AzTrials
AzTrials

Uveal Melanoma, MetastaticPhase 1/2CHOPINNCT04283890

PHP and Immunotherapy in Metastasized UM

A Phase 1/2 study testing Ipilimumab and nivolumab and Melphalan chemosaturation via percutaneous hepatic perfusion in people with Uveal Melanoma, Metastatic, run by Leiden University Medical Center at 1 site in Netherlands.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

Melanoma of the eye (ocular/uveal melanoma) is an uncommon type of cancer that is associated with a high mortality. It usually disseminates rapidly throughout the body, most commonly to the liver and lungs. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Uveal Melanoma, Metastatic
What is being tested?
Ipilimumab and nivolumab and Melphalan chemosaturation via percutaneous hepatic perfusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
83 participants
Where
1 siteNetherlands
Study dates
4 Dec 2019to Dec 2029
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age between 18-75 yrs
  • World Health Organization (WHO) Performance Status 0 or I
  • 50% or less histologically or cytologically confirmed unresectable metastatic uveal melanoma in the parenchyma of the liver
  • Hepatic metastases, confined to or predominantly in the liver
  • No prior systemic treatment (including chemotherapy, vaccine therapy, monoclonal Ab treatment, IL-2)
  • Local pre-treatment of uveal melanoma metastases is allowed (resection and/or thermal ablation), except for chemotherapy containing procedures (e.g. chemoembolization) and radio-embolization, and as long as patients have progressed with measurable disease according to RECIST 1.1
Show all 13Show fewer
  • No concurrent systemic immunosuppressive medications ≥ 10mg/day prednisone or equivalent. Topical, inhaled, nasal and ophthalmic steroids, and adrenal replacement therapy are allowed.
  • Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Neutrophils ≥ 1.0x109/L, Platelets ≥ 100 x109/L, Hemoglobin ≥ 6.5 mmol/L, Creatinine ≤ 2x ULN, AST ≤ 2.5 x ULN, ALT ≤ 2.5 x ULN, Total bilirubin ≤ 1.5 X ULN, INR and PTT in normal range, LDH < 2xULN
  • Women of child bearing potential (WOCBP) must agree to use a reliable form of contraceptive as described in paragraph 5.4.
  • Men must agree to the use of male contraception as described in paragraph 5.4.
  • Absence of additional severe and/or uncontrolled concurrent disease
  • No prior, or ongoing other malignancy, except adequately treated basal cell or squamous cell skin cancer, cervical cancer in situ or adequately treated other cancer with eradicative intent for which the patient has been continuously disease-free for > 2 years.
  • No aberrant vascular anatomy of the liver that precludes PHP

Who cannot join

  • Cerebral or meningeal metastasized uveal melanoma
  • Subjects with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy;
  • Prior immunotherapy (tumor vaccine, cytokine, or growth factor)
  • Known history of infection with Human Immunodeficiency Virus;
  • Active infection requiring therapy, positive serology for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA)
  • History of congestive heart failure, active cardiac conditions, including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), significant arrhythmias and severe valvular disease must be evaluated for risks of undergoing general anesthesia.
Show all 16Show fewer
  • History or evidence of clinically significant pulmonary disease e.g. severe COPD that precludes the use of general anesthesia.
  • Underlying medical conditions that, in the Investigator's opinion, will make the administration of study treatment hazardous or obscure the interpretation of toxicity determination or adverse events;
  • Latex allergy, and known hypersensitivity/allergy to ipilimumab, nivolumab, melphalan or heparin
  • Prior Whipple's Surgery
  • Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids;
  • History of or current immunodeficiency disease, splenectomy or splenic irradiation; prior allogeneic stem cell transplantation;
  • Patients who are unable to be temporarily removed from chronic anti-coagulation therapy.
  • Patients with active bacterial infections with systemic manifestations (malaise, fever, leucocytosis) are not eligible until completion of appropriate therapy.
  • Use of other investigational drugs before study drug administration for systemic malignancy
  • Pregnancy or nursing

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Leiden University Medical Center

    Leiden, South Holland, 2333 ZA

Other trials in Netherlands

About this study

Official title: Phase1b/2 Study Combining Hepatic Percutaneous Perfusion With Ipilimumab Plus Nivolumab in Advanced Uveal Melanoma

Melanoma of the eye (ocular/uveal melanoma) is an uncommon type of cancer that is associated with a high mortality. It usually disseminates rapidly throughout the body, most commonly to the liver and lungs. In this study a combination therapy with immunotherapy (ipilimumab with nivolumab) and chemotherapy (melphalan) will be assessed for the treatment of disseminated uveal melanoma. Melphalan will be administered selectively to the liver via percutaneous hepatic perfusion, limiting the systemic effect of chemotherapy. With this treatment combination we aim to find a treatment for disseminated uveal melanoma, both in the liver as in the other organs.

Read the detailed description

Uveal melanoma (UM) is an uncommon malignancy (0.6-0.7 cases/100.000/year) that, in the case of metastatic stage, has a poor prognosis for response to treatment and survival. It is remarkable for its purely hematogenous pattern of dissemination, most commonly to the liver (60%) and lungs (25%). Current approaches using percutaneous hepatic perfusion (PHP) with melphalan resulted in response rates of up to 40% in the liver (1, 2) (for results of our own phase II study see paragraph 6.3.2). However, a main part of the patients developed extrahepatic disease in the follow-up, whereas the liver metastases were mainly stable.

Checkpoint inhibitors have been shown to improve overall survival in metastasized cutaneous melanoma in phase III studies (3-6), but seem to have limited activity as monotherapies in metastasized uveal melanoma (7-9). The combination of ipilimumab and nivolumab has achieved 2 out of 6 patients PR in a retrospective analysis (10). Interestingly, both patients had a liver-directed therapy (SIRT and chemoembolization) before the immunotherapy.

Combination of radio-frequency ablation (RFA) and anti-CTLA-4 enhanced antigen-loading of dendritic cells, and induced long-lasting anti-tumor immune responses in a murine melanoma model without induction of any severe side effects (11, 12). A phase Ib/II trial by Blank et al. (13) showed unconfirmed responses in some patients when RFA was combined with ipilimumab in uveal melanoma, but long-term disease stabilization was not achieved. Most of the responses were seen in extrahepatic metastases. Combining percutaneous hepatic perfusion (PHP) with checkpoint inhibitors could together lead to control of hepatic and extrahepatic disease. Therefore, we propose the current trial: Phase1b/2 Study Combining Hepatic Percutaneous Perfusion with Ipilimumab plus Nivolumab in advanced Uveal Melanoma (CHOPIN).

Being tested
Ipilimumab and nivolumab, Melphalan chemosaturation via percutaneous hepatic perfusion
Keywords
Advanced uveal melanoma, Percutaneous Hepatic Perfusion, Immunotherapy
Medical subject headings
Uveal Melanoma, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ipilimumab and nivolumabDrug

    The effect of ipilimumab and nivolumab has previously been tested in metastatic uveal melanoma. In this study the combination with percutaneous hepatic perfusion will be performed in order to evaluate the effect.

  • Melphalan chemosaturation via percutaneous hepatic perfusionDrug

    The effect of ipilimumab and nivolumab has previously been tested in metastatic uveal melanoma. In this study the combination with percutaneous hepatic perfusion will be performed in order to evaluate the effect.

Study groups in NCT04283890
Study groupRoleWhat they receive
Phase IbExperimentalNot described
Receives: Drug: Ipilimumab and nivolumab; Drug: Melphalan chemosaturation via percutaneous hepatic perfusion
Phase II - Combination treatmentActive comparatorNot described
Receives: Drug: Ipilimumab and nivolumab; Drug: Melphalan chemosaturation via percutaneous hepatic perfusion
Phase II - PHPActive comparatorNot described
Receives: Drug: Melphalan chemosaturation via percutaneous hepatic perfusion

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Toxicity and safety of treatment

    Dose limiting toxicities, maximum tolerated dose and recommended phase dose of the combination ipilimumab/nivolumab and PHP in patients with unresectable, histologically confirmed hepatic metastasis of uveal melanoma in phase Ib part.

    Measured: 36 weeks

  2. Efficacy and safety

    Description of PFS according to RECIST 1.1 at one year in the PHP group versus PHP + ipilimumab/nivolumab group in the phase II part.

    Measured: 1 year

Secondary outcomes (1)

  1. Response rate

    Description of response rate and overall survival, overall clinical response, and duration of response

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Feb 2020
  2. Study start4 Dec 2019
  3. Primary completionDec 2026 (estimated)
  4. Study completionDec 2029 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Model description
In the phase 1b part, safety and feasibility of combining percutaneous hepatic perfusion with 4 courses of ipilimumab and nivolumab will be investigated. In the randomized phase 2 part, efficacy as measured by progression-free survival at one year comparing PHP only versus PHP plus ipilimumab/nivolumab will be evaluated.
Masking
None (open label)
Enrolment
83 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04283890
Sponsor's protocol ID
NL69508.058.19
Acronym
CHOPIN
Status last verified
Sep 2025
First submitted
21 Feb 2020
Last updated
9 Sep 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • van den Hoek L, Burgmans M, Tong T, Goeman J, Speetjens F, Zunder S, van Erkel A, van der Meer R, van Rijswijk C, Lutjeboer J, Koolhaas D, Jonker-Bos M, Roozen I, Kropff S, van Meerten EVP, Zoethout R, Sitsen E, Helmerhorst H, Tijl F, Blank C, Kapiteijn E. Percutaneous hepatic perfusion combined with ipilimumab and nivolumab for metastatic uveal melanoma (CHOPIN): a single-centre, open-label, randomised, phase 2 trial. Lancet Oncol. 2026 Mar;27(3):372-382. doi: 10.1016/S1470-2045(25)00720-X.

    PubMed 41785896

  • Tong TML, van der Kooij MK, Speetjens FM, van Erkel AR, van der Meer RW, Lutjeboer J, van Persijn van Meerten EL, Martini CH, Zoethout RWM, Tijl FGJ, Blank CU, Burgmans MC, Kapiteijn E. Combining Hepatic Percutaneous Perfusion with Ipilimumab plus Nivolumab in advanced uveal melanoma (CHOPIN): study protocol for a phase Ib/randomized phase II trial. Trials. 2022 Feb 13;23(1):137. doi: 10.1186/s13063-022-06036-y.

    PubMed 35152908

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Ipilimumab and nivolumab and Melphalan chemosaturation via percutaneous hepatic perfusion in people with Uveal Melanoma, Metastatic, run by Leiden University Medical Center at 1 site in Netherlands.

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 13 inclusion and 16 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: under way, not looking for participants, as of the sponsor's last update on 9 Sep 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 Netherlands. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Toxicity and safety of treatment (time frame: 36 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04283890, which also lists 2 linked publications.

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 9 Sep 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in