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Assessment of the effects of an oral chemotherapy (Regorafenib) after failure of previous treatments for non-operable patients suffering from a particular type of biliary tract cancer.

Phase 1
Conditions
ocally advanced (non resectable) and metastatic histologically proven intra-hepatic or hilum cholangiocarcinoma + histologically proven metastatic extra-hepatic cholangiocarcinoma (common bile duct and gallbladder), progressing after gemcitabine-CDDP (or gemcitabine-oxaliplatin) or after gemcitabine alone followed or preceded by platinum-based chemotherapy
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2012-005626-30-BE
Lead Sponsor
CUB Erasme Hospital
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
66
Inclusion Criteria

- histologically proven locally advanced unresectable or metastatic intra-hepatic or hilum cholangiocarcinoma or histologically proven metastatic extra-hepatic cholangiocarcinoma (common bile duct and gallbladder)
- progression documented after GEM-CDDP (or GEM-OX), or gemcitabine alone followed or preceded by platinum-based chemotherapy
- signed written informed consent
- Male or female = 18 years of age
- 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 requirements conducted 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) = 3.0x ULN (<5x ULN for patients with liver involvement of their cancer).
oAmylase and lipase =1.5x ULN.
oAlkaline phosphatase (ALP) = 2.5x ULN (=5x ULN for patients with liver involvement of their cancer and /or have bone metastases)
oPlatelets count =100.000/mm³, hemoglobin (Hb) =9 g/dL, absolute neutrophil count (ANC) =1500/mm³
oInternation normalized ratio (INR) =1.5x ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) = 1.5 x ULN unless receiving treatment with therapeutic anticoagulation. Patients being treated with anticoagulant, e.g. heparin, will be allowed to participate provided no prior evidence of an underlying abnormality in these parameters exists. Close monitoring of at least weekly evaluations will be performed until INR and PTT are stable based on a pre-dose measurement as defined by the local standard of care.
- life expectancy of at least 12 weeks
- effective contraception for both male and female patients must be used for at least 8 weeks after the last study drug administration if the risk of conception exists
- negative pregnancy test, only applicable if there is a risk of conception
- negative proteinuria on dipstick or 24 hours proteinuria<1000mg

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 44
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 22

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)
- persistent proteinuria >3.5g/24 hours measured by urine protein-creatinine ratio from a random urine sample (persistent proteinuria >3 non-healing woud, ulcer, or bone fracture
- patients with evidence or history of any bleeding diathesis, irrespective of severity
- any hemorrhage or bleeding event = CTCAE Grade 3 within 4 weeks prior to the start of study medication
- interstitial lung disease with ongoing signs and symptoms at the time of informed consent
- uncontrolled concurrent CNS, cardiac, infectious diseases, hypertension
- history of myocardial infarction (6 months before start of study drug)
- arterial or venous thrombotic events such as cerebrovascular accident (CVA) (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study medication (except for adequately treated catheter-related venous thrombosis occurring more than one month before the start of study medication)
- uncontrolled cardiac arrhythmias
- 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)
- pheochomocytoma
- HIV infection
- active chronic hepatitis B or C with a need for antiviral treatment
- 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 > grade 2 NCI CTCAE
- 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

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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