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A Study of Sorafenib in Patients With Chemonaive Metastatic Uveal Melanoma (STREAM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01377025
Recruitment Status : Unknown
Verified December 2014 by Prof. Dr. med. Max. E. Scheulen, University Hospital, Essen.
Recruitment status was:  Active, not recruiting
First Posted : June 20, 2011
Last Update Posted : December 3, 2014
ClinAssess GmbH
Information provided by (Responsible Party):
Prof. Dr. med. Max. E. Scheulen, University Hospital, Essen

Brief Summary:

Uveal melanoma is the most common primary intra-ocular malignancy in adults with an incidence of 0.6 - 0.7 per 100,000 per year.

Prognosis of metastatic uveal melanoma is poor. In retrospective analyses a median survival time after detection of metastases of 5 months (Flaherty et al, 1998) and 7 months (Kath et al, 1993) was reported. For patients receiving no treatment reported median survival was 2.0 months compared with 5.2 months for those receiving treatment for metastases (Gragoudas et al, 1991).

Up to now there is no established treatment of metastatic uveal melanoma. Some therapeutic approaches with locoregional treatment or systemic chemotherapy have been undertaken:

In case of metastatic disease which is confined to the liver in about 85% of patients with uveal melanoma surgical resection led to a median survival of 14 months (Mariani et al, 2009) or 19 months and a 5-year survival rate of 22% in a selected patient population (Adam et al, 2006).

As locoregional treatment option treatment with fotemustine via direct intra-arterial hepatic infusion was investigated and led to a median survival of 15 months (Peters et al, 2006). This was not a randomized trial, but a report on 101 consecutive treated patients. Additional debulking surgery was performed whenever feasible.

A randomized phase III trial comparing intra-arterial hepatic fotemustine administration with intravenous systemic fotemustine and overall survival as primary endpoint is still ongoing (EORTC 18021).

Thus, no systemic chemotherapy is approved for metastatic uveal melanoma. Although no specific genes have been linked to the pathogenesis of uveal melanoma, preclinical studies suggest potential benefit of inhibitors of Bcl-2, ubiquitin-proteasome, histone deactylase, mitogen-activated protein kinase and phosphatidylinositol-3-kinase-AKT pathways, and receptor tyrosine kinases.

Thus, sorafenib as inhibitor of b-Raf and Raf-1 (c-Raf or c-Raf-1), pro-angiogenic vascular endothelial growth factor receptor (VEGFR), and platelet-derived growth factor receptor (PDGFR) may potentially lead to a benefit for patients with metastatic uveal melanoma in terms of disease control and prolongation of survival.

Condition or disease Intervention/treatment Phase
Uveal Melanoma Drug: Placebo Drug: Sorafenib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Discontinuation, Blinded, Placebo-Controlled Phase II Study of Sorafenib in Patients With Chemonaive Metastatic Uveal Melanoma
Study Start Date : June 2011
Estimated Primary Completion Date : June 2016
Estimated Study Completion Date : June 2017

Arm Intervention/treatment
Experimental: Sorafenib blinded Phase
400 mg Sorafenib bid until PD
Drug: Sorafenib
400 mg Sorafenib bid until PD if staging after Run-In was SD

Placebo Comparator: Placebo blinded Phase
Two tbl. in the morning and two tbl. in teh evening until PD
Drug: Placebo
two tablets in the morning and two in the evening.

Experimental: Sorafenib Open Phase
400 mg Sorafenib bid until PD
Drug: Sorafenib
400 mg Sorafenib bid until PD if staging after Run-In was PR or CR

Primary Outcome Measures :
  1. Progression Free Survival [ Time Frame: Every 8 weeks for 1 year ]

Secondary Outcome Measures :
  1. Number of patients with adverse events [ Time Frame: Every 8 weeks for 1 year ]
  2. Overall Survival [ Time Frame: Every 8 weeks for 2 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  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, or 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
    • Alanine aminotransferase (ALT) ≤ 2.5 x ULN
    • Total bilirubin ≤ 3 mg/dl
    • Alkaline phosphatase ≤ 4.0 x ULN
  10. PT-INR/PT < 1.5 x ULN
  11. Females of childbearing potential (FCBP) must have a negative pregnancy test within 7 days of the first application of study treatment and must agree to use effective contraceptive birth control measures
  12. Males must agree to use barrier birth control measures (condoms) during the course of the trial.

Exclusion criteria:

  1. Previous or concurrent tumor other than uveal melanoma with the exception of cervical cancer in situ, adequately 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 ≥ 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. QT/QTc-interval prolongation (QTc> 450 msec) on ECG, known Long QT syndrome or known Long QT syndrome in relatives
  4. Known HIV infection
  5. Known chronic infection with hepatitis B or C
  6. Hypokalemia, hypocalcemia, hypomagnesemia or patients under actual treatment against hypokalemia, hypocalcemia, hypomagnesemia
  7. Active infection requiring systemic antibiotic/antiviral/antifungal treatment or any uncontrolled infection > Grade 2 NCI-CTCAE
  8. 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)
  9. Patients with seizure disorder requiring medication (such as steroids or antiepileptics)
  10. History of organ allograft
  11. Patients with evidence or history of bleeding diathesis
  12. Thrombotic or embolic events within the last 6 months
  13. Serious non-healing wound, ulcer or fracture
  14. 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
  15. Pregnant or breast-feeding patients
  16. Marked claustrophobia
  17. Cardiac pacemaker, cochlea implants or other implanted metal devices, residual metal splinters
  18. Known allergy to the used study drug sorafenib or to any of its excipients
  19. Known hypersensitivity to gadolinium based contrast agents
  20. Subject unwilling or unable to comply with study requirements
  21. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
  22. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01377025

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Universitätsmedizin Berlin, Charité Campus Benjamin Franklin
Berlin, Germany, 12203
Universitätsklinikum Erlangen
Erlangen, Germany, 91052
Univesitätsklinikum Essen
Essen, Germany, 45147
Sponsors and Collaborators
Prof. Dr. med. Max. E. Scheulen
ClinAssess GmbH
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Principal Investigator: Max E. Scheulen, Prof. Universiätsklinikum Essen
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Responsible Party: Prof. Dr. med. Max. E. Scheulen, Prof,. Dr. med., University Hospital, Essen Identifier: NCT01377025    
Other Study ID Numbers: STREAM
2010-022687-12 ( EudraCT Number )
First Posted: June 20, 2011    Key Record Dates
Last Update Posted: December 3, 2014
Last Verified: December 2014
Additional relevant MeSH terms:
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Uveal Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Uveal Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action