Phase I/II Study of the Combination of Irinotecan and POF (POFI) and Tislelizumab

NCT05319639 | Recruiting Phase 1

• 1 other identifier: SYLT-023
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the phase I/II study is to establish the safety of Combination of Irinotecan and paclitaxel with 5-FU, leucovorin, oxaliplatin and Tislelizumab.

Conditions

Gastric Cancer Stage IV

Outcome Measures

Primary Outcomes (1)

• The maximum dose tolerated

  To determine the maximum tolerated dose of POFI with different doses of irinotecan and paclitaxel combined with Tislelizumab in the first month.

  1 month

Secondary Outcomes (3)

• Overall Response Rate

  2 years

• Progression-free survival

  2 years

• Overall survival

  2 years

Study Arms (1)

POFI and Tislelizumab

EXPERIMENTAL

This study will include a sequential evaluation of 3 subjects per cohort. Irinotecan 135 → 150 and paclitaxel 45 → 67.5 → 90 mg/m2 on day 1. The rest of regimen is that oxaliplatin (85 mg/m2) and Lev-leucovolin (200 mg/m2).Subsequently, a 46-hour infusion of fluorouracil (2400 mg/m2) was administered using an ambulatory pump, repeating the cycle every 14 days. Tislelizumab 200mg，repeating the cycle every 14 days. A dose limiting toxicity (DLT) event is defined as any of the following events in the first 4-week period: CTCAE Grade 4 event (except for neutropenia lasting for ≤ 5 days); Grade 3 non-hematologic toxicity (except for nausea and vomiting that could be improved with optimal supportive care, escalation of alkaline phosphatase) If a DLT is experienced in any cohort, the cohort will be expanded to 6 subjects. If 2 DLTs are experienced in any cohort, the dose escalation ceased. The MTD was defined as the dose having at most two out of six patients experience DLT.

Drug: Oxaliplatin; Drug: Levo-Leucovorin; Drug: 5-fluorouracil; Drug: Paclitaxel; Drug: Irinotecan; Drug: Tislelizumab

Interventions

Oxaliplatin DRUG

Oxaliplatin will be administered on day 1 of each cycle at 85mg/m2 once every 14 days.

POFI and Tislelizumab

Levo-Leucovorin DRUG

Levo-Leucovorin will be administered on day 1 of each cycle at 200 mg/m2 once every 14 days.

POFI and Tislelizumab

5-fluorouracil DRUG

5-fluorouracil will be administered at 2400 mg/m2 over 46-hour every 14 days.

POFI and Tislelizumab

Paclitaxel DRUG

Paclitaxel will be administered on day 1 of each cycle at 45mg/m2 at dose level 1; 67.5 mg/m2 at dose level 2 ; 90 mg/m2 at dose level 3; 112.5 mg/m2 at dose level 4 once every 14 days.

POFI and Tislelizumab

Irinotecan DRUG

Irinotecan will be administered on day 1 of each cycle at 135 mg/m2 at dose level 1; 150 mg/m2 at dose level 2 once every 14 days.

POFI and Tislelizumab

Tislelizumab DRUG

Tislelizumab will be administered on day 1 of each cycle at 200mg once every 14 days.

POFI and Tislelizumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with advanced unresectable, histologically confirmed adenocarcinoma of the gastric or gastroesophageal junction.
• With or without measurable lesions.
• Patients must have a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale.
• Without serious system dysfunction and could tolerate chemotherapy. With normal marrow, liver and renal function: a hemoglobin (HGB) of ≥100g/L (without blood transfusion during 14 days); a leucopenia count of ≥4.0×109/L; a platelet count of ≥100×109/L; a total bilirubin (TBil) of ≤1.5 upper normal limitation (UNL); a creatinine (Cr) of ≤ 1.5 UNL; a creatinine clearance rate ≥ 50ml/min (Cockcroft-Gault); a alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) of ≤2.5 UNL or ≤5 UNL in case of liver metastasis.
• Life expectancy ≥3 months.
• With normal electrocardiogram results and no history of congestive heart failure.
• With normal coagulation function: activated partial thromboplastin time (APTT), prothrombin time (PT) and INR, each ≤ 1.5 x ULN.
• Female subjects of child-bearing potential must agree to use contraceptive measures starting 1 week before the administration of the first dose of Tislelizumab until 8 weeks after discontinuing study drug. Male subjects must agree to use contraceptive measures during the study and 8 weeks after last dose of study drug
• With written informed consent signed voluntarily by patients themselves or their supervisors witted by doctors.
• With good compliance and agree to accept follow-up of disease progression and adverse events.

You may not qualify if:

• Patients with a history of another neoplastic disease within the past three years, excluding basal cell carcinoma of the skin, cervical carcinoma in situ, or nonmetastatic prostate cancer.
• Patients with brain or central nervous system metastases, including leptomeningeal disease.
• Pregnant (positive pregnancy test) or breast feeding.
• Serious, non-healing wound, ulcer, or bone fracture.
• Significant cardiac disease as defined as: unstable angina, New York Heart Association (NYHA) grade II or greater, congestive heart failure, history of myocardial infarction within 6 months Evidence of bleeding diathesis or coagulopathy.
• History of a stroke or CVA within 6 months.
• Clinically significant peripheral vascular disease.
• Inability to comply with study and/or follow-up procedures.
• Patients with any other medical condition or reason, in that investigator's opinion, makes the patient unstable to participate in a clinical trial.

Sponsors & Collaborators

• Fujian Cancer Hospital: lead

Study Sites (1)

Fujian cancer hospital

Fuzhou, Fujian, 350500, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Oxaliplatin; Levoleucovorin; Fluorouracil; Paclitaxel; Irinotecan; tislelizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Leucovorin; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Camptothecin; Alkaloids

Central Study Contacts

lin rong bo, bachelor

CONTACT

13705919382; rongbo_lin@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2022
• First Posted: April 8, 2022
• Study Start: February 16, 2023
• Primary Completion: October 31, 2024
• Study Completion: December 31, 2025
• Last Updated: February 27, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)