- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01893099
Sorafenib and Radioembolization With Sir-Spheres® for the Treatment of Metastatic Ocular Melanoma
April 19, 2018 updated by: Prof Olivier Michielin, M.D., Ph.D., Centre Hospitalier Universitaire Vaudois
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Primary objective:
To evaluate the safety and tolerability of sorafenib in combination with SIR-Spheres® radioembolization in uveal melanoma patients metastatic to the liver.
Secondary objectives:
- Translational research on biomarkers (blood and liver biopsies) as well as on radiological exam by using microbubble contrast enhanced ultrasound. Angiogenic markers such as VEGF, IGF-2, TFG Angiopoietin-2 and IL-8 will be monitored. Correlations will be investigated between the angiogenic markers (blood & tumor tissue), angiogenic radiological exam and the response to the treatment.
- To evaluate the response, clinical benefit, PFS and survival of the patients.
Study Type
Interventional
Enrollment (Actual)
11
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Lausanne, Switzerland
- Centre Hospitalier Universitaire Vaudois
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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
- Alkaline phosphatase < 4 x ULN
- PT-INR/PTT < 1.5 x ULN
- Serum creatinine ≤ 1.5 x ULN
- Signed and dated informed consent before the start of specific protocol procedures
Exclusion Criteria:
- 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
- Autologous bone marrow transplant or stem cell rescue within 4 months of study treatment.
- Use of biologic response modifiers, such as G-CSF, within 3 weeks of study treatment.
- Investigational drug therapy outside of this trial during or within 4 weeks of study treatment
- Prior exposure to the study drug
- Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Sorafenib- Cohort 1
Sorafenib 400 mg BID will be started 14 days after the administration of SIRT with SIR-Sphere®.
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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.
Other Names:
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Experimental: Sorafenib- Cohort 2
Sorafenib 400 mg BID will be started 11 days after the administration of SIRT with SIR-Sphere®.
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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.
Other Names:
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Experimental: Sorafenib- Cohort 3
Sorafenib 400 mg BID will be started 3 days after the administration of radioembolization with SIR-Sphere®.
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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.
Other Names:
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Experimental: Sorafenib- Cohort 4
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.
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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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Toxicity
Time Frame: 30 days of treatment of sorafenib
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Toxicities will be assessed according to the NCI-CTCAE (version 4.0).
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30 days of treatment of sorafenib
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival (OS)
Time Frame: 2 years
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2 years
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Progression-free survival (PFS)
Time Frame: 2 years
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2 years
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Translational research on biomarkers
Time Frame: 2 years
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Measurement of angiogenic factors and evaluation of angiogenesis with dynamic micro-bubble contrast-enhanced US
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2 years
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Clinical benefit
Time Frame: 2 years
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Clinical benefit (CR, PR and NC) evaluated with 18F-FDG-PET CT scan and CT scan by using respectively PERCIST criteria and RECIST criteria
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2 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Olivier Michielin, MD, Centre Hospitalier Universitaire Vaudois
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2013
Primary Completion (Actual)
November 28, 2017
Study Completion (Actual)
November 28, 2017
Study Registration Dates
First Submitted
July 2, 2013
First Submitted That Met QC Criteria
July 2, 2013
First Posted (Estimate)
July 8, 2013
Study Record Updates
Last Update Posted (Actual)
April 23, 2018
Last Update Submitted That Met QC Criteria
April 19, 2018
Last Verified
April 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CHUV-CePO-code 16295
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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