choroid melanoma MedDRA version: 16.1 Level: PT Classification code 10008773 Term: Choroid melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Universitätsklinikum Essen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed and dated written informed consent before the start of specific protocol procedures 2. Metastatic uveal melanoma with histological or cytological confirmation of liver metastasis (histological or cytological confirmation in case of only extrahepatic metastasis not required for inclusion) 3. By means of whole-body MRI documented disease according to RECIST version 1.1 with at least one unidimensional measurable lesion = 10 mm 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 5. Male or female patients = 18 years of age 6. Estimated life-expectancy more than 5 months 7. Hematologic function, as follows: Absolute neutrophil count (ANC) = 1.5 x 109/L Platelet count = 100 x 109/L Hemoglobin = 9 g/dL 8. Renal function, as follows Creatinine = 1.5 x upper limit of normal (ULN) 9. Hepatic function, as follows Aspartate aminotransferase (AST) = 2.5 x ULN (if liver metastases = 5 x ULN) Alanine aminotransferase (ALT) = 2.5 x ULN (if liver metastases = 5 x ULN) Total bilirubin = 3 mg/dl Alkaline phosphatase = 4.0 x ULN 10. PT-INR/PT =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Previous or concurrent tumor other than uveal melanoma with the exception of cervical cancer in situ, adaequately treated basal cell carcinoma, superficial bladder tumors (Ta, Tis, and T1) or any curatively treated tumors > 3 years prior to enrollment 2. History of cardiac disease: congestive heart failure = New York Heart Association (NYHA) class 2; active coronary artery disease ([CAD], myocardial infarction more than 6 months prior to study entry is allowed), cardiac arrhythmias requiring antiarrhythmic therapy (only beta blockers or digoxin are permitted) 3. Known HIV infection 4. Known chronic infection with hepatitis B or C 5. Active infection requiring systemic antibiotic/antiviral/antifungal treatment or any uncontrolled infection > Grade 2 NCI-CTCAE 6. Symptomatic brain or meningeal tumors (unless patient is > 6 months from definitive therapy, had a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study enrollment) 7. Patients with seizure disorder requiring medication (such as steroids or antiepileptics) 8. History of organ allograft 9. Patients with evidence or history of bleeding diathesis 10. Thrombotic or embolic events within the last 6 months 11. Serious non-healing wound, ulcer or fracture 12. Uncontrolled arterial hypertension with systolic blood pressure >150 mm Hg and/ or diastolic blood pressure > 90 mg Hg despite optimal treatment, determined twice within one week 13. Pregnant or breast-feeding patients 14. Marked claustrophobia 15. Cardiac pacemaker, cochlea implants or other implanted metal devices, residual metal splinters 16. Known allergy to the used study drug sorafenib or to any of its excipients 17. Known hypersensitivity to gadolinium based contrast agents 18. Subject unwilling or unable to comply with study requirements 19. Substance abuse, medical, psychological or social conditions that may interfere with the patient´s participation in the study or evaluation of the study results 20. Participation in any clinical study or treatment with an experimental drug or experimental therapy within 28 days prior to study enrollment or during study participation 21. Patients receiving anticoagulation therapy with warfarin or phenprocoumon 22. Treatment with any of the following therapies or drugs - Any prior palliative chemotherapy, tyrosine kinase inhibitors (TKI´s) or antiangiogenics (prior adjuvant treatment with vaccine or immunotherapy is allowed provided there is documentation of disease progression). - Any chemotherapy, hormonal therapy, immunotherapy, targeted therapy or experimental or approved proteins/antibodies within four weeks prior to study enrollment or during study participation. - Radiotherapy or brachytherapy within four weeks prior to study enrollment or during study participation except to eye or bone. - Hepatic chemoembolization within four weeks prior to study enrollment or during study participation: - Major surgery within 4 weeks of study enrollment - Autologous bone marrow transplant or stem cell rescue within 4 months of study enrollment - Use of biologic response modifiers, such as G-CSF, within 3 week of study enrollment. (G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator; however, they may not be substituted for a required dose reduction.) - Patie
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine progression free survival (PFS) of sorafenib versus placebo after random assignment (randomized subset only).;Primary end point(s): PFS under treatment with sorafenib versus treatment with placebo after random assignment to blinded study medication in the randomized subset (tumor assessment according to RECIST version 1.1 criteria);Secondary Objective: To compare safety and tolerability in randomization phase The following secondary objectives refer to all patients enrolled: - To determine median overall survival - To determine disease control rate (DCR) - To determine overall PFS and time to progression (TTP) - To determine response rate - To determine whether tumor markers correlate with clinical benefit and whether tumor markers in run-in phase predict clinical benefit - To determine PFS and TTP after unblinding and retreatment with sorafenib (only in subjects randomized to placebo and retreated with sorafenib) - Safety and tolerability | — |
Countries
Germany
Outcome results
None listed