search
Back to results

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

Primary Purpose

Gastric Cancer Stage IV

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Oxaliplatin
Levo-Leucovorin
5-fluorouracil
Paclitaxel
Irinotecan
Tislelizumab
Sponsored by
Fujian Cancer Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Cancer Stage IV

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 apatinib 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.

Sites / Locations

  • Fujian cancer hospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

POFI and Tislelizumab

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Overall Response Rate
Clinical response of treatment according to RESIST v1.1 criteria (ORR, objective response rate).
Progression-free survival
The length of time from enrollment until the time of progression of disease (PFS, progression-free survival).
Overall survival
The length of time from enrollment until the time of death (OS, overall survival).

Full Information

First Posted
April 1, 2022
Last Updated
September 15, 2023
Sponsor
Fujian Cancer Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT05319639
Brief Title
Phase I/II Study of the Combination of Irinotecan and POF (POFI) and Tislelizumab
Official Title
Phase I/II Study of the Combination of Irinotecan and POF (Paclitaxel Plus Oxaliplatin Plus 5-fluorouracil Plus Leucovorin) and Tislelizumab
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 16, 2023 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fujian Cancer Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Cancer Stage IV

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
POFI and Tislelizumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
Oxaliplatin will be administered on day 1 of each cycle at 85mg/m2 once every 14 days.
Intervention Type
Drug
Intervention Name(s)
Levo-Leucovorin
Intervention Description
Levo-Leucovorin will be administered on day 1 of each cycle at 200 mg/m2 once every 14 days.
Intervention Type
Drug
Intervention Name(s)
5-fluorouracil
Intervention Description
5-fluorouracil will be administered at 2400 mg/m2 over 46-hour every 14 days.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
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
Intervention Name(s)
Irinotecan
Intervention Description
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
Intervention Name(s)
Tislelizumab
Intervention Description
Tislelizumab will be administered on day 1 of each cycle at 200mg once every 14 days.
Primary Outcome Measure Information:
Title
The maximum dose tolerated
Description
To determine the maximum tolerated dose of POFI with different doses of irinotecan and paclitaxel combined with Tislelizumab in the first month.
Time Frame
1 month
Secondary Outcome Measure Information:
Title
Overall Response Rate
Description
Clinical response of treatment according to RESIST v1.1 criteria (ORR, objective response rate).
Time Frame
2 years
Title
Progression-free survival
Description
The length of time from enrollment until the time of progression of disease (PFS, progression-free survival).
Time Frame
2 years
Title
Overall survival
Description
The length of time from enrollment until the time of death (OS, overall survival).
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
lin rong bo, bachelor
Phone
13705919382
Ext
86
Email
rongbo_lin@163.com
Facility Information:
Facility Name
Fujian cancer hospital
City
Fuzhou
State/Province
Fujian
ZIP/Postal Code
350500
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
lin R bo
Phone
13705919382
Ext
86
Email
rongbo_lin@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs