Sintilimab Plus FOLFIRI as Salvage Therapy for Patients With Advanced Gastric Cancer

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

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 salvage therapy for patients diagnosed with 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 progression-free survival (PFS). The investigators estimated that 40 patients were necessary. Secondary endpoints include overall survival, objective response rate, disease control rate and safety for unresectable or metastatic gastric cancer.

Study Overview

• Status: Recruiting
• Conditions: Unresectable/Metastatic Gastric Cancer
• Intervention / Treatment: Drug: Sintilimab+irinotecan+leucovorin folinate+fluorouracil

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Qiong Yang, Doctor; Phone Number: 13632341201; Email: yangqiong05@126.com
• Study Contact Backup: Name: Yajing Liu, Doctor; Phone Number: 13631327315; Email: liuyajing1030@126.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Sun Yat-sen Memorial Hospital,Sun Yat-sen University
      • Contact: Qiong Yang, Doctor; Phone Number: 13632341201; Email: yangqiong05@126.com
      • Contact: Yajing Liu, Doctor; Phone Number: 13631327315; Email: liuyajing1030@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Metastatic or locally advanced, unresectable gastric adenocarcinoma confirmed by histology or cytology
2. Progression or toxicity intolerance of first-line treatment
3. Age 18-75 years old
4. ECOG score 0-2
5. Estimated life expectancy of at least 12 weeks
6. 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)
7. 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)
8. 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
9. Have sufficient understanding ability and be willing to sign written informed consent

Exclusion Criteria:

1. Pregnant and lactating women
2. The patient has experienced hyperprogression and immunotherapy related grade 3 or above adverse reactions during previous immunotherapy
3. 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
4. Suffering from other malignant tumors within the past 5 years or simultaneously
5. Suffering from severe neurological and psychiatric disorders
6. Patients with uncontrolled or symptomatic brain metastases
7. Patients with active autoimmune diseases
8. 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
9. Allergies to investigational drugs or excipients
10. Hypertension that cannot be controlled by antihypertensive drugs, coronary heart disease, heart failure, and arrhythmia (QTcF prolongation,>450ms in males and>470ms in females)
11. 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)
12. Patients with congenital or acquired immune deficiency (such as HIV infection)
13. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	PFS is defined as the time from study enrollment to first disease progression or death, whichever occurs first	Undergo imaging examination to evaluate efficacy every 8 weeks ±7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	OS is defined as the time from study enrollment to the date of death due to any cause	From the date of enrollment to the date of death from any cause
Objective response rate	ORR is defined as the percentage of patients relative to the total of enrolled subjects who achieve a complete response (CR) or partial response (PR) based on CT or MRI scan images	Undergo imaging examination to evaluate efficacy every 8 weeks ±7 days
Disease control rate	DCR is defined as the percentage of patients relative to the total of enrolled subjects who achieve a complete response (CR) , partial response (PR) or stable disease (SD) based on CT or MRI scan images	Undergo imaging examination to evaluate efficacy every 8 weeks ±7 days
Adverse Events	Assessment of Safety and tolerance for sintilimab plus FOLFIRI as salvage therapy in patients with unresectable/metastatic gastric cancer, including incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI CTC AE Version 5.0.	from the date of the first medicine to 28±7 days after the last medicine

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Investigators: Principal Investigator: Qiong Yang, Doctor, Sun Yat-sen Memorial Hospital,Sun Yat-sen University; Principal Investigator: Yajing Liu, Doctor, Sun Yat-sen Memorial Hospital,Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): April 8, 2024
• Primary Completion (Estimated): April 8, 2027
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: April 10, 2024
• First Submitted That Met QC Criteria: April 10, 2024
• First Posted (Estimated): April 15, 2024

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Sintilimab; salvage therapy; FOLFIRI
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Leucovorin; Irinotecan
• Other Study ID Numbers: SYSKY-2024-210-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No