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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
11

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Switzerland
      • Lausanne, Switzerland
        • Centre hospitalier universitaire vaudois

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Sorafenib- Cohort 1
Sorafenib 400 mg BID will be started 14 days after the administration of SIRT with SIR-Sphere®.
Drug: Sorafenib
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:
  • Nexavar®
Device: Radioembolization with SIR-Spheres® (Yttrium Microspheres)
Experimental: Sorafenib- Cohort 2
Sorafenib 400 mg BID will be started 11 days after the administration of SIRT with SIR-Sphere®.
Drug: Sorafenib
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:
  • Nexavar®
Device: Radioembolization with SIR-Spheres® (Yttrium Microspheres)
Experimental: Sorafenib- Cohort 3
Sorafenib 400 mg BID will be started 3 days after the administration of radioembolization with SIR-Sphere®.
Drug: Sorafenib
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:
  • Nexavar®
Device: Radioembolization with SIR-Spheres® (Yttrium Microspheres)
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.
Drug: Sorafenib
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:
  • Nexavar®
Device: Radioembolization with SIR-Spheres® (Yttrium Microspheres)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Toxicity
Time Frame: 30 days of treatment of sorafenib
Toxicities will be assessed according to the NCI-CTCAE (version 4.0).
30 days of treatment of sorafenib

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: 2 years
2 years
Progression-free survival (PFS)
Time Frame: 2 years
2 years
Translational research on biomarkers
Time Frame: 2 years
Measurement of angiogenic factors and evaluation of angiogenesis with dynamic micro-bubble contrast-enhanced US
2 years
Clinical benefit
Time Frame: 2 years
Clinical benefit (CR, PR and NC) evaluated with 18F-FDG-PET CT scan and CT scan by using respectively PERCIST criteria and RECIST criteria
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Centre Hospitalier Universitaire Vaudois

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 28, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 28, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 2, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 2, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 8, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 23, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 19, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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