ano-liposomal Irinotecan plus Fluorouracil for treatment of biliary tract cancer
- Conditions
- Neoplasms
- Registration Number
- KCT0003022
- Lead Sponsor
- Asan Medical Center
- Brief Summary
Between September 5, 2018 and February 18, 2020, 174 patients were randomly assigned (median follow-up 11·8 months [IQR 7·7–18·7]). The nal-IRI+5-FU/LV group had a significantly longer median PFS per BICR (7·1 vs 1·4 months; HR 0·56 [95% CI 0·39–0·81], p=0·0019), median PFS per investigator review (3·9 vs 1·6 months; HR 0·48 [0·34–0·69], p<0·0001), and median OS (8·6 vs 5·5 months; HR 0·68 [0·48–0·98], p=0·0349) than the 5-FU/LV group. ORRs in the nal-IRI+5-FU/LV and the 5-FU/LV groups were 14·8% and 5·8% per BICR (p=0·0684) and 19·3% and 2·3% per investigator review (p=0·0002), respectively. Grade? 3 adverse events were reported in 77·3% of the nal-IRI+5-FU/LV group and 31·4% of the 5-FU/LV group.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 174
1.Signed and written informed consent form
2.= 19 years of age
3.Histologically or cytologically confirmed cholangiocarcinoma
4.Documented metastatic disease
5.At least one measurable lesion according to the RECIST v1.1
6.Disease progression on gemcitabine-cisplatin combination therapy
7.For patients whose disease recurred after curative resection (R0 or R1), previous adjuvant 5-FU-based chemotherapy is allowed if there is at least 6 month-interval between the last dose of adjuvant chemotherapy and recurrence of disease.
8.Adequate hepatic, renal and hematological function AST(Aspartate Aminotransferase), ALT(Alanine Aminotransferase) = 100 IU/L (100 U/L), Cr(Creatinine) = 1.5mg/dL
9.Eastern Cooperative Oncology Group (ECOG) Performance status 0-1
1.Serum total bilirubin =2 x ULN(upper limit of normal) (biliary drainage is allowed for biliary obstruction)
2.Severe renal impairment (Clcr = 30 ml/min)
3.Inadequate bone marrow reserves as evidenced by:
?ANC(Absolute Neutrophile Count) = 1,500 cells/µl; or
?Platelet count = 100,000 cells/µl; or
?Hemoglobin = 9 g/dL
4.ECOG performance status 2-4
5.Any clinically significant disorder impacting the risk-benefit balance negatively per physician's judgment
6.Any clinically significant gastrointestinal disorder, including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > grade 2
7.Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) in last 6 months
8.NYHA(New York Heart Association) Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure. Or known abnormal ECG with clinically significant abnormal findings
9.Active infection or an unexplained fever >38.5°C (excluding tumor fever), which in the physician's opinion might compromise the patient's health
10.Current use or any use in last two weeks of strong CYP3A-enzyme inducers/inhibitors and/or strong UGT1A inhibitors
11.Known hypersensitivity to any of the components of Onivyde other liposomal irinotecan formulations, irinotecan, fluoropyrimidines, or leucovorin.
12.Breast feeding, known pregnancy, positive serum pregnancy test or unwillingness to use an effective method of contraception, during therapy and for 3 months following the last dose of Onivyde. Females of Childbearing Potential must either agree to use and be able to take effective contraceptive birth control measures (Pearl Index < 1) or agree to practice complete abstinence from heterosexual intercourse during the course of the study and for at least 3 months after last application of program treatment. A female subject is considered to be of childbearing potential unless she is age = 50 years and naturally amenorrhoeic for = 2 years, or unless she is surgically sterile. Males must agree not to father a child (including not donating sperm) during the course of the trial and for at least 6 months after last administration of study drugs.
13.Previous treatment with combination drug tegafur, gimeracil, and oteracil potassium with seven days before enrollment.
14.Current treatment with Sorivudine.
15.Patients who are seriously debilitated or are suffering from bone marrow depression after radiotherapy or treatment with other antineoplastic agents.
16.Pregnancy or women with child-bearing potential or lactating.
17. Non-malignant severe co-morbidity
18. Previous second-line anti-cancer therapy (e.g., Tegafur)
19. History of other malignancy with a disease-free interval <5 years (Registration is permitted if it has minimal impact on prognosis, such as carcinoma in situ and papillary thyroid cancer)
20. History or current eveidence of brain metastasis
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression-free survival by independent central review
- Secondary Outcome Measures
Name Time Method Response rates determined by the investigator according to the Response Evaluation Criteria in Solid Tumors(RECIST) V1.1;Adverse events according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) V4.03;Overall survival;European Organization for Research and Treatment of Cancer - Quality of life Questionnaire(EORTC QLQ) C-30;Progression-free survival by investigator assessment;Biomarker analysis