Trial Title:
Comparing Modified XELOX Plus Sintilimab With Standard XELOX Plus Sintilimab in First-line Treatment for HER2-negative Gastric/Gastroesophageal Junction Adenocarcinoma
NCT ID:
NCT05918094
Condition:
Gastric Cancer
Conditions: Official terms:
Adenocarcinoma
Stomach Neoplasms
Fluorouracil
Conditions: Keywords:
gastric cancer
anti-PD-1
modified chemotherapy
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Experimental dose: modified XELOX + sintilimab
Description:
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.
Arm group label:
Modified XELOX + sintilimab
Intervention type:
Drug
Intervention name:
Standard dose: standard XELOX + sintilimab
Description:
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.
Arm group label:
Standard XELOX + sintilimab
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.
Detailed description:
Subjects will be randomized in a 1:1 ratio into either the modified XELOX plus sintilimab
group or the standard XELOX plus sintilimab group. 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. 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.
The primary endpoint of this study is the progression-free survival (PFS), defined as the
time from random assignment of the subject to disease progression or death from any
cause.
All eligible patients will be randomly assigned to either the trial or control group in a
1:1 ratio based on the following stratification factors: Whether the PD-L1 CPS score >=
5; Whether the age >70 years old.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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:
1. 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.
2. 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.
3. 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
Exclusion Criteria:
- 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:
1. Have had NYHA grade 3 or 4 cardiac insufficiency within 6 months prior to
enrollment;
2. Unstable angina;
3. Have had acute myocardial infarction within 6 months prior to enrollment;
4. Have had clinically significant arrhythmias within 6 months prior to enrollment
requiring treatment or intervention.
- Infected with human immunodeficiency virus (HIV) (HIV 1/2 antibody or HIV RNA
positive).
- Known to have acute or chronic active hepatitis B (HBsAg positive and HBV DNA ≥ 1000
copies/mL) or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA
positive).
- Severe infections that are in the active phase or poorly controlled in clinical
practice. Serious infection, including but not limited to hospitalization for
complications of infection, bacteremia or severe pneumonia, within 4 weeks prior to
the first dose.
- A known history of allogeneic organ transplantation and allogeneic hematopoietic
stem cell transplantation.
- A history of allergy or known intolerance to any drug in the study regimen.
- Receiving live attenuated vaccine within 4 weeks prior to the first dose or planning
to receive during the study period.
- The toxicity of previous antitumor therapy has not returned to grade 0-1 according
to CTCAE 5.0.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-sen University Cancer Center
Address:
City:
Guangzhou
Zip:
510060
Country:
China
Status:
Recruiting
Contact:
Last name:
Ruihua Xu, MD
Phone:
+862087343795
Email:
xurh@susycc.org.cn
Contact backup:
Last name:
Feng Wang, MD, PhD
Phone:
+862087343795
Facility:
Name:
The Affliated Cancer Hospital of Guizhou Medical University
Address:
City:
Guiyang
Country:
China
Status:
Recruiting
Contact:
Last name:
Weiwei Chen
Facility:
Name:
Harbin Medical University Cancer Hospital
Address:
City:
Harbin
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Yanqiao Zhang
Contact backup:
Last name:
Dan Su
Facility:
Name:
Henan Cancer Hospital
Address:
City:
Zhengzhou
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Xiaobing Chen
Facility:
Name:
Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology
Address:
City:
Wuhan
Zip:
430030
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Xianglin Yuan
Facility:
Name:
The First Affiliated Hospital of Nanchang University
Address:
City:
Nanchang
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Xiaojun Xiang
Facility:
Name:
The Second Hospital of Dalian Medical University
Address:
City:
Dalian
Country:
China
Status:
Recruiting
Contact:
Last name:
Jinghua Sun
Contact backup:
Last name:
Lingling Xu
Facility:
Name:
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Address:
City:
Shanghai
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Jun Zhang
Facility:
Name:
West China Hospital of Sichuan University
Address:
City:
Chengdu
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Hongfeng Gou
Facility:
Name:
The Second Affiliated Hospital of Kunming Medical University
Address:
City:
Kunming
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Xuefen Lei
Start date:
April 30, 2023
Completion date:
December 2028
Lead sponsor:
Agency:
Sun Yat-sen University
Agency class:
Other
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05918094
