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

NCT04997837 | Recruiting Phase 3

• 1 other identifier: FDRT-2021-63-2366
• Study Type: interventional
• Target: 433
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

• Quality of life as assessed by Quality of Life Scale (range 0-60)

  Through study completion, up to 10 years

Study Arms (2)

PD-1 inhibitor and chemoradiotherapy

EXPERIMENTAL

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; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Tegafur-gimeracil-oteracil potassium; Drug: 5-FU; Radiation: Radiotherapy; Drug: Chemotherapy

Chemotherapy

ACTIVE COMPARATOR

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; Drug: Capecitabine; Drug: Tegafur-gimeracil-oteracil potassium; Drug: 5-FU

Interventions

PD-1 inhibitor 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.

PD-1 inhibitor and chemoradiotherapy

Oxaliplatin 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.

Chemotherapy; PD-1 inhibitor and chemoradiotherapy

Capecitabine DRUG

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

Chemotherapy; PD-1 inhibitor and chemoradiotherapy

Tegafur-gimeracil-oteracil potassium DRUG

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

Chemotherapy; PD-1 inhibitor and chemoradiotherapy

5-FU DRUG

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

Chemotherapy; PD-1 inhibitor and chemoradiotherapy

Radiotherapy RADIATION

1.8 Gy/Fx, 45-50.4 Gy

PD-1 inhibitor and chemoradiotherapy

Chemotherapy DRUG

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

PD-1 inhibitor and chemoradiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Related Publications (1)

• 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 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Immune Checkpoint Inhibitors; Oxaliplatin; Capecitabine; Fluorouracil; Radiotherapy; Drug Therapy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Therapeutics

Study Officials

• Zhen Zhang, MD,PhD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhen Zhang, MD, PhD

CONTACT

18801735029; zhen_zhang@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 21, 2021
• First Posted: August 10, 2021
• Study Start: July 21, 2021
• Primary Completion (Estimated): July 21, 2027
• Study Completion (Estimated): October 21, 2027
• Last Updated: August 10, 2021

Record last verified: 2021-08

Locations

CN (1)