Clinical trial NCT04997837: Study of Adjuvant Chemotherapy With or Without PD-1 Inhibitors and Chemoradiotherapy in Resected pN3 Gastric (G) or GEJ Adenocarcinoma
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Gastric Cancer
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2021-08-10
Enrollment: 433
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: 3-year DFS rate
timeFrame: Up to 3 years
Secondary outcomes:
measure: 3-year OS rate
timeFrame: Up to 3 years
measure: 3-year local recurrence free survival rate
timeFrame: Up to 3 years
measure: Percentage of participants with treatment-related acute adverse events as assessed by CTCAE v5.0
timeFrame: Up to 28 days from last dose
measure: Quality of life as assessed by Quality of Life Scale (range 0-60)
timeFrame: Through study completion, up to 10 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Zhen Zhang, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: