Locally advanced or metastatic, non resectable, adenocarcinoma of the biliary tract including intrahepatic and extrahepatic bile duct MedDRA version: 21.1 Level: LLT Classification code 10025734 Term: Malignant neoplasm of biliary tract, part unspecified System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10008593 Term: Cholangiocarcinoma System Organ Class: 10029104 - Neoplasms benign, malignant
Conditions
Interventions
Trade Name: Onivyde
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Nal-IRI
Other descriptive name: IRINOTECAN HYDROCHLORIDE TRIHYDRATE
Concentration unit: mg/ml millig
Sponsors
AIO-Studien-gGmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent including participation in translational research and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations 2. Age = 18 years at time of study entry 3. Histologically confirmed, non-resectable, locally advanced or metastatic adenocarcinoma of the intrahepatic or extrahepatic biliary tract 4. Non-resectability has to be stated by local interdisciplinary tumor board 5. Measurable or assessable disease according to RECIST 1.1 6. ECOG performance status 0-1 7. Life expectancy of more than 3 months 8. If applicable, adequately treated biliary tract obstruction before study entry with total bilirubin concentration = 2 x ULN 9. Adequate blood count, liver-enzymes, and renal function: • White blood cell count = 3.5 x 106/mL • Platelet count = 100 x 109/L (>100,000 per mm3) • AST (SGOT)/ALT (SGPT) = 5 x institutional upper limit of normal • Serum Creatinine = 1.5 x institutional ULN and a calculated glomerular filtration rate = 30 mL per minute 10. Patients not receiving therapeutic anticoagulation must have an INR =65 years) yes F.1.3.1 Number of subjects for this age range 46
Exclusion criteria
Exclusion criteria: 1. Active uncontrolled infection, chronic infectious diseases, immune deficiency syndromes 2. Premalignant hematologic disorders, e.g. myelodysplastic syndrome 3. Clinically significant cardiovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) within 6 months before enrollment 4. Prior (<3 years) or concurrent malignancy (other than biliary-tract cancer) which either progresses or requires active treatment. Exceptions are: basal cell cancer of the skin, pre-invasive cancer of the cervix, T1a or T1b prostate carcinoma, or superficial urinary bladder tumor [Ta, Tis and T1]. 5. Pre-existing lung disease 6. History or clinical evidence of CNS metastases Exceptions are: Subjects who have completed local therapy and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids 6 weeks prior to start of study treament. Screening with CNS imaging (CT or MRI) is required only if clinically indicated or if the subject has a history of CNS metastases 7. History of hypersensitivity to any of the study drugs or any of the constituents of the products 8. Known dihydropyrimidine dehydrogenase (DPD) deficiency 9. Allogeneic transplantation requiring immunosuppressive therapy or other major immunosuppressive therapy 10. Severe non-healing wounds, ulcers or bone fractions 11. Evidence of bleeding diathesis or coagulopathy 12. Major surgical procedures, except open biopsy, nor significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgical procedure during the course of the study except for surgery of central intravenous line placement for chemotherapy administration. 13. Medication that is known to interfere with any of the agents applied in the trial. 14. Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year). [Acceptable methods of contraception are: implants, injectable contraceptives, combined oral contraceptives, intrauterine pessars (only hormonal devices), sexual abstinence or vasectomy of the partner]. Women of childbearing potential must have a negative pregnancy test (serum ß-HCG) at Screening. 15. Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results 16. Known Gilbert-Meulengracht syndrome 17. Known chronic hypoacusis, tinnitus or vertigo 18. Participation in another clinical study with an investigational product during the last 30 days before inclusion or 7 half-lifes of previously used trial medication, whichever is of longer duration. 19. Previous enrollment or randomization in the present study (does not include screening failure). 20. Any other chemotherapy at study start 21. Involvement in the planning and/or conduct of the study (applies to both Servier staff and/or staff of sponsor and study site) 22. Patient who might be dependent on the sponsor, site or the investigator 23. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG. 24. Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether a combination of 5-FU and nal-IRI prolongs progression-free survival in patients with locally advanced or metastatic adenocarcinoma of the biliary tract ;Secondary Objective: •Overall progression free survival according to RECIST 1.1 •Overall survival •Disease control rate according to RECIST 1.1 •Proportion of patients with an objective response according to RECIST 1.1 •Toxicity/Safety according to CTC-AE-criteria (= Grade 3/4) •Health related quality of life, anxiety and depression status (EORTC QLQ-BIL21, QLQ-C30 and HADS-D questionnaires) •Retrospective correlation of resectability in accordance with a central surgical board compared to local surgical review •Retrospective central radiological review ;Primary end point(s): Progression-free survival rate at 4 months defined as the proportion of patients with non-progressive disease 4 months after randomization by intention to treat analysis;Timepoint(s) of evaluation of this end point: 4 months after randomization | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall Progression-free survival • 3-years overall survival • Disease control rate according to RECIST 1.1 after 2 months • Objective tumor response rate (ORR) according to RECIST 1.1 • Toxicity/Safety according to CTC-AE-criteria (= Grade 3/4) • Patient related outcome/Quality of Life/Time to definitive deterioration (TUDD) to be assessed with the following tools: EORTC QLQ-BIL21, QLQ-C30 and HADS-D • Tumor resectability in accordance with a retrospective central surgical board compared to local surgical review • Radiological response according to RECIST 1.1 and volumetry determined by a retrospective central radiological review ;Timepoint(s) of evaluation of this end point: after end of study of patient | — |
Countries
Germany
Contacts
Public ContactDr. Mischo Kursar
AIO-Studien-gGmbH
Outcome results
None listed