A Study of Sorafenib in Patients With Chemonaive Metastatic Uveal Melanoma

NCT01377025 | Unknown Phase 2

• 2 other identifiers: STREAM2010-022687-12
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 3

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.

Conditions

Uveal Melanoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Every 8 weeks for 1 year

Secondary Outcomes (2)

• Number of patients with adverse events

  Every 8 weeks for 1 year

• Overall Survival

  Every 8 weeks for 2 years

Study Arms (3)

Sorafenib blinded Phase

EXPERIMENTAL

400 mg Sorafenib bid until PD

Drug: Sorafenib

Placebo blinded Phase

PLACEBO COMPARATOR

Two tbl. in the morning and two tbl. in teh evening until PD

Drug: Placebo

Sorafenib Open Phase

EXPERIMENTAL

400 mg Sorafenib bid until PD

Drug: Sorafenib

Interventions

Placebo DRUG

two tablets in the morning and two in the evening.

Placebo blinded Phase

Sorafenib DRUG

400 mg Sorafenib bid until PD if staging after Run-In was PR or CR

Sorafenib Open Phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated written informed consent before the start of specific protocol procedures
• Metastatic uveal melanoma with histological or cytological confirmation of liver metastasis
• By means of whole body MRI documented disease according to RECIST version 1.1 with at least one unidimensional measurable lesion ≥ 10 mm
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Male or female patients ≥ 18 years of age
• Estimated life-expectancy more than 5 months
• Hematologic function, as follows:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Hemoglobin ≥ 9 g/dL
• Renal function, as follows
• Creatinine ≤ 1.5 x upper limit of normal (ULN)
• Hepatic function, as follows
• Aspartate aminotransferase (AST) ≤ 2.5 x ULN
• Alanine aminotransferase (ALT) ≤ 2.5 x ULN

You may not qualify if:

• 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
• 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)
• QT/QTc-interval prolongation (QTc\> 450 msec) on ECG, known Long QT syndrome or known Long QT syndrome in relatives
• Known HIV infection
• Known chronic infection with hepatitis B or C
• Hypokalemia, hypocalcemia, hypomagnesemia or patients under actual treatment against hypokalemia, hypocalcemia, hypomagnesemia
• Active infection requiring systemic antibiotic/antiviral/antifungal treatment or any uncontrolled infection \> Grade 2 NCI-CTCAE
• 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)
• Patients with seizure disorder requiring medication (such as steroids or antiepileptics)
• History of organ allograft
• Patients with evidence or history of bleeding diathesis
• Thrombotic or embolic events within the last 6 months
• Serious non-healing wound, ulcer or fracture
• 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
• Pregnant or breast-feeding patients

Sponsors & Collaborators

• Prof. Dr. med. Max. E. Scheulen: lead
• ClinAssess GmbH: collaborator

Study Sites (3)

Universitätsmedizin Berlin, Charité Campus Benjamin Franklin

Berlin, 12203, Germany

Location

Universitätsklinikum Erlangen

Erlangen, 91052, Germany

Location

Univesitätsklinikum Essen

Essen, 45147, Germany

Location

Related Publications (1)

• Kalkavan H, Scheulen ME, Kampgen E, Keilholz U, Heinzerling L, Lueong SS, Hlinka A, Gromke T, Ochsenreither S, Hilger RA, Grubert M, Wetter A, Guberina N, Zeschnigk M, Ferency P, Held S, Hinke A, Schuler G, Al-Ghazzawi K, Bornfeld N, Bechrakis NE, Schuler M, Bauer S, Richly H, Siveke JT. Sorafenib as first-line therapy for metastatic uveal melanoma: A multicenter, placebo-controlled randomized discontinuation study (STREAM). iScience. 2025 Nov 14;28(12):114045. doi: 10.1016/j.isci.2025.114045. eCollection 2025 Dec 19.

  PMID: 41362626 DERIVED

MeSH Terms

Conditions

Uveal Melanoma

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Max E. Scheulen, Prof.

  Universiätsklinikum Essen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof,. Dr. med.

Study Record Dates

• First Submitted: June 14, 2011
• First Posted: June 20, 2011
• Study Start: June 1, 2011
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2017
• Last Updated: December 3, 2014

Record last verified: 2014-12

Locations

DE (3)