Sorafenib and Radioembolization With Sir-Spheres® for the Treatment of Metastatic Ocular Melanoma

NCT01893099 | Completed Phase 1

• 1 other identifier: CHUV-CePO-code 16295
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

The best way to combine a loco-regional procedure such as chemoembolisation or radioembolization combined with an anti-angiogenic drug is not clear. This phase I trial aims to establish, first, the tolerability of the combination of liver radioembolization with SirSpheres® and sorafenib in uveal melanoma patients with liver metastasis studying different schedules of administration of sorafenib after and before radioembolization. Secondly, we aim to evaluate angiogenic markers modifications during these different schedules, either in the serum or radiologicaly. Dose of Sorafenib will be 400 mg BID and the timing of introduction will differ for one cohort to the other, given after the radioembolization for initials cohorts and finally, before and concomitantly to radioembolization for the last cohort.

Conditions

Ocular Melanoma

Outcome Measures

Primary Outcomes (1)

• Toxicity

  Toxicities will be assessed according to the NCI-CTCAE (version 4.0).

  30 days of treatment of sorafenib

Secondary Outcomes (4)

• Translational research on biomarkers

  2 years

• Clinical benefit

  2 years

• Progression-free survival (PFS)

  2 years

• Overall survival (OS)

  2 years

Study Arms (4)

Sorafenib- Cohort 1

EXPERIMENTAL

Sorafenib 400 mg BID will be started 14 days after the administration of SIRT with SIR-Sphere®.

Drug: Sorafenib; Device: Radioembolization with SIR-Spheres® (Yttrium Microspheres)

Sorafenib- Cohort 2

EXPERIMENTAL

Sorafenib 400 mg BID will be started 11 days after the administration of SIRT with SIR-Sphere®.

Drug: Sorafenib; Device: Radioembolization with SIR-Spheres® (Yttrium Microspheres)

Sorafenib- Cohort 3

EXPERIMENTAL

Sorafenib 400 mg BID will be started 3 days after the administration of radioembolization with SIR-Sphere®.

Drug: Sorafenib; Device: Radioembolization with SIR-Spheres® (Yttrium Microspheres)

Sorafenib- Cohort 4

EXPERIMENTAL

Sorafenib 400 mg BID will be started 7 days prior to the administration of radioembolization with SIR-Spheres® and be given continuously, without drug holidays.

Drug: Sorafenib; Device: Radioembolization with SIR-Spheres® (Yttrium Microspheres)

Interventions

Sorafenib DRUG

Sorafenib will be given at the dosage of 400 mg BID. Initiation of the drug will vary dependently of the cohort and will be continued until progressive disease or intolerance.

Also known as: Nexavar®

Sorafenib- Cohort 1; Sorafenib- Cohort 2; Sorafenib- Cohort 3; Sorafenib- Cohort 4

Radioembolization with SIR-Spheres® (Yttrium Microspheres) DEVICE

Sorafenib- Cohort 1; Sorafenib- Cohort 2; Sorafenib- Cohort 3; Sorafenib- Cohort 4

Eligibility Criteria

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

You may qualify if:

• Metastatic uveal melanoma with proven histology (stage IV)
• Presence of liver metastases
• Concomitant non life-threatening metastases outside the liver are allowed
• Palliative radiotherapy will be allowed outside the liver
• Previous chemotherapy or immunotherapy at least 4 weeks before study treatment is allowed
• Age ≥ 18 years
• ECOG Performance Status of 0 or 1
• Life expectancy of at least 12 weeks
• Subjects with at least one uni-dimensional (by RECIST) measurable lesion. Lesions must be measured by CT-scan or MRI
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to study treatment
• Hemoglobin ≥ 9.0 g/dl
• Absolute neutrophil count (ANC) ≥ 1,500/mm3
• Platelet count ≥ 100,000/ul
• Total bilirubin ≤ 1.5 times the upper limit of normal (ULN)
• ALT and AST ≤ 5 x ULN

You may not qualify if:

• History of cardiac disease: congestive heart failure \>NYHA class 2; active coronary artery disease (myocardial infarction more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension.
• History of HIV infection or chronic hepatitis B or C.
• Active clinically serious infections (\> grade 2 NCI-CTC version 4.0).
• Symptomatic metastatic brain or meningeal tumors (unless the patient is \> 6 months from definitive therapy, has a negative imaging study within 4 weeks before treatment start and is clinically stable with respect to the tumor at the time of study treatment).
• Patients with seizure disorder requiring medication (such as steroids or anti-epileptics).
• History of organ allograft.
• Patients with evidence or history of bleeding diasthesis.
• Patients undergoing renal dialysis.
• Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumor (Ta, Tis and T1) or any cancer curatively treated \> 3 years prior to study treatment.
• Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test 72h before all investigations related to the protocol. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and two weeks after the completion of trial (and men for at least 3 months after last administration of study medication).
• Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study.
• Patients unable to swallow oral medications.
• Pre-treatment with any antiangiogenic agents (Bevacizumab, Sunitinib, or other TKI inhibitors affecting the vessels)
• Radiotherapy on the liver
• Major surgery within 4 weeks of start of treatment

Sponsors & Collaborators

• Centre Hospitalier Universitaire Vaudois: lead

Study Sites (1)

Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland

Location

Related Publications (1)

• Berthod G, Cisarovsky C, Petrova T, Decosterd LA, Choong E, Celestini D, Cuendet MA, Boughdad S, Prior JO, Meuwly JY, Figg WD, Michielin O, Leyvraz S. Sorafenib plus selective internal radiotherapy with 90Y resin microspheres for the treatment of uveal melanoma with liver metastasis: a phase I trial. Br J Cancer. 2025 Dec 11. doi: 10.1038/s41416-025-03279-9. Online ahead of print.

  PMID: 41381843 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

• Olivier Michielin, MD

  Centre Hospitalier Universitaire Vaudois

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior physician

Study Record Dates

• First Submitted: July 2, 2013
• First Posted: July 8, 2013
• Study Start: June 1, 2013
• Primary Completion: November 28, 2017
• Study Completion: November 28, 2017
• Last Updated: April 23, 2018

Record last verified: 2018-04

Locations

CH (1)