Comparing Modified XELOX Plus Sintilimab With Standard XELOX Plus Sintilimab in First-line Treatment for HER2-negative Gastric/Gastroesophageal Junction Adenocarcinoma

NCT05918094 | Recruiting Phase 3

• 1 other identifier: mXELOX SYSUCC
• Study Type: interventional
• Target: 540
• Locations: 1 country
• Sites: 10

Brief Summary

This is a randomized, controlled, multicenter phase Ⅲ study to evaluate the therapeutic efficacy of modified XELOX plus sintilimab versus standard XELOX plus sintilimab in subjects with advanced HER2-negative gastric or gastroesophageal adenocarcinoma in the first-line treatment. The primary outcome is the progression-free survival (PFS), with a planned enrollment of 540 subjects.

Conditions

Gastric Cancer

Keywords

gastric cancer; anti-PD-1; modified chemotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Time from randomization to disease progression or death from any cause

  an average of 4 years

Secondary Outcomes (6)

• Objective Response Rates (ORR)

  an average of 4 years

• Overall Survival (OS)

  an average of 4 years

• Disease Control Rate (DCR)

  an average of 4 years

• Duration of Response (DOR)

  an average of 4 years

• Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)

  an average of 4 years

Study Arms (2)

Modified XELOX + sintilimab

EXPERIMENTAL

The treatment option for the modified XELOX group (study group) is 200 mg of sintilimab IV Drip Q3W, 600 mg/m2 of capecitabine PO BID for day 1-14, and oxaliplatin 78 mg/m2 IV Drip Q3W. After 6 cycles of treatment, patients could choose capecitabine + sintilimab maintenance with a maximum treatment duration of 2 years.

Drug: Experimental dose: modified XELOX + sintilimab

Standard XELOX + sintilimab

ACTIVE COMPARATOR

The treatment option for the standard XELOX group (control group) is 200 mg of sintilimab IV Drip Q3W, 1000 mg/m2 of capecitabine PO BID for day 1-14, and oxaliplatin 130 mg/m2 IV Drip Q3W. After 6 cycles of treatment, patients could choose capecitabine + sintilimab maintenance with a maximum treatment duration of 2 years.

Drug: Standard dose: standard XELOX + sintilimab

Interventions

Experimental dose: modified XELOX + sintilimab DRUG

The treatment option for the modified XELOX group (study group) is 200 mg of sintilimab IV Drip Q3W, 600 mg/m2 of capecitabine PO BID for day 1-14, and oxaliplatin 78 mg/m2 IV Drip Q3W.

Modified XELOX + sintilimab

Standard dose: standard XELOX + sintilimab DRUG

The treatment option for the standard XELOX group (control group) is 200 mg of sintilimab IV Drip Q3W, 1000 mg/m2 of capecitabine PO BID for day 1-14, and oxaliplatin 130 mg/m2 IV Drip Q3W.

Standard XELOX + sintilimab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a good understanding of the study, are willing to follow the requirements of the study, and voluntarily sign the informed consent form.
• Aged ≥ 18 years old and ≤ 75 years old.
• Locally advanced unresectable or metastatic gastric or gastroesophageal adenocarcinoma confirmed by pathological histology or cytology.
• No previous systemic therapy. Note: Patients who have previously received neoadjuvant or adjuvant therapy may be enrolled if they have ended treatment without recurrence or disease progression for at least 6 months.
• Agree to provide a previously stored tumor tissue sample or a biopsy to collect tumor tissue.
• ECOG PS score is in the range of 0\~1.
• Expected survival time ≥ 3 months.
• Subjects having adequate organ and bone marrow functions with laboratory test values within 7 days prior to enrollment meeting the following requirements (no blood components, cell growth factors, albumin, and other corrective therapy drugs are allowed to be given within the first 14 days of obtaining laboratory tests), as follows:
• Blood routine: absolute neutrophil count (ANC) ≥ 1.5×10\^9/L; platelet count (PLT) ≥ 75×10\^9/L; hemoglobin level (HGB) ≥ 7.5 g/dL.
• Liver function: serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN in subjects without liver metastases, and ALT and AST ≤ 5.0 × ULN in subjects with liver metastases; serum albumin ≥ 25 g/L.
• Renal function: serum creatinine (Cr) ≤ 1.5 x ULN, or creatinine clearance\>50 mL/min.
• Female subjects of childbearing age or male subjects whose sexual partners are at childbearing age are required to take effective contraception measures throughout the treatment period and for 6 months after the treatment

You may not qualify if:

• Prior exposure to any immune checkpoint inhibitors (anti-PD-1 antibody, anti-PD-L1 antibody, CTLA-4 antibody).
• Receiving antitumor cytotoxic drugs, biological drugs (such as monoclonal antibodies), immunotherapy (such as interleukin 2 or interferon), or other investigational treatments within 4 weeks prior to enrollment.
• Receiving radiotherapy within 4 weeks prior to the first dose.
• Have undergone major surgical surgery within 4 weeks prior to enrollment or have not fully recovered from previous surgery.
• Known presence of symptomatic CNS metastases and/or carcinomatous meningitis. Subjects with prior treatment for brain metastases may participate in the study provided that the brain metastases have remained stable for at least 4 weeks prior to the first dose of study treatment; and that neurological symptoms have recovered to ≤ grade 1 by NCI CTCAE version 5.0.
• A history of other primary malignancies, except: malignancies in complete response for at least 2 years prior to enrollment and requiring no other treatment during the study period; adequately treated non-melanoma skin cancer or malignant freckled nevus with no evidence of disease recurrence; adequately treated carcinoma in situ with no evidence of disease recurrence.
• Active autoimmune disease requiring systemic therapy (e.g., use of disease-relieving drugs, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Alternative therapies (e.g., thyroxine, insulin, or physiologic corticosteroids for adrenal or pituitary insufficiency) are allowed. A known history of primary immunodeficiency. For patients with only positive autoimmune antibodies, the presence of autoimmune diseases should be confirmed at the discretion of the investigator.
• A history of gastrointestinal perforation and/or fistula in the previous 6 months.
• Presence of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition).
• Confirmed as HER2-positive (i.e., IHC 3+ or IHC 2+ with ISH+) gastric or gastroesophageal adenocarcinoma.
• Have heart symptoms or diseases that are not well controlled, such as:
• Have had NYHA grade 3 or 4 cardiac insufficiency within 6 months prior to enrollment;
• Unstable angina;
• Have had acute myocardial infarction within 6 months prior to enrollment;
• Have had clinically significant arrhythmias within 6 months prior to enrollment requiring treatment or intervention.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (10)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

The Affliated Cancer Hospital of Guizhou Medical University

Guiyang, Guizhou, China

RECRUITING

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

NOT YET RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, China

NOT YET RECRUITING

Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, 430030, China

NOT YET RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

NOT YET RECRUITING

The Second Hospital of Dalian Medical University

Dalian, Liaoning, China

RECRUITING

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, China

NOT YET RECRUITING

West China Hospital of Sichuan University

Chengdu, Sichuan, China

NOT YET RECRUITING

The Second Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, China

NOT YET RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

sintilimab

Condition Hierarchy (Ancestors)

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

Study Officials

• Ruihua Xu, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ruihua Xu, MD

CONTACT

+86 20 87343795; xurh@sysucc.org.cn

Feng Wang, MD, PhD

CONTACT

+86 20 87343795; wangfeng@sysucc.org.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, President

Model Details: 540 subjects will be randomized in a 1:1 ratio into either the modified XELOX plus sintilimab group or the standard XELOX plus sintilimab group.

Study Record Dates

• First Submitted: June 15, 2023
• First Posted: June 26, 2023
• Study Start: April 30, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: January 26, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (10)