Sintilimab Plus FOLFIRI as Second-line Therapy for Patients With HER2-negative Advanced Gastric Cancer

Official title

Sintilimab Plus FOLFIRI as Second-line Therapy for Patients With HER2-negative Advanced Gastric Cancer: a Prospective Single-arm Phase II Study

Overview

The combination of immune checkpoint inhibitors and platinum containing dual drugs are more used as a first-line therapeutic approach for patients diagnosed with advanced gastric cancer for its superior efficacy. However, there are no standard recommendations for subsequent treatment after progression on first-line therapy. Here, the investigators conduct this open-label, monocenter, single arm phase II study to evaluate whether sintilimab in combination with irinotecan, leucovorin folinate and fluorouracil can be the second-line therapy for patients diagnosed with HER2-negative unresectable or metastatic gastric cancer progression on first-line therapy. Patients participated in this study will receive sintilimab 3mg/kg for patients with body weight\<60kg or 200mg for patients with body weight ≥ 60kg, plus irinotecan 180mg/m2 intravenous infusion, leucovorin folinate 400mg/m2 intravenous infusion and fluorouracil 400mg/m2 intravenous injection followed by 2400mg/m2 intravenous infusion for 48 hours, repeated every two weeks. The primary endpoint is 5-month progression-free survival (PFS) rate. The investigators estimated that 27 patients were necessary. Secondary endpoints include overall survival, progression-free survival, objective response rate, disease control rate and safety for unresectable or metastatic gastric cancer. Exploratory endpoint is to detect the baseline ctDNA level of patients before initial treatment.

Interventions

• Drug Sintilimab+irinotecan+leucovorin folinate+fluorouracil
  sintilimab 3mg/kg for patients with body weight\<60kg or 200mg for patients with body weight ≥ 60kg, plus irinotecan 180mg/m2 intravenous infusion, leucovorin folinate 400mg/m2 intravenous infusion and fluorouracil 400mg/m2 intravenous injection followed by 2400mg/m2 intravenous infusion for 48 hours, repeated every two weeks.

Primary outcome measures

• 5-month progression-free survival (PFS) rate [Time frame: Undergo imaging examination to evaluate efficacy every 8 weeks ±7 days]

Secondary outcome measures (5)

• Overall survival [Time frame: From the date of enrollment to the date of death from any cause, assessed up to 60 months.]
• Progression free survival [Time frame: From the date of enrollment to the first documentation of disease progression or all-cause death, whichever occurs first, assessed up to 60 months.]
• Objective response rate [Time frame: Undergo imaging examination to evaluate efficacy every 8 weeks ±7 days]
• Disease control rate [Time frame: Undergo imaging examination to evaluate efficacy every 8 weeks ±7 days]
• Adverse Events [Time frame: from the date of the first medicine to 28±7 days after the last medicine]

Eligibility criteria

Inclusion criteria

• Metastatic or locally advanced, unresectable HER2-negative gastric adenocarcinoma confirmed by histology or cytology
• Progression or toxicity intolerance of first-line treatment
• Patients aged ≥ 18 years
• ECOG score 0-2
• Estimated life expectancy of at least 12 weeks
• Adequate organ and bone marrow function, as follows: Hemoglobin ≥8g/dl, neutrophil absolute count ≥1000/μL, platelets ≥ 75,000 /μL,Total bilirubin ≤1.5 x upper limit of normal (ULN), alkaline phosphatase, aspartate aminotransferase (AST (SGOT) and alanine aminotransferase (ALT (SGPT)) ≤2.5 x ULN (if liver metastasis is present, ≤5 x ULN), Serum albumin≥2.8g/dl, Serum creatinine ≤1.5 x ULN or calculated creatinine clearance >50mL/min (calculated according to Cockcroft Gault formula)
• International Normalized Ratio (INR) or activated partial thromboplastin time (APTT) <1.5 x ULN (thromboembolic event must be ruled out if D-dimer is abnormal)
• Negative pregnancy test not more than 7 days before enrollment,Pregnancy tests can only be omitted in women who do not have any reproductive potential (e.g., postmenopausal women, i.e. amenorrhea ≥2 years or prior hysterectomy or bilateral oophorectomy). Fertile women and men must consent to the use of appropriate contraception at the time of enrollment and during study participation for at least 3 months after the last treatment
• Have sufficient understanding ability and be willing to sign written informed consent

Exclusion criteria

• Pregnant and lactating women
• The patient has experienced hyperprogression and immunotherapy related grade 3 or above adverse reactions during previous immunotherapy
• Received antitumor chemotherapy or biotherapy within 28 days prior to the first use of the investigational drug, the total area of previous bone marrow radiation therapy exceeds 30%; the exception is that if it is not the target lesion, palliative radiotherapy is allowed, and the radiotherapy area must be less than 25% of the bone marrow area
• Suffering from other malignant tumors within the past 5 years or simultaneously
• Suffering from severe neurological and psychiatric disorders
• Patients with uncontrolled or symptomatic brain metastases
• Patients with active autoimmune diseases
• Immunosuppressive or systemic hormone therapy for immunosuppressive purposes (dose >10mg/ day prednisone or other therapeutic hormone) within 14 days prior to initiation of study therapy
• Allergies to investigational drugs or excipients
• Hypertension that cannot be controlled by antihypertensive drugs, coronary heart disease, heart failure, and arrhythmia (QTcF prolongation,>450ms in males and>470ms in females)
• Severe infection in the 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumoniaOral or intravenous administration of therapeutic antibiotics within 2 weeks prior to initiation of study treatment (patients receiving prophylactic antibiotics, for example, to prevent urinary tract infections or exacerbation of chronic obstructive pulmonary disease are eligible for study participation)
• Patients with congenital or acquired immune deficiency (such as HIV infection)
• Have received live attenuated vaccines within 28 days prior to initiation of study treatment, or are expected to require such vaccines during sintilimab treatment or within 60 days after the last administration of sintilimab

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-sen Memorial Hospital,Sun Yat-sen University — Guangzhou

Identifiers

NCT: NCT06365008 · SYSKY-2024-210-04

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗