First-line Therapy in Metastatic PDAC

Exclusion Criteria

• •Locally advanced PDAC without metastasis
• •Symptomatic/clinically significant ascites (expected indication for repeated paracentesis)
• •Known metastatic disease to the brain. Brain imaging is required in symptomatic patients to rule out brain metastases, but is not required in asymptomatic patients.
• •Previous palliative chemotherapy or other palliative systemic tumor therapy for metastatic disease of PDAC
• •Previous gemcitabine or 5-FU based treatment with exception of gemcitabine/fluoropyrimidine based treatment applied in the neoadjuvant or adjuvant setting (before/after potential curative R0 or R1 resection) and if the neoadjuvant/adjuvant chemotherapy was terminated at least 6 months before randomization
• •Previous radiotherapy of PDAC with exception of radiotherapy in the context of a neoadjuvant or adjuvant treatment setting that was terminated at least 6 months before randomization
• •Any major surgery within the last 4 weeks before randomization
• •Clinically significant decrease in performance status within 2 weeks of intended first administration of study medication (by medical history)
• •Severe tumor-related cachexia and/or known weight loss \> 15% within one month before study enrollment
• •Pre-existing polyneuropathy ≥ grade 2 according to CTCAE version 4.03
• •Gastrointestinal disorders that might interfere with the absorption of the study drug and gastrointestinal disorders with diarrhoea as a major symptom (e.g. Crohn's disease, malabsorption), and chronic diarrhoea of any aetiology CTCAE version 4.03 grade ≥ 2
• •Any other severe concomitant disease or disorder, which could influence patient's ability to participate in the study and his/her safety during the study or interfere with interpretation of study results e.g. active infection, uncontrolled hypertension, clinically significant cardiovascular disease e.g. cerebrovascular accident (≤ 6 months before study start), myocardial infarction (≤ 6 months before study start), unstable angina, heart failure ≥ NYHA functional classification system grade 2, severe cardiac arrhythmia requiring medication, metabolic dysfunction, severe renal disorder.
• •Any other malignancies than PDAC within the last 5 years before study start, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer
• •Hypersensitivity to the study drugs or to any of the excipients or to compounds with similar chemical or biologic composition
• •Use of strong CYP3A4 inhibitors (CYP3A4 inhibitors have to be discontinued at least one week prior to start of study treatment).
• •Use or strong UGT1A1 inhibitors or strong CYP3A4 inducers unless there are no therapeutic alternatives.
• •Known glucuronidation deficiency (Gilbert's syndrome) (specific screening not required)
• •Known DPD deficiency (specific screening not required)
• •Requirement for concomitant antiviral treatment with sorivudine or brivudine
• •Continuing abuse of alcohol, drugs, or medical drugs
• •Pregnant or breast-feeding females or FCBPs unable to either perform highly effective contraceptive measures or practice complete abstinence from heterosexual intercourse
• •Current or recent (within 4 weeks prior to randomization) treatment with an investigational drug or participation in an investigational clinical trial