-FU 2400-2800mg/m2/d continuous intravenous pumping for 48h, Q2W.	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year DFS rate	Defined as the time from randomization to the date of first documented progression or death from any cause.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year OS rate	Defined as the time from randomization to death from any cause.	Up to 3 years
3-year local recurrence free survival rate	Defined as the time from randomization to the date of first documented recurrence or death from any cause.	Up to 3 years
Percentage of participants with treatment-related acute adverse events as assessed by CTCAE v5.0		Up to 28 days from last dose
Quality of life as assessed by Quality of Life Scale (range 0-60)	It evaluates the quality of life from 12 aspects, including appetite, mental status, sleep quality, fatigue, etc. The higher scores mean a better quality of life.	Through study completion, up to 10 years

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Zhen Zhang, MD,PhD, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2021
• Primary Completion (Anticipated): July 21, 2027
• Study Completion (Anticipated): October 21, 2027

Study Registration Dates

• First Submitted: July 21, 2021
• First Submitted That Met QC Criteria: August 1, 2021
• First Posted (Actual): August 10, 2021

Study Record Updates

• Last Update Posted (Actual): August 10, 2021
• Last Update Submitted That Met QC Criteria: August 1, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine; Oxaliplatin; Immune Checkpoint Inhibitors; Tegafur
• Other Study ID Numbers: FDRT-2021-63-2366

Drug and device information, study documents

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