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

NCT ID: NCT05319639

Last Updated: 2025-02-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-16
• Study Completion Date: 2025-12-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

POFI and Tislelizumab

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.

Group Type: EXPERIMENTAL

Oxaliplatin

Intervention Type: DRUG

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

Levo-Leucovorin

Intervention Type: DRUG

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

5-fluorouracil

Intervention Type: DRUG

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

Paclitaxel

Intervention Type: 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.

Irinotecan

Intervention Type: 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.

Tislelizumab

Intervention Type: DRUG

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

Interventions

Oxaliplatin

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

Intervention Type: DRUG

Levo-Leucovorin

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

Intervention Type: DRUG

5-fluorouracil

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

Intervention Type: DRUG

Paclitaxel

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.

Intervention Type: DRUG

Irinotecan

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.

Intervention Type: DRUG

Tislelizumab

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients with advanced unresectable, histologically confirmed adenocarcinoma of the gastric or gastroesophageal junction.

2. With or without measurable lesions.

3. Patients must have a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale.

4. 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.

5. Life expectancy ≥3 months.

6. With normal electrocardiogram results and no history of congestive heart failure.

7. With normal coagulation function: activated partial thromboplastin time (APTT), prothrombin time (PT) and INR, each ≤ 1.5 x ULN.

8. 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

9. With written informed consent signed voluntarily by patients themselves or their supervisors witted by doctors.

10. With good compliance and agree to accept follow-up of disease progression and adverse events.

Exclusion Criteria

1. 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.

2. Patients with brain or central nervous system metastases, including leptomeningeal disease.

3. Pregnant (positive pregnancy test) or breast feeding.

4. Serious, non-healing wound, ulcer, or bone fracture.

5. 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.

6. History of a stroke or CVA within 6 months.

7. Clinically significant peripheral vascular disease.

8. Inability to comply with study and/or follow-up procedures.

9. Patients with any other medical condition or reason, in that investigator's opinion, makes the patient unstable to participate in a clinical trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fujian Cancer Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Fujian cancer hospital

Fuzhou, Fujian, China

Site Status: RECRUITING

Countries

China

Central Contacts

lin rong bo, bachelor

Role: CONTACT

rongbo_lin@163.com

13705919382 ext. 86

Facility Contacts

lin R bo

Role: primary

rongbo_lin@163.com

13705919382 ext. 86

Other Identifiers

SYLT-023

Identifier Type: -

Identifier Source: org_study_id