locally advanced or metastatic pancreatic cancer after failure of a gemcitabine/nab-paclitaxel 1st-line treatment MedDRA version: 21.0 Level: LLT Classification code 10033604 Term: Pancreatic cancer System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10033605 Term: Pancreatic cancer metastatic System Organ Class: 100000004864 MedDRA version: 21.0 Level: LLT Classification code 10033606 Term: Pancreatic cancer non-resectable System Organ Class: 100000004864 Me
Conditions
Interventions
Trade Name: ONIVYDE®
Product Name: nanoliposomal irinotecan
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: irinotecan hydrochloride trihydrate (salt in a pegylated lip
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. Clinical indication for a 2nd-line systemic therapy according to current standard-of-care. 3. Age = 18 years at time of study entry 4. Patients with histologically or cytologically confirmed pancreatic ductal adenocarcinoma 5. Imaging of evaluable lesions (either sonography, X-ray, CT scans, MRI): only in case of treatment failure because of progress 6. ECOG performance status 0-2 7. One line of systemic gemcitabine/Nab-paclitaxel -based therapy for advanced disease (irrespective of prior adjuvant therapy) OR Previous adjuvant gemcitabine/Nab-paclitaxel-based chemotherapy with documented progression less than 6 months after termination 8. Documentation of prior therapy (duration, maximum toxicity, reason for discontinuation) 9. Adequate blood count, liver-enzymes, and renal function: • neutrophil count > 1.5 x 10^6/mL • Platelet count = 100 x 10^9/L (=100,000 per mm^3) • AST (SGOT)/ALT (SGPT) = 5 x institutional upper limit of normal • bilirubin =1.5 ULN (=65 years) yes F.1.3.1 Number of subjects for this age range 135
Exclusion criteria
Exclusion criteria: Medical criteria: 1. 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, including but not limited to: a) Active uncontrolled infection, chronic infectious diseases, immune deficiency syndromes b) Premalignant hematologic disorders, e.g. myelodysplastic syndrome c) Clinically significant cardiovascular disease in (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) 6 months before enrollment d) 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]. e) Pre-existing lung disease of clinical significance or with impact on performance status f) History or clinical evidence of CNS metastases Exceptions are: Subjects who have completed local therapy and who meet both of the following criteria: I. are asymptomatic and II. 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 g) Allogeneic transplantation requiring immunosuppressive therapy or other major immunosuppressive therapy h) Severe non-healing wounds, ulcers or bone fractions i) Evidence of bleeding diathesis or coagulopathy j) Major surgical procedures, except open biopsy, or significant traumatic injury within 28 days prior to star of study treatment, 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. k) Known Gilbert-Meulengracht syndrome l) Known chronic hypoacusis, tinnitus or vertigo m) Bone marrow depression (e.g., after radiation therapy) n) Pernicious anemia and other megaloblastic anemias secondary to vitamin B12 deficiency o) Severe impairment of hepatic function p) Diarrhea Drug related criteria: 2. Medication that is known to interfere with any of the agents applied in the trial. 3. Known dihydropyrimidine dehydrogenase (DPD) deficiency with acitivity score of 0.5 or less 4. History of hypersensitivity to any of the study drugs or any of the constituents of the products. 5. Any other efficacious cancer treatment except protocol specified treatment at study start. Safety criteria: 6. 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 (urine or serum ß-HCG acc. to SOC) at Screening. Methodological criteria: 7. Any experimental pretreatment for advanced disease 8. 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 longer, with the following exception: Any clinical study with the IMPs Nab-paclitaxel + gemcitabine and under the c
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Confirmation that longer Time-To-Treatment-Failure (TTF) during first-line treatment is predictive for the benefit of 2nd- line treatment with Nal-IRI combination chemotherapy.;Secondary Objective: Secondary objectives of this study are: • to generate additional efficacy and safety data for the 2nd-line treatment • to assess the Quality of Life and Patient Reported Outcomes during 2nd-line treatment • to asses the impact of the course of the 1st-line treatment on the outcome of the 2nd-line therapy • to explore the impact of physiological and molecular markers on the efficacy of the 2nd-line • to validate a prognostic second-line score accord. to Sinn et al., 2016;Primary end point(s): Time to Treatment Failure of second-line treatment (TTF2) Expected increase of the TTF2 by 50% in the cohort of patients with favorable TTF1 (TTF1 high: upper third of the patient population) as compared to patients with short TTF1 (TTF low: lowest third of the patient population);Timepoint(s) of evaluation of this end point: End of Study (EoS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Overall survival - AEs / SAEs - QoL [EORTC QLQ-PAN26, QLQ-C30; EQ-5D-5L] - Evaluation of time to definitive deterioration of QoL (TDD) - Growth modulation index (GMI) - Second-line score accord. to Sinn et al., 2016;Timepoint(s) of evaluation of this end point: End of Study (EoS) | — |
Countries
Germany
Contacts
Public ContactAIO-Studien-gGmbH
AIO-Studien-gGmbH
Outcome results
None listed