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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2011 by University Hospital, Essen
Sponsor:
Information provided by:
University Hospital, Essen
ClinicalTrials.gov Identifier:
NCT01377025
First received: June 14, 2011
Last updated: June 22, 2011
Last verified: April 2011
  Purpose

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 Intervention Phase
Uveal Melanoma
Drug: Placebo
Drug: Sorafenib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by University Hospital, Essen:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: Every 8 weeks for 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of patients with adverse events [ Time Frame: Every 8 weeks for 1 year ] [ Designated as safety issue: Yes ]
  • Overall Survival [ Time Frame: Every 8 weeks for 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: June 2011
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01377025

Contacts
Contact: Max El Scheulen, Prof. +49201723 ext 3152 max.scheulen@uk-essen.de

Locations
Germany
Universitätsmedizin Berlin, Charité Campus Benjamin Franklin Not yet recruiting
Berlin, Germany, 12203
Contact: Ulrich Keilholz, Prof.Dr.med.    +30450513502    ulrich.keilholz@charite.de   
Principal Investigator: Ulrich Keilholz, Prof.Dr.med.         
Sub-Investigator: Ronny Schuster, Dr. med.         
Sub-Investigator: Verena Kümmerlen, Dr. med.         
Sub-Investigator: Konrad Klinghammer, Dr. med.         
Sub-Investigator: Anne Letsch, Dr. med.         
Universitätsklinikum Erlangen Not yet recruiting
Erlangen, Germany, 91052
Contact: Eckhart Kämpgen, Prof.Dr.med.    +499131853 ext 3661    eckhart.kaempgen@uk-erlangen.de   
Principal Investigator: Eckhart Kämpgen, Prof.Dr.med.         
Sub-Investigator: Michael Erdmann, Dr. med.         
Sub-Investigator: Lisa Löhberg, Dr. med.         
Sub-Investigator: Kerstin L. Gebhard-Schmauser, Dr. med.         
Sub-Investigator: Cornelia Erfurt-Berge, Dr. med.         
Sub-Investigator: Petra Keikavoussi, Dr. med.         
Univesitätsklinikum Essen Recruiting
Essen, Germany, 45147
Contact: Max. E. Scheulen, Prof.Dr.med.    +49201723 ext 3152    max.scheulen@uk-essen.de   
Principal Investigator: Max E. Scheulen, Prof.Dr.med.         
Sub-Investigator: Heike Richly, Dr. med.         
Sub-Investigator: Andreas C. Hoffmann, Dr. med.         
Sponsors and Collaborators
University Hospital, Essen
Investigators
Principal Investigator: Max E. Scheulen, Prof. Universiätsklinikum Essen
  More Information

No publications provided

Responsible Party: Prof. Dr. med. Max E. Scheulen, Universitätsklinikum Essen
ClinicalTrials.gov Identifier: NCT01377025     History of Changes
Other Study ID Numbers: STREAM, 2010-022687-12
Study First Received: June 14, 2011
Last Updated: June 22, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Melanoma
Uveal Neoplasms
Eye Diseases
Eye Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Uveal Diseases
Sorafenib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014