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

NCT ID: NCT04997837

Last Updated: 2021-08-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 433 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-21
• Study Completion Date: 2027-10-21

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.

Conditions

Gastric Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

PD-1 inhibitor

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

CapeOx: 1000 mg2 (body surface area) bid orally in 14 days, followed by 7 days off.

Tegafur-gimeracil-oteracil potassium

Intervention Type: DRUG

SOX: 40 - 60 mg bid orally in 14 days, followed by 7 days off

5-FU

Intervention Type: DRUG

FOLFOX：2400-2800mg/m2/d continuous intravenous pumping for 48h, Q2W

Radiotherapy

Intervention Type: RADIATION

1.8 Gy/Fx, 45-50.4 Gy

Chemotherapy

Intervention Type: DRUG

Capecitabine 625mg/m2 bid orally with radiotherapy; ORegafur-gimeracil-oteracil potassium combination drug 40-60mg bid orally with radiotherapy

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.

Group Type: ACTIVE_COMPARATOR

Oxaliplatin

Intervention Type: DRUG

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

Intervention Type: DRUG

CapeOx: 1000 mg2 (body surface area) bid orally in 14 days, followed by 7 days off.

Tegafur-gimeracil-oteracil potassium

Intervention Type: DRUG

SOX: 40 - 60 mg bid orally in 14 days, followed by 7 days off

5-FU

Intervention Type: DRUG

FOLFOX：2400-2800mg/m2/d continuous intravenous pumping for 48h, Q2W

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Capecitabine

CapeOx: 1000 mg2 (body surface area) bid orally in 14 days, followed by 7 days off.

Intervention Type: DRUG

Tegafur-gimeracil-oteracil potassium

SOX: 40 - 60 mg bid orally in 14 days, followed by 7 days off

Intervention Type: DRUG

5-FU

FOLFOX：2400-2800mg/m2/d continuous intravenous pumping for 48h, Q2W

Intervention Type: DRUG

Radiotherapy

1.8 Gy/Fx, 45-50.4 Gy

Intervention Type: RADIATION

Chemotherapy

Capecitabine 625mg/m2 bid orally with radiotherapy; ORegafur-gimeracil-oteracil potassium combination drug 40-60mg bid orally with radiotherapy

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Zhen Zhang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhen Zhang, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhen Zhang, MD, PhD

Role: CONTACT

zhen_zhang@fudan.edu.cn

18801735029

Facility Contacts

Zhen Zhang, MD, PhD

Role: primary

zhen_zhang@fudan.edu.cn

18801735029

References

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.

Reference Type: DERIVED

PMID: 39545610 (View on PubMed)

Other Identifiers

FDRT-2021-63-2366

Identifier Type: -

Identifier Source: org_study_id