Trial Title:
Capeox Regimen Combined With Sintilimab and Bevacizumab for Gastric Cancer
NCT ID:
NCT05640609
Condition:
Stomach Neoplasm
Conditions: Official terms:
Stomach Neoplasms
Bevacizumab
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Combination Product
Intervention name:
Capeox regimen combined with Sintilimab and Bevacizumab
Description:
Stage Ib：Oxaliplatin +Capecitabine Tablets +Sintilimab +Bevacizumab Stage II：Bevacizumab
(the dose determined in phase Ib clinical study)，the dosage of other drugs was the same
as before
Arm group label:
Capeox regimen combined with Sintilimab and Bevacizumab
Summary:
The median survival time of first-line chemotherapy for advanced gastric cancer is about
one year, and the treatment is still facing the bottleneck. This is a one-arm, open and
prospective phase II clinical study. Recruit patients who have been diagnosed with
advanced or metastatic adenocarcinoma of the stomach and gastroesophageal junction and
have not received systematic treatment.
Detailed description:
The median survival time of first-line chemotherapy for advanced gastric cancer is about
one year, and the treatment is still facing the bottleneck. Bevacizumab is an
anti-vascular endothelial growth factor (VEGF) targeted therapy drug. It is doubtful
whether the low dose of bevacizumab in gastric cancer patients leads to poor curative
effect. Now the treatment of advanced gastric cancer has come to the era of
immunotherapy. The chemotherapy regimen of daclizumab combined with CAPEOX has been
proved to be effective in clinical studies. No clinical study has confirmed the safety
and efficacy of CAPEOX regimen combined with sintilimab and bevacizumab.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Histological or cytological diagnosis confirmed adenocarcinoma of stomach and
gastroesophageal junction (including signet ring cell carcinoma, mucinous
adenocarcinoma, hepatoid adenocarcinoma)
2. Imaging and surgical evaluation of unresectable recurrent or metastatic patients
3. The expected survival time was more than 3 months
4. The age is between 18 and 70 years old, both male and female
5. No systematic treatment has been given to patients with advanced or metastatic
gastric and esophagogastric junction adenocarcinoma.If the patients who have
received adjuvant or neoadjuvant therapy (including chemotherapy, radiotherapy and
chemotherapy), the last treatment must be completed at least 6 months before
randomization, and there is no recurrence or disease progression at the time of
treatment.Palliative radiotherapy was allowed, but it must be completed at least 2
weeks before the first study treatment.Subjects were allowed to receive anti-tumor
traditional Chinese medicine preparations in the past, but they must be discontinued
at least 2 weeks before randomization
6. Eastern Cooperative Oncology Group(ECoG) - 1 physical status
7. At least one lesion can be evaluated according to RECIST 1.1 criteria
8. It can provide pathological tissues or fresh pathological tissues that are filed
within 6 months after the signature of informed consent for screening, and can
obtain the test results. For the slices filed within 6 months before randomization,
it should be confirmed that no systematic treatment (including adjuvant /
neoadjuvant therapy) has been received after obtaining the samples
9. The function of the main organs is normal, that is to say, it meets the following
standards:
1. Blood routine examination (no blood transfusion within 14 days before
screening)
2. Hemoglobin ≥ 90 g / L;
3. Absolute neutrophil count (ANC) ≥ 1.5×109/L;
4. Platelet count ≥ 75×109/L; Blood biochemical test (albumin was not used within
14 days before screening)
5. Albumin ≥ 28 g / L;
6. Total bilirubin ≤ 1.5×Upper limit of normal value (ULN);
7. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 3×ULN; If
there is liver metastasis, aspartate aminotransferase (AST), alanine
aminotransferase (ALT) ≤ 5×ULN
8. Creatinine ≤ 1.5×ULN;Coagulation function:
9. International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5×ULN;
10. Activated partial thromboplastin time (APTT) ≤ 1.5×ULN
10. For sections filed in the first 6 months of randomization, it should be confirmed
that no systematic treatment (including adjuvant / neoadjuvant therapy) has been
received since sample acquisition
11. Acute toxicity caused by previous anti-tumor treatment or surgery was relieved to
grade 0-1 (according to ncictcae 5.0) or to the level specified in the inclusion /
exclusion criteria
12. Female subjects of childbearing age were required to conduct a serum pregnancy test
within 3 days before the start of the study, and the results were negative, and they
were willing to use a medically recognized high-efficiency contraceptive method
(such as intrauterine device, contraceptive or condom) during the study period and
within 3 months after the last administration of the study drug;For male subjects
whose partners are women of childbearing age, they should be sterilized by surgery
or agree to use effective contraceptive methods during the study and within 3 months
after the last study administration
13. With my consent and signed the letter of understanding, I am willing and able to
follow the planned visit, research treatment, laboratory examination and other test
procedures
Exclusion Criteria:
1. HER2 + (or HER2 +) is known to be positive
2. Gastric cancer known as squamous cell carcinoma, undifferentiated or other tissue
types, or adenocarcinoma mixed with other tissue types
3. There are uncontrolled or symptomatic active central nervous system (CNS)
metastases, which can be characterized by clinical symptoms, brain edema, spinal
cord compression, cancer metastasis, malignant meningitis, leptomeningeal disease,
and / or progressive growth.Patients with CNS metastases can be enrolled in the
study if they are adequately treated and their psychiatric symptoms can return to
baseline level at least 2 weeks before randomization (except for residual signs or
symptoms related to CNS treatment).In addition, subjects were required to
discontinue corticosteroids or receive prednisone (or equivalent other
corticosteroids) at least 2 weeks before randomization, or to receive a stable or
gradually reduced dose of prednisone (or equivalent) at least 2 weeks before
randomization
4. There were hydrothorax and ascites which could not be controlled by puncture and
drainage within 14 days before the random;Pericardial effusion with clinical
symptoms or moderate or above
5. The weight of the subjects decreased by more than 20% in the first two months of
randomization
6. The following treatments or drugs were received before randomization: a) major
surgery was performed within 28 days before randomization (tissue biopsy and
peripherally inserted central catheter operation peripherally inserted central
venous catheter （PICC） for diagnosis are allowed; b) immunosuppressive drugs were
used within 7 days before randomization,Does not include nasal and inhaled
corticosteroids or physiological doses of systemic hormones (i.e. no more than 10 mg
/ D of nisone or other corticosteroids with equivalent physiologic doses);c) Live
attenuated vaccine was administered within 28 days before randomization or within 60
days after the end of drug treatment;d) Antineoplastic therapy (including
chemotherapy, radiotherapy, immunotherapy, endocrine therapy, targeted therapy,
biotherapy or tumor embolization) within 28 days before randomization
7. Any other malignant tumor was diagnosed within 3 years before entering the study,
except basal cell carcinoma of skin or squamous or superficial bladder cancer,
carcinoma in situ of cervix, intraductal carcinoma of breast and papillary thyroid
carcinoma that can be treated locally and cured.
8. There is any active, known or suspected autoimmune disease.Subjects who were in a
stable state and did not need systemic immunosuppressive therapy were allowed to be
included, such as type I diabetes mellitus, hypothyroid diabetes mellitus requiring
hormone replacement therapy only, and skin diseases without systemic treatment
(e.g., vitiligo, psoriasis and alopecia)
9. Previously received anti-PD-1 / PD-L1 antibody, anti-CTLA-4 antibody or other drugs
acting on T-cell co stimulation or examination cell co stimulation or checkpoint
pathway
10. There were significant bleeding symptoms or bleeding tendency in 3 months before
random;Gastrointestinal perforation and / or gastrointestinal fistula occurred
within 6 months before randomization;Arteriovenous thrombosis events occurred in the
first 6 months, such as cerebrovascular accident (including transient ischemic
attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and
pulmonary embolism, etc
11. Major vascular disease (e.g. aortic aneurysm requiring surgical repair or recent
peripheral artery thrombosis) within 6 months before the start of study treatment
12. Severe, unhealed or dehiscent wounds and active ulcers or untreated fractures
13. There were peripheral neuropathy > 1 grade
14. If the symptoms of ileus (ileus) at the beginning of the study (with or without
complete parenteral nutrition treatment) and symptoms of ileus were resolved at the
time of initial diagnosis or complete parenteral nutrition treatment, or if the
patient did not have the symptoms of ileus at the time of initial diagnosis /
treatment, or had not received complete parenteral nutrition treatment,Patients may
be admitted to the study
15. Interstitial lung disease, non infectious inflammation or uncontrollable systemic
diseases (such as diabetes, hypertension, pulmonary fibrosis and acute pneumonia,
etc.)
16. Known allergy to the study drug or any of its excipients, or severe allergic
reactions to other monoclonal antibodies
17. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency
syndrome (AIDS)
18. Untreated active hepatitis B was defined as HBV-DNA ≥ 500 IU / ml;Hepatitis C,
defined as HCV-RNA higher than the detection limit of the analytical method;Or
combined with hepatitis B and C co infection
19. In the first 6 months, the following conditions occurred: myocardial infarction,
severe / unstable angina pectoris, New York Heart Association （NYHA ）grade 2 or
above cardiac insufficiency, clinically significant supraventricular or ventricular
arrhythmias, and symptomatic congestive heart failure
20. Hypertension was poorly controlled by drug therapy (systolic blood pressure > 140
mmHg or diastolic blood pressure > 90 mmHg)
21. Systemic use of antibiotics for more than 7 days in 4 weeks before randomization, or
fever of unknown origin > 38.5 ° C during screening period / before first
administration (fever due to tumor can be included in the group according to the
judgment of the researcher)
22. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem
cell transplantation
23. Participated in any other drug clinical study within 4 weeks before randomization,
or no more than 5 half-life from the last study
24. A history of psychotropic substance abuse or abuse is known
25. The presence of other laboratory abnormalities with severe physical or mental
illness may increase the risk of participating in the study, or interfere with the
results of the study and patients considered unsuitable for the study
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Liu Ming
Address:
City:
Chengdu
Country:
China
Status:
Recruiting
Contact:
Last name:
Liu Ming, Ph.D/MD
Phone:
+86 18980606324
Email:
liuming629@wchscu.cn
Contact backup:
Last name:
Dai Ruihong
Phone:
18715779637
Email:
760173632@qq.com
Start date:
March 10, 2023
Completion date:
November 1, 2026
Lead sponsor:
Agency:
West China Hospital
Agency class:
Other
Source:
West China Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05640609
https://www.esmo.org/content/search?searchText=Sintilimab+plus+chemotherapy+%28chemo%29+versus+chemo+as+first-line+treatment+for+advanced+gastric+or+gastroesophageal+junction+%28G%2FGEJ%29+adenocarcino+%28ORIENT-16%29%3A+First+results+of+a+randomized%2C+double-blind%2C+phase+III+study.
