Combining Sintilimab with Modified FLOT for Metastatic Gastric Cancer

PD-1 Antibody Sintilimab Combined With Modified FLOT Regimen in the Treatment of Metastatic Gastric Cancer: a Phase II Clinical Study

This study is testing a new combination of a cancer drug called Sintilimab with modified chemotherapy to see if it helps people with advanced gastric cancer feel better and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 87 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: chemotherapy, radiation, prednisone, Sintilimab, Trastuzumab
• Locations: 1 site (Shanghai, Shanghai)
• Trial ID: NCT05982301 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial evaluates the efficacy and safety of Sintilimab, a PD-1 antibody, combined with a modified FLOT chemotherapy regimen in patients with metastatic gastric cancer. The study includes two cohorts: one for patients with HER2-negative advanced gastric cancer and another for those with HER2-positive cancer, who will also receive Trastuzumab. Patients will undergo treatment cycles every two weeks, with efficacy assessed every three cycles, and will continue on maintenance therapy until disease progression or intolerable side effects occur. The trial aims to determine the optimal treatment duration and effectiveness of this combination therapy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed metastatic gastric cancer or unresectable local lesions.

Not a fit: Patients with non-adenocarcinoma gastric tumors or those who have previously received treatment for their cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with metastatic gastric cancer by enhancing the effectiveness of chemotherapy through immune checkpoint inhibition.

How similar studies have performed: Other studies combining immune checkpoint inhibitors with chemotherapy have shown promising results, indicating potential success for this approach.

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.

Where this trial is running

Shanghai, Shanghai

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai, China (Recruiting)

Study contacts

• Principal investigator: WeiJian Guo, M.D.,Ph.D. — Fudan University
• Study coordinator: WeiJian Guo, M.D.,Ph.D.

Conditions Gastric Cancer; Chemotherapy Effect; Immune Checkpoint Inhibitor