PHP and Immunotherapy in Metastasized UM

NCT04283890 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: NL69508.058.19
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Uveal Melanoma, Metastatic

Keywords

Advanced uveal melanoma; Percutaneous Hepatic Perfusion; Immunotherapy

Outcome Measures

Primary Outcomes (2)

• 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.

  36 weeks

• 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.

  1 year

Secondary Outcomes (1)

• Response rate

  1 year

Study Arms (3)

Phase Ib

EXPERIMENTAL

Drug: Ipilimumab and nivolumab; Drug: Melphalan chemosaturation via percutaneous hepatic perfusion

Phase II - Combination treatment

ACTIVE COMPARATOR

Drug: Ipilimumab and nivolumab; Drug: Melphalan chemosaturation via percutaneous hepatic perfusion

Phase II - PHP

ACTIVE COMPARATOR

Drug: Melphalan chemosaturation via percutaneous hepatic perfusion

Interventions

Ipilimumab and nivolumab DRUG

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.

Phase II - Combination treatment; Phase Ib

Melphalan chemosaturation via percutaneous hepatic perfusion DRUG

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.

Phase II - Combination treatment; Phase II - PHP; Phase Ib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18-75 yrs
• World Health Organization (WHO) Performance Status 0 or I
• % 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
• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (1)

Leiden University Medical Center

Leiden, South Holland, 2333 ZA, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 35152908 DERIVED

MeSH Terms

Conditions

Uveal Melanoma; Neoplasm Metastasis

Interventions

Ipilimumab; Nivolumab

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ellen W. Kapiteijn, MD, PhD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open label, single center, phase Ib/randomized phase II trial, evaluating the safety and efficacy (as measured by RECIST 1.1) of the combination of PHP and ipilimumab/nivolumab in patients with unresectable hepatic and extrahepatic metastases of uveal melanoma.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Model Details: 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.

Study Record Dates

• First Submitted: February 21, 2020
• First Posted: February 25, 2020
• Study Start: December 4, 2019
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2029
• Last Updated: September 9, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)