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
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Fudan University
- Enrollment
- 433
- Locations
- 1
- Primary Endpoint
- 3-year DFS rate
Study Overview
Brief Summary
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
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.
Intervention: PD-1 inhibitor (Drug)
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.
Intervention: Oxaliplatin (Drug)
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.
Intervention: Capecitabine (Drug)
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.
Intervention: Tegafur-gimeracil-oteracil potassium (Drug)
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.
Intervention: 5-FU (Drug)
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.
Intervention: Radiotherapy (Radiation)
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.
Intervention: Chemotherapy (Drug)
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.
Intervention: Oxaliplatin (Drug)
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.
Intervention: Capecitabine (Drug)
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.
Intervention: Tegafur-gimeracil-oteracil potassium (Drug)
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.
Intervention: 5-FU (Drug)
Outcomes
Primary Outcomes
3-year DFS rate
Time Frame: Up to 3 years
Defined as the time from randomization to the date of first documented progression or death from any cause.
Secondary Outcomes
- Quality of life as assessed by Quality of Life Scale (range 0-60)(Through study completion, up to 10 years)
- 3-year OS rate(Up to 3 years)
- 3-year local recurrence free survival rate(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)
Investigators
Zhen Zhang
Professor
Fudan University