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

Gastric Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04997837
• Other study ID #: FDRT-2021-63-2366
• Status: Recruiting
• Phase: Phase 3
• Start date: July 21, 2021
• Est. completion date: October 21, 2027

Study information

• Verified date: August 2021
• Source: Fudan University
• Contact: Zhen Zhang, MD, PhD
• Phone: 18801735029
• Email: zhen_zhang[@]fudan.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 433
• Est. completion date: October 21, 2027
• Est. primary completion date: July 21, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Gastric Cancer

Intervention

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.
• 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.
• Capecitabine
CapeOx: 1000 mg2 (body surface area) bid orally in 14 days, followed by 7 days off.
• Tegafur-gimeracil-oteracil potassium
SOX: 40 - 60 mg bid orally in 14 days, followed by 7 days off
• 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

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	3-year OS rate	Defined as the time from randomization to death from any cause.	Up to 3 years
Secondary	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
Secondary	Percentage of participants with treatment-related acute adverse events as assessed by CTCAE v5.0		Up to 28 days from last dose
Secondary	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