Trial Title:
Sintilimab Combined With Modified FLOT Regimen in the Treatment of Metastatic Gastric Cancer
NCT ID:
NCT05982301
Condition:
Gastric Cancer
Chemotherapy Effect
Immune Checkpoint Inhibitor
Conditions: Official terms:
Stomach Neoplasms
Paclitaxel
Oxaliplatin
Study type:
Interventional
Study phase:
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:
Drug
Intervention name:
Sintilimab, paclitaxel-albumin, oxaliplatin, 5-FU
Description:
The study has only one arm. Sintilimab 200mg d1 ivgtt+paclitaxel-albumin 125mg/m2 d1
ivgtt+oxaliplatin 85mg/m2 d1 ivgtt+5-FU 2.4g/m2 civ46h, q2w.
Arm group label:
Nab-POF
Other name:
Sintilimab+mFLOT
Summary:
This is a prospective, one-arm, single-center phase II study. The objective was to
evaluate the efficacy and safety of domestic PD-1 antibody Sintilimab combined with
modified FLOT regimen in the treatment of metastatic gastric cancer. To compare the time
of maintenance of treatment after induction of chemotherapy with sintilimab combined with
modified FLOT regimen until the reapplication of induction regimen with or without the
combination of sintilimab, and the time of secondary progression after signing informed
consent until the reapplication of induction regimen with or without the combination of
sintilimab.
Detailed description:
This study set up two cohorts, Cohort A: patients with HER2-negative advanced gastric
cancer, and planned to enroll 87 patients with initially treated advanced gastric cancer.
Thirty patients with ORR of more than 70% were enrolled in the first stage and then
further enrolled. Cohort B: advanced gastric cancer patients with HER2 positive initial
treatment, the number of enrolled is not specified. Patients with initially treated
advanced gastric cancer who meet the inclusion criteria will be enrolled in this study to
receive Sintilimab combined with mFLOT regimen. Trastuzumab was given to Cohort B. The
results were repeated every 2 weeks and evaluated every 6 weeks. The examination methods
were consistent with those at baseline. Patients without disease progression were treated
for a maximum of 6 cycles, then switched to oral capecitabine monotherapy combined with
the sintilimab until disease progression, intolerable adverse reactions, patient death,
or withdrawal of informed consent. If intolerability toxicity of albumin paclitaxel or
oxaliplatin occurs within 6 cycles, maintenance is advanced to sintilimab combined with
capecitabine monotherapy. Patients were randomly assigned to Cohort A1 and Cohort A2
after maintaining treatment progress. Cohort A1: Cohort 1 combined with mFLOT; Cohort A2:
mFLOT program Therapy. The regimen was repeated every 2 weeks and tumor efficacy was
evaluated every 3 treatment cycles. Patients without disease progression were treated for
a maximum of 6 cycles before being switched to monotherapy S-1 oral with or without
sintilimab until disease progression, intolerable adverse reactions, patient death, or
withdrawal of informed consent. The treatment should start within 1 week after the
signing of informed consent, and the time from the signing of informed consent to the
first progress should be PFS1; The time from the signing of informed consent to the
progress of induction program back to the second progress is PFS2. In this study,
peripheral blood and tissue samples of patients will be collected to analyze the
correlation between biomarkers (such as Micro-RNA, cytokine expression levels, etc.) and
efficacy and prognosis. The expected time of enrollment was 48 months, and the patients
were observed clinically until disease progression and death. (PFS2 equals PFS1 if the
induction regimen is applied again after the first disease progression and the first
efficacy evaluation is the disease progression)
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Aged ≥18 years and men or women
2. With histologically confirmed adenocarcinoma of the stomach or gastroesophageal
junction, local lesions that cannot be radically resected, or metastatic gastric
cancer
3. For treatment-naïve patients, or postoperative recurrence at least 6 months from the
last adjuvant chemotherapy
4. With Eastern Cooperative Oncology Group (ECOG) PS of 0-1
5. With a life expectancy of more than 3 months
6. Who obtain the following laboratory test data within 7 days (including the seventh
day) prior to the study screening: neutrophil count of ≥1.5 × 10^9/L, platelet count
of ≥100 × 10^9/L, hemoglobin level of ≥90 g/L, serum total bilirubin of ≤1.25 the
upper limit of normal (ULN); ALT and AST levels of ≤2.5 × ULN (≤5 × ULN for patients
with liver metastasis); serum creatinine level of ≤1.0 × ULN and creatinine
clearance of ≥50 ml/min; International Normalized ratio (INR) or prothrombin time
(PT) ≤1.5 ULN; If the subject is receiving anticoagulant therapy, PT should be
within the prescribed anticoagulant range.
7. With at least one extragastric measurable lesion (Response Evaluation Criteria in
Solid Tumors [RECIST] 1.1 criteria)
8. Patients (or their legal representative/guardian) must sign an informed consent form
indicating that they understand the purpose of the study, understand the procedures
necessary for the study, and are willing to participate in the study.
Exclusion Criteria:
1. Patients with history of other types of cancer in the last 3 years, except for cured
cervical cancer or cutaneous basal cell carcinoma.
2. Patients with symptomatic brain or leptomeningeal metastases (unless the patient has
been treated for >2 months) who has a negative imaging result within 4 weeks before
participating in the study and is stable disease at study entry.
3. Patients with clinically significant gastrointestinal obstruction, gastrointestinal
bleeding (defecate occult blood + + + and above) or perforation.
4. Patients who have received PD-1, PD-L1 or PD- L2, CD137, CTLA-4 antibody therapy, or
any other T cells stimulate or total checkpoint pathways for specific target
antibody or drugs.
5. Patients with active, or have a history and possible recurrence of autoimmune
disease of the subjects (such as: Systemic lupus erythematosus, rheumatoid
arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple
sclerosis, vasculitis, glomerulonephritis, etc.), or those at high risk (such as
those who have received an organ transplant requiring immunosuppressive therapy).
However, patients with vitiligo, psoriasis, alopecia, or Grave's disease who did not
require systemic treatment within the last 2 years, or patients with hypothyroidism
who required only thyroid hormone replacement therapy, and patients with type 1
diabetes who required only insulin replacement therapy could be enrolled.
6. Patients now with interstitial lung disease or pneumonia, pulmonary fibrosis, acute
lung diseases, radiation pneumonia.
7. Patients who received any investigational drugs or antitumor drugs within 4 weeks
prior to enrollment.
8. Patients who received immunosuppressive drugs within 4 weeks, which does not include
nasal, inhalation or other routes of topical corticosteroids or physiological doses
of systemic corticosteroids (i.e., not exceeding 10 mg/ day of prednisone or
equivalent doses of other corticosteroids), or short-term (not exceeding 7 days) use
of corticosteroids for the prevention or treatment of non-autoimmune allergic
diseases.
9. Patients who received the live attenuated vaccine within 4 weeks before the first
dose of study treatment. Note: Inactivated virus vaccines for injectable seasonal
influenza are permitted for up to 4 weeks prior to initial administration; But live
attenuated influenza vaccines are not allowed;
10. Patients who received major surgery within 4 weeks before the first dose of study
treatment(open chest, craniotomy or laparotomy) or expected during the research and
treatment need to accept major surgery not associated with this study.
11. Patients who infected with human immunodeficiency virus (HIV) disease (HIV antibody
positive), or with other acquired, congenital immunodeficiency disease, or has a
history of organ transplantation, or stem cell transplantation.
12. Patients who have chronic active hepatitis B or active active hepatitis C. Hepatitis
B virus carriers, stable after drug treatment of hepatitis B (DNA drop degree is not
higher than 200 iu/mL or copy number < 1000 copies/mL) and has cured patients with
hepatitis c (HCV RNA test negative) into the group.
13. Patients with known active tuberculosis.
14. Patients with severe infections before 4 weeks of fisrt dose of treatment, active
infection which needs oral or intravenous antibiotic therapy before 4 weeks of fisrt
dose of treatment.
15. Patients with symptomatic congestive heart failure (New York heart association grade
II - IV) or symptomatic or poorly controlled arrhythmia.
16. Patiemts with uncontrolled arterial blood pressure with specification treatment
(systolic blood pressure of greater than 160mmHg or diastolic blood pressure of
greater than 100 mmHg).
17. Patients who had any arterial thromboembolic events, including myocardial
infarction, unstable angina, cerebrovascular accident, or transient ischemic attack
within 6 months before the screening.
18. Patinets with deep vein thrombosis, pulmonary embolism, or any other serious history
of thromboembolism within 3 months (implantable venous infusion port source sex or
catheter thrombosis, or superficial venous thrombosis were not regarded as a
"severe" thromboembolism).
19. Patients who have a history of neurological or psychiatric disorders, such as
memory, epilepsy, dementia, compliance, or the peripheral nervous system disorder.
20. alcohol dependence or 1-year history of drug or drug abuse.
21. Pregnancy or lactation women; Those who are fertile but do not take adequate
contraceptive measures;
22. may lead to the following results of other acute or chronic diseases, mental illness
or abnormal laboratory values: participated in or study drug dosage associated with
an increased risk, or interfere with the interpretation of results, and according to
the researcher's judgment does not conform the patient to participate in this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Fudan University Shanghai Cancer Center
Address:
City:
Shanghai
Zip:
200032
Country:
China
Status:
Recruiting
Contact:
Last name:
Weijian Guo
Phone:
64175590
Email:
guoweijian1@hotmail.com
Start date:
February 9, 2023
Completion date:
December 2025
Lead sponsor:
Agency:
Fudan University
Agency class:
Other
Source:
Fudan University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05982301
