Uveal MelanomaPhase 1SCANDIUM IINCT04463368
Isolated Hepatic Perfusion in Combination With Ipilimumab and Nivolumab in Patients With Uveal Melanoma Metastases
A Phase 1 study testing Isolated hepatic perfusion, Ipilimumab and Nivolumab in people with Uveal Melanoma and Liver Metastases, run by Vastra Gotaland Region at 1 site in Sweden.
Trial summary
Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumour, metastatic disease will develop in approximately 35%-50% of the patients within 10 years. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Uveal Melanoma, Liver Metastases
- What is being tested?
- Isolated hepatic perfusion, Ipilimumab and Nivolumab
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteSweden
- Study dates
- 8 Mar 2021to 26 Jul 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient is ≥18 years of age on the day of signing informed consent
- Patient is willing and able to provide written informed consent and comply with study procedures. Written informed consent must be signed and dated before the start of specific protocol procedures
- Patient must have a histologically confirmed diagnosis of stage IV uveal melanoma. If tissue biopsy is judged not feasible by the investigator, cytological diagnosis from fine needle aspiration (FNA) will be accepted
- Measurable disease by computed tomography (CT) or Magnetic Resonance Imaging (MRI) per RECIST 1.1 criteria with at least one target lesion identified in the liver.
- ECOG performance status of 0 or 1
- No previous immunotherapy for uveal melanoma metastases.
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- Female patient of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Female patients of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
- Male patients of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
Who cannot join
- Life expectancy of less than 3 months
- Body mass index above 35
- More than 50% of the liver volume replaced by tumor as measured by CT or MRI
- Known congestive heart failure with an LVEF <40%
- COPD or other chronic pulmonary disease with PFT's indicating an FEV< 50% predicted for age
- Interstitial lung disease (ILD) or (non-infectious) pneumonitis
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- Reduced renal function defined as S-Creatinine >=1.5xULN or Creatinine Clearance < 40 mL/min, calculated using the Cockroft and Gault formula
- Reduced hepatic function (defined as AST, ALT, bilirubin>3*ULN and PK-INR>1.5) or medical history of liver cirrhosis or portal hypertension
- Hemoglobin <90 g/L or platelets <100x109/L or neutrophils <1.5x109/L
- Use of live vaccines four weeks before or after the last study treatment
- History of severe hypersensitivity reactions to mAbs
- Known human immunodeficiency virus (HIV) infection, acquired immunodeficiency syndrome (AIDS), hepatitis B or hepatitis C
- Active autoimmune disease or a history of known or suspected autoimmune disease
- A condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- Concomitant therapy with any other anti-cancer therapy, concurrent medical conditions requiring use of immunosuppressive medications or use of other investigational drugs
- Has a known additional malignancy that is progressing or requires active treatment.
- Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study drug.
- A history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator
Trial locations and contacts
1 site in 1 country.
About this study
Official title: SCANDIUM II Trial - A Phase I Randomized Controlled Multicentre Trial of Isolated Hepatic Perfusion in Combination With Ipilimumab and Nivolumab in Patients With Uveal Melanoma Metastases
Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumour, metastatic disease will develop in approximately 35%-50% of the patients within 10 years. The liver is the most common site for metastases, and about 50% of the patients will have isolated liver metastases. Isolated hepatic perfusion is a regional treatment where the liver is completely isolated from the systemic circulation, allowing a high concentration of chemotherapy to be perfused through the liver with minimal systemic exposure. The introduction of modern immunotherapy in the treatment arsenal for cutaneous melanoma also creates hope for patients with uveal melanoma metastases. However, the results of immunotherapy have so far been disappointing. The reason for the low efficacy could be that uveal melanoma develops in the immune privileged eye.
The hypothesis in this trial is that isolated hepatic perfusion with melphalan causes an immunogenic type of cell death by local tumour destruction while leaving the immune-system intact. This will cause an activation of the immune-system and the addition of ipilimumab and nivolumab will enhance this effect, ultimately increasing the treatment efficacy.
Read more
The primary objective of this trial is to evaluate the safety and tolerability of isolated hepatic perfusion together with ipilimumab and nivolumab when given at the same time or as a sequenced regimen. The study design is a phase I randomized controlled, multicentre, open-label trial. Active follow-up will be performed for 2 years. Patients will be randomized after diagnoses of metastatic disease to one of the following treatment arms:
Arm A. Patients will be treated with IHP followed by 4 courses of ipilimumab 3mg/kg and nivolumab 1mg/kg every third week followed by continued nivolumab 480mg q4w up to 1 year.
Arm B. Patients will be treated with 1 course of ipilimumab 3mg/kg and nivolumab 1mg/kg followed by IHP after 3 weeks and then another 3 courses of ipilimumab 3mg/kg and nivolumab 1mg/kg every third week followed by continued nivolumab 480mg q4w up to 1 year.
- Conditions
- Uveal Melanoma, Liver Metastases
- Being tested
- Isolated hepatic perfusion, Ipilimumab, Nivolumab
- Medical subject headings
- Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isolated hepatic perfusionProcedure or surgery
The procedure is performed under general anaesthesia. The caval vein is isolated infrahepatically above the renal veins and suprahepatically between the diaphragm and the pericardium. A catheter is placed in the retrohepatic portion of the caval vein for perfusion outflow. The portal vein is clamped and the proper hepatic artery is cannulated via the gastroduodenal artery. The liver perfusion is performed at a rate of 8- 9 ml/kg/min with a target liver temperature of 40 degrees Celsius. The leakage from the system was continuously recorded using Technetium labelled albumin (Vasculosis) injected into the perfusion circuit. Melphalan (1 mg/kg bodyweight divided into two doses, given 30 minutes apart) is added to the perfusion system. The perfusion is then continued for 60 minutes, after which the perfusion was discontinued.
IpilimumabDrug
4 courses of ipilimumab 3mg/kg every third week
NivolumabDrug
4 courses of nivolumab 1mg/kg every third week
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Patients will be treated with IHP followed by 4 courses of ipilimumab 3mg/kg and nivolumab 1mg/kg every third week followed by continued nivolumab 480mg q4w up to 1 year. Receives: Procedure: Isolated hepatic perfusion; Drug: Ipilimumab; Drug: Nivolumab |
| Arm B | Experimental | Patients will be treated with 1 course of ipilimumab 3mg/kg and nivolumab 1mg/kg followed by IHP after 3 weeks and then another 3 courses of ipilimumab 3mg/kg and nivolumab 1mg/kg every third week followed by continued nivolumab 480mg q4w up to 1 year. Receives: Procedure: Isolated hepatic perfusion; Drug: Ipilimumab; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
Measured: 1 year
Secondary outcomes (7)
Objective response rate (ORR)
Evaluation of objective response rate (ORR)
Measured: 2 years
Clinical benefit rate (CBR)
Evaluation of clinical benefit rate (CBR)
Measured: 2 years
Progression-free survival (PFS)
Evaluation of progression-free survival (PFS)
Measured: 2 years
Hepatic progression-free survival (hPFS)
Evaluation of hepatic progression-free survival (hPFS)
Measured: 2 years
Overall survival (OS)
Evaluation of overall survival (OS)
Measured: 2 years
Time to response (TTR)
Evaluation of time to response (TTR)
Measured: 2 years
Duration of response (DOR)
Evaluation of duration of response (DOR)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2020
- Study start8 Mar 2021
- Primary completion26 Jul 2024
- Study completion26 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Uveal MelanomaStudies of the same condition, open and under way.
- More trials run by Vastra Gotaland RegionThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vastra Gotaland Region
- Sponsor type
- Other government
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Principal investigator, Roger Olofsson Bagge, Sahlgrenska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04463368
- Sponsor's protocol ID
- CA184-587
- Acronym
- SCANDIUM II
- Status last verified
- Mar 2025
- First submitted
- 5 Jul 2020
- Last updated
- 28 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SCANDIUM II Trial - A Phase I Randomized Controlled Multicentre Trial of Isolated Hepatic Perfusion in Combination With Ipilimumab and Nivolumab in Patients With Uveal Melanoma Metastases
- ClinicalTrials.gov ID
- NCT04463368
- Acronym / sponsor ID
- SCANDIUM II / CA184-587
- Conditions
- Uveal Melanoma, Liver Metastases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Vastra Gotaland RegionOther government
- Collaborators
- Bristol-Myers Squibb
- Study start
- 8 Mar 2021 (actual)
- Primary completion
- 26 Jul 2024 (actual)
- Study completion
- 26 Jul 2024 (actual)
- First posted
- 9 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumour, metastatic disease will develop in approximately 35%-50% of the patients within 10 years. The liver is the most common site for metastases, and about 50% of the patients will have isolated liver metastases. Isolated hepatic perfusion is a regional treatment where the liver is completely isolated from the systemic circulation, allowing a high concentration of chemotherapy to be perfused through the liver with minimal systemic exposure. The introduction of modern immunotherapy in the treatment arsenal for cutaneous melanoma also creates hope for patients with uveal melanoma metastases. However, the results of immunotherapy have so far been disappointing. The reason for the low efficacy could be that uveal melanoma develops in the immune privileged eye.
The hypothesis in this trial is that isolated hepatic perfusion with melphalan causes an immunogenic type of cell death by local tumour destruction while leaving the immune-system intact. This will cause an activation of the immune-system and the addition of ipilimumab and nivolumab will enhance this effect, ultimately increasing the treatment efficacy.
The primary objective of this trial is to evaluate the safety and tolerability of isolated hepatic perfusion together with ipilimumab and nivolumab when given at the same time or as a sequenced regimen. The study design is a phase I randomized controlled, multicentre, open-label trial. Active follow-up will be performed for 2 years. Patients will be randomized after diagnoses of metastatic disease to one of the following treatment arms:
Arm A. Patients will be treated with IHP followed by 4 courses of ipilimumab 3mg/kg and nivolumab 1mg/kg every third week followed by continued nivolumab 480mg q4w up to 1 year.
Arm B. Patients will be treated with 1 course of ipilimumab 3mg/kg and nivolumab 1mg/kg followed by IHP after 3 weeks and then another 3 courses of ipilimumab 3mg/kg and nivolumab 1mg/kg every third week followed by continued nivolumab 480mg q4w up to 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Procedure: Isolated hepatic perfusion, Drug: Ipilimumab, Drug: NivolumabPatients will be treated with IHP followed by 4 courses of ipilimumab 3mg/kg and nivolumab 1mg/kg every third week followed by continued nivolumab 480mg q4w up to 1 year. |
| Arm B | Experimental | Procedure: Isolated hepatic perfusion, Drug: Ipilimumab, Drug: NivolumabPatients will be treated with 1 course of ipilimumab 3mg/kg and nivolumab 1mg/kg followed by IHP after 3 weeks and then another 3 courses of ipilimumab 3mg/kg and nivolumab 1mg/kg every third week followed by continued nivolumab 480mg q4w up to 1 year. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patient is ≥18 years of age on the day of signing informed consent
- Patient is willing and able to provide written informed consent and comply with study procedures. Written informed consent must be signed and dated before the start of specific protocol procedures
- Patient must have a histologically confirmed diagnosis of stage IV uveal melanoma. If tissue biopsy is judged not feasible by the investigator, cytological diagnosis from fine needle aspiration (FNA) will be accepted
- Measurable disease by computed tomography (CT) or Magnetic Resonance Imaging (MRI) per RECIST 1.1 criteria with at least one target lesion identified in the liver.
- ECOG performance status of 0 or 1
Key exclusion criteria (18 listed)
- Life expectancy of less than 3 months
- Body mass index above 35
- More than 50% of the liver volume replaced by tumor as measured by CT or MRI
- Known congestive heart failure with an LVEF <40%
- COPD or other chronic pulmonary disease with PFT's indicating an FEV< 50% predicted for age
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Isolated hepatic perfusionThe procedure is performed under general anaesthesia. The caval vein is isolated infrahepatically above the renal veins and suprahepatically between the diaphragm and the pericardium. A catheter is placed in the retrohepatic portion of the caval vein for perfusion outflow. The portal vein is clamped and the proper hepatic artery is cannulated via the gastroduodenal artery. The liver perfusion is performed at a rate of 8- 9 ml/kg/min with a target liver temperature of 40 degrees Celsius. The leakage from the system was continuously recorded using Technetium labelled albumin (Vasculosis) injected into the perfusion circuit. Melphalan (1 mg/kg bodyweight divided into two doses, given 30 minutes apart) is added to the perfusion system. The perfusion is then continued for 60 minutes, after which the perfusion was discontinued. | Procedure or surgery | Arm A, Arm B |
| Ipilimumab4 courses of ipilimumab 3mg/kg every third week | Drug | Arm A, Arm B |
| Nivolumab4 courses of nivolumab 1mg/kg every third week | Drug | Arm A, Arm B |
Primary outcome
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
Time frame: 1 year
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
7 secondary outcomes
Objective response rate (ORR)
Time frame: 2 years
Clinical benefit rate (CBR)
Time frame: 2 years
Progression-free survival (PFS)
Time frame: 2 years
Hepatic progression-free survival (hPFS)
Time frame: 2 years
Overall survival (OS)
Time frame: 2 years
Time to response (TTR)
Time frame: 2 years
Duration of response (DOR)
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Isolated hepatic perfusion, Ipilimumab and Nivolumab in people with Uveal Melanoma and Liver Metastases, run by Vastra Gotaland Region at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2025.