Hepatic Oligometastatic Adenocarcinoma of the Pancreas MedDRA version: 27.0 Level: PT Classification code 10033610 Term: Pancreatic carcinoma metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Onivyde
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: IRINOTECAN
CAS Number: 97682-44-5
Concentration unit: mg/ml milligram(s)/millilitre
Concentration ty
Sponsors
University of Cologne
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed diagnosis of treatment-naïve limited hepatic metastatic adenocarcinoma of the pancreas Definition of limited hepatic metastasis: 1 to 5 metastases in CT/MRI and/or contrast-enhanced ultrasound scan, which are potentially resectable or treatable by ablative procedures.. In the event that more than 5 liver metastases are detected on preoperative imaging, the patient may nevertheless be included based on an individual decision after mandatory consultation with the sponsor. This decision must take into account the complexity of the overall operation of primary tumor and metatstases, and technical resectability of the liver metastases is crucial. (Note 1: Patients also fulfil this inclusion criterion if a hepatic metastasis was partly or entirely removed as part of the diagnosis and is thus not detectable by CT/MRI and/or contrast-enhanced ultrasound scan at screening. Note 2: If more than five metastases are unexpectedly detected during surgery, it is not a violation of this inclusion criterion if the excess metastases had not been detectable by CT/MRI and/or contrast-enhanced ultrasound scan at screening.) 2. Measurable disease according to RECIST v1.1 3. ECOG performance status 0-1 4. Adequate renal, hepatic and bone marrow function, defined as o Calculated creatinine clearance =60 mL/min according to CKD-EPI formula o Total bilirubin =2 mg/dL; patients with biliary stent may be included if bilirubin level decreased to =2 mg/dL after stent insertion o ALT and AST =5 × upper limit of normal (ULN) o Absolute neutrophil count (ANC) =1.5 × 109/L o Thrombocytes =100 × 109/L o Haemoglobin =9 g/dL o aPTT =1.5 × ULN and Quick value =70% 5. Patients =18 years at the time of signing the informed consent 6. Females of childbearing potential (FCBPs) must agree to use highly effective contraceptive measures (Pearl index =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Acinar cell carcinoma and/or neuroendocrine carcinoma of the pancreas 2. Symptomatic clinically significant ascites 3. Evidence of any distant metastases other than limited hepatic metastasis as defined in inclusion criterion 1. 4. Any tumour-specific pretreatment of the adenocarcinoma of the pancreas (including but not limited to surgery, radiation therapy, chemotherapy or ablative procedures) 5. Any malignancies other than adenocarcinoma of the pancreas in the 5 years before the start of the clinical trial except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, breast cancer, prostate cancer or superficial bladder tumours (Ta, Tis and T1) 6. Hypersensitivity to any of the IMPs or any of the excipients 7. Any major surgery within 4 weeks before the first IMP administration 8. Pregnant or breast-feeding female 9. Known chronic inflammatory bowel disease, bowel obstruction, chronic diarrhea, Grade =2 according to NCI CTCAE version 5.0 10. Peripheral polyneuropathy, Grade = 2 according to NCI CTCAE version 5.0 11. Known interstitial lung disease or pulmonary fibrosis 12. Radiographic evidence of severe portal hypertension 13. Liver cirrhosis = Child Pugh B 14. Cholestasis or cholangitis despite adequate biliary stenting; treatment with anti-infectious agents is permitted; patient must be disease-free and without anti-infectious treatment for 7 days before the first IMP administration 15. Active infection requiring systemic therapy 16. Known HIV seropositivity 17. Active or chronic Hepatitis B or Hepatitis C infection 18. Known glucoronidation deficiency (Gilbert’s syndrome) (specific screening not required) 19. Known complete dihydropyrimidine dehydrogenase (DPD) deficiency (specific screening according to the recommendations of the SmPC in effect for 5-FU; patients with a known complete DPD deficiency must be excluded; patients with a known partial DPD deficiency may be included at the discretion of the investigator 20. Clinically significant cardiovascular or vascular disease or disorder =6 months before enrolment into the clinical trial (e.g., myocardial infarction, unstable angina pectoris, chronic heart failure NYHA = Grade 2, uncontrolled arrhythmia, cerebral infarction) 21. Pulmonary embolism, deep venous thrombosis or arterial thromboembolism =1 months before the first IMP administration 22. Any other severe concomitant disease or disorder, which could influence patient’s ability to participate in the clinical trial and his/her safety during the trial or interfere with interpretation of results; e.g., severe hepatic, renal, pulmonary, cardiovascular, metabolic or psychiatric disorders 23. Requirement for live vaccination within 4 weeks before the first IMP administration and during neoadjuvant chemotherapy 24. Use of strong CYP3A4 inhibitors (Strong CYP3A4 inhibitors have to be discontinued at least one week prior to start of trial treatment.) Use of strong UGT1A1 inhibitors or strong CYP3A4 inducers unless there are no therapeutic alternatives 25. Treatment with nucleoside analogues such as brivudine within 4 weeks before the first IMP administration or requirement for concomitant antiviral treatment with brivudine or analogues 26. Participation in a clinical trial or experimental drug treatment within 4 weeks before the first IMP administration or within a period of 5 half-lives of the substances administered in a clinical trial or during an experimental drug treatment before the f
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of neoadjuvant NAPOX chemotherapy followed by R0/R1 resection in patients with hepatic oligometastatic adenocarcinoma of the pancreas;Secondary Objective: Secondary Objectives •To determine efficacy and safety of the treatment concept •To determine health-related quality of life (HR QoL) Other Exploratory Objectives •To analyse HR QoL-adjusted overall survival ;Primary end point(s): Overall survival after R0/R1 resection (OS-res) (only patients with R0/R1 resection);Timepoint(s) of evaluation of this end point: Overall survivall will be evaluated in a continously until end of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy • R0/R1 resection rate after neoadjuvant chemotherapy • Overall survival (OS) • Progression-free survival (PFS) after R0/R1 resection according to RECIST v1.1 Safety • Type, frequency and severity of adverse events with severity according to NCI CTCAE version 5.0 (neoadjuvant chemotherapy) • Perioperative morbidity and mortality Health-related quality of life • HR-QoL according to EORTC QLQ C30 and EORTC QLQ PAN26 questionnaires Other, exploratory endpoints • HR QoL-adjusted OS;Timepoint(s) of evaluation of this end point: - R0/R1 resection rate will be evaluated after resection - OS will be evaluated continiously until end of study - PFS will be evaluated every 4 cycles (every 8 weeks) during study treatment and according to lokal standard in Follow Up - Adverse events will be evaluated continously during study treatment - perioperative morbidity and mortality will be evaluated continously from resection until 12 weeks afterwards - Quality-of-life will be evaluated every second cycle, at end of treatment and at post surgery vivist (if surgery was performed) | — |
Countries
Germany
Contacts
Public ContactStudiensekretariat
University of Cologne
Outcome results
None listed