Regorafenib Versus Placebo to Treat Cholangiocarcinoma (REACHIN)

This is an interventional treatment trial for Cholangiocarcinoma focused on measuring Intra-hepatic, Hilar, Locally Advanced, Non Resectable, Metastatic, Regorafenib, Placebo Read More

Inclusion Criteria:

• histologically proven intra-hepatic or hilum cholangiocarcinoma (mass forming, not "liniting" tumor), locally advanced unresectable or metastatic
• progression documented after GEM-CDDP (or GEM-OX), or gemcitabine alone followed or preceded by platinum-based (CDDP or oxaliplatin) chemotherapy
• age > 18 years
• ECOG PS 0/1 at study entry
• measurable disease according to RECIST version 1.1
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirementsconducted within 7 days of starting to study treatment:

oSerum creatinine <1.5x upper reference range

oTotal bilirubin <1.5x ULN

oAlanine transaminase (ALT) and aspartate aminotransferase (AST) < 2.5x ULN (<5x ULN forpatients with liver involvement of their cancer).

oAmylase and lipase <1.5x ULN.

• life expectancy of at least 12 weeks
• effective contraception for both male and female patients if the risk of conception exists
• negative proteinuria on dipstick or 24 hours proteinuria<1000mg
• signed written informed consent

Exclusion Criteria:

• unability to take oral medication
• any malabsorption condition
• patients taking strong cytochrome P (CYP) CYP3A4 inhibitors (eg. Clarithromycin, indinavir,itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin,voriconazole) or strong CYP3A4 inducers (eg. Carbamazepine, phenobarbital, phenytoin, rifampin, St-John's Wort) (see section 8)
• persistent proteinuria >3.5g/24 hours measured by urine protein-creatinine ratio from a random urinesample (persistent proteinuria >3 non-healing woud, ulcer, or bone fracture
• any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of studymedication
• interstitial lund disease with ongoing signs and symptoms at the time of informed consent
• uncontrolled concurrent CNS, cardiac, infectious diseases, hypertension
• history of myocardial infarction, deep venous or arterial thrombosis, cerebrovascular accident (CVA) during the last 6 months
• previous exposure to anti-VEGF targeting therapy (including Regorafenib) and to signal transduction inhibitors
• known hypersensitivity to any of the components of study treatments
• previous malignancy in the last past 5 years except basal cell cancer of the skin or preinvasive cancer of the cervix
• pregnant or lactating women, or patients of both genders with procreative potential not using adequate contraceptive methods
• medical or psychological conditions that would not permit the patient to complete the study or sign inform consent
• unstable angina, congestive heart failure ≥NYHA class II
• uncontrolled hypertension despite optimal management (systolic blood pressure >150 mmHg or diastolic pressure > 90mmHg)
• pheochromocytoma
• HIV infection
• active chronic hepatitis B or C with a need for antiviral treatment
• liver failure, cirrhosis Chil Pugh B or C
• brain metastasis
• major surgery, open biopsy or significant traumatic injury within 4 weeks prior to the first dose of treatment
• intra-hepatic locoregional therapy (DC Beads, SIRT)
• history of organ allograft
• ongoing infection
• renal failure requiring dialysis
• patients receiving or having received any investigational treatment within 4 weeks prior to study entry, or participating to another clinical study