An Open-label, Multicentre, Phase II Study to Evaluate the Safety and Efficacy of Irinotecan Liposome Injection in Patients With Advanced Biliary Tract Cancer
Overview
- Phase
- Phase 2
- Intervention
- Irinotecan Liposome Injection
- Conditions
- Advanced Biliary Tract Cancer
- Sponsor
- CSPC Ouyi Pharmaceutical Co., Ltd.
- Enrollment
- 17
- Locations
- 1
- Primary Endpoint
- Objective Response Rate (ORR)
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
This study is an open-label, phase II study of irinotecan liposome injection in patients with advanced biliary tract cancer. The purpose of this study is to evaluate the safety, efficacy and pharmacokinetics of irinotecan liposome injection in patients with advanced biliary tract cancer.
Detailed Description
This is an open-label, parallel, multicentre, phase II study to evaluate the efficacy and safety of irinotecan liposome injection. Eligible patients will be divided into two cohorts according to the criteria for the corresponding cohort. The patients in cohort 1 will receive irinotecan liposome injection combined with 5-Fluorouracil (5-FU) and Leucovorin (LV). The patients in cohort 2 will receive irinotecan liposome injection combined with a PD-1 inhibitor, 5-Fluorouracil and Leucovorin.
Investigators
Eligibility Criteria
Inclusion Criteria
- •At least 18 years of age, regardless of gender. 2.Histologically or cytologically confirmed unresectable, locally advanced, or metastatic adenocarcinoma of biliary tract, including intrahepatic cholangiocarcinoma (IHCC), extrahepatic cholangiocarcinoma (EHCC) and gallbladder carcinoma (GBC).
- •3.At least one measurable lesion according to RECIST 1.
- •4.Previous first-line standard system chemotherapy failed. First-line standard chemotherapy is defined as gemcitabine combined with capecitabine or platinum.
- •5.Patients with prior local treatment (embolization, chemoembolization, radiofrequency ablation, or radical radiotherapy) must be completed at least 4 weeks before the first administration of the study drug, palliative decompensated radiotherapy (such as bone metastases) must be completed at least 2 weeks before the first administration of the study drug.
- •6.Eastern Cooperative Oncology Group (ECOG) performance status 0 to
- •7.Life expectancy \>3 months. 8.Adverse reactions must recover to grade 1 or baseline according to CTCAE 5.0 (except for toxicity such as alopecia, grade 2 or less sensory neuropathy, etc., which have been judged no safety risk by investigators).
- •9.Patients should not receive cell growth factors or blood and platelet transfusion within 7 days before the initiate administration of study drug, and laboratory test should meet the following criteria: neutrophile count ≥1.5×10\^9/L;platelet count ≥90×10\^9/L; hemoglobin ≥90 g/L or ≥5.6 mmol/L;serum creatinine ≤1.5×ULN or creatinine clearance rate must be ≥ 50 mL/min when serum creatinine \>1.0×ULN;total bilirubin ≤1.5×ULN; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN or ≤2.5×ULN if intrahepatic lesions exist;Albumin ≥3 g/dL.
- •Activated Partial Thromboplastin Time (APTT), International Normalized Ratio (INR) and prothrombin time (PT) ≤1.5 × ULN for patients not receiving therapeutic anticoagulation.
- •11.Patients with biliary obstruction or no evidence of persistent infection should receive adequate biliary drainage; active or suspected infections are not allowed.
- •Female patients with reproductive potential must agree to use adequate contraception from the signing of informed consent to at least 6 months after the study completion and have a negative serum pregnancy test within 7 days before enrollment, and must be non-lactating. Male patients must agree to use medically approved contraception during the study and for 6 months after the study period.
Exclusion Criteria
- •Patients with definite positive NTRK fusion gene.
- •Patients who have received any investigational drug within 4 weeks prior to the first dose of irinotecan liposomes injection.
- •Patients with definite metastatic encephalopathy.
- •Patients who have received liver transplantation or liver metastases accounted for 50% or more of the total liver volume.
- •Patients with hepatic encephalopathy.
- •Uncontrolled third lacunar effusion other than ascites (e.g., large pleural or pericardial effusion).
- •Previous malignancies in the past five years (except radically resected and non-recurring basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder carcinoma, local prostate carcinoma, carcinoma in situ of cervical, or other carcinoma in situ).
- •History of serious cardiovascular disease.
- •Patients with uncontrolled active bleeding.
- •Gastrointestinal diseases of clinical significance, such as bleeding, inflammation, obstruction, \>grade 1 diarrhea, etc.
Arms & Interventions
Cohort 1: Irinotecan Liposome Injection + 5-FU/LV
The patients in cohort 1 will receive irinotecan liposome injection combined with 5-Fluorouracil (5-FU) and Leucovorin (LV) intravenously on days 1 of every 14-day cycle until disease progression or unacceptable toxicity, or termination of the study for other reasons.
Intervention: Irinotecan Liposome Injection
Cohort 1: Irinotecan Liposome Injection + 5-FU/LV
The patients in cohort 1 will receive irinotecan liposome injection combined with 5-Fluorouracil (5-FU) and Leucovorin (LV) intravenously on days 1 of every 14-day cycle until disease progression or unacceptable toxicity, or termination of the study for other reasons.
Intervention: Fluorouracil
Cohort 1: Irinotecan Liposome Injection + 5-FU/LV
The patients in cohort 1 will receive irinotecan liposome injection combined with 5-Fluorouracil (5-FU) and Leucovorin (LV) intravenously on days 1 of every 14-day cycle until disease progression or unacceptable toxicity, or termination of the study for other reasons.
Intervention: Leucovorin
Cohort 2: Irinotecan Liposome Injection + SG001 + 5-Fu/LV
The patients in cohort 1 will receive irinotecan liposome injection combined with SG001, 5-Fluorouracil (5-FU) and Leucovorin (LV) intravenously on days 1 of every 14-day cycle until disease progression or unacceptable toxicity, or until 24 months is reached, or the study is terminated for other reasons.
Intervention: Irinotecan Liposome Injection
Cohort 2: Irinotecan Liposome Injection + SG001 + 5-Fu/LV
The patients in cohort 1 will receive irinotecan liposome injection combined with SG001, 5-Fluorouracil (5-FU) and Leucovorin (LV) intravenously on days 1 of every 14-day cycle until disease progression or unacceptable toxicity, or until 24 months is reached, or the study is terminated for other reasons.
Intervention: SG001
Cohort 2: Irinotecan Liposome Injection + SG001 + 5-Fu/LV
The patients in cohort 1 will receive irinotecan liposome injection combined with SG001, 5-Fluorouracil (5-FU) and Leucovorin (LV) intravenously on days 1 of every 14-day cycle until disease progression or unacceptable toxicity, or until 24 months is reached, or the study is terminated for other reasons.
Intervention: Fluorouracil
Cohort 2: Irinotecan Liposome Injection + SG001 + 5-Fu/LV
The patients in cohort 1 will receive irinotecan liposome injection combined with SG001, 5-Fluorouracil (5-FU) and Leucovorin (LV) intravenously on days 1 of every 14-day cycle until disease progression or unacceptable toxicity, or until 24 months is reached, or the study is terminated for other reasons.
Intervention: Leucovorin
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: Up to six months after the last patient's first administration
The percentage of patients who achieve a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Secondary Outcomes
- Progression-Free Survival (PFS)(Up to six months after the last patient's first administration)
- Disease Control Rate (DCR)(Up to six months after the last patient's first administration)
- UGT1A1(Within 3 days before the first dose)
- Overall survival (OS)(Up to six months after the last patient's first administration)
- Incidence of treatment-related adverse events (AEs) and serious adverse events (SAEs)(Up to six months after the last patient's first administration)
- Peak Plasma Concentration(0-240 h of circle 1 to circle 4)
- Duration of Response (DOR)(Up to six months after the last patient's first administration)
- Area under the plasma concentration versus time curve(0-240 h of circle 1 to circle 4)