Chopin

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Leids Universitair Medisch Centrum (LUMC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]

Decision date (initial)

2024-09-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-516127-14-01

EudraCT number

2018-004248-49

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To determine safety and tolerability, dose limiting toxicities (DLTs), maximum tolerated dose
(MTD) and recommended phase II dose (RPTD) of the combination of ipilimumab plus
nivolumab and PHP in patients with unresectable, histologically confirmed metastases of
uveal melanoma will be evaluated in the phase Ib part of the study.
The efficacy of PHP alone versus the combination of PHP with ipilimumab/nivolumab will be determined in the randomized phase II study.

Secondary objectives 1

1. - To evaluate best overall response rate according to RECIST 1.1 and iRECIST of patients treated with PHP alone versus patientswith the combination of PHP with ipilimumab and nivolumab. - To evaluate overall survival of patients treated with PHP alone versus patients with the combination of PHP with ipilimumab andnivolumab.

Conditions and MedDRA coding

metastasized melonama uveal

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Age between 18-80 years World Health Organization (WHO) Performance Status 0 or I 50% or less histologically or cytologically confirmed unresectable metastatic uveal melanoma in the parenchymaof 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 forchemotherapy containing procedures (e.g. chemoembolization) and radio-embolization, and as long as patientshave 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 ≤ 1.5 x ULN, LDH <2xULN Women of child bearing potential (WOCBP) must agree to use a reliable form of contraceptive as described in theresearch protocol Men must agree to the use of male contraception as described in the research protocol 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, cervicalcancer in situ or adequately treated other cancer with eradicative intent for which the patient has beencontinuously disease-free for >2 years. No aberrant vascular anatomy of the liver that precludes PHP

Exclusion criteria 1

1. Cerebral or meningeal metastasized uveal melanoma; Subjects with any active autoimmune disease or a documented history of autoimmune disease, or history ofsyndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo orresolved 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 and/or Hepatitis C ribonucleicacid (RNA); History of congestive heart failure, active cardiac conditions, including unstable coronary syndromes (unstable orsevere angina, recent myocardial infarction), significant arrhythmias and severe valvular disease must beevaluated for risks of undergoing general anesthesia; History or evidence of clinically significant pulmonary disease e.g. severe COPD that precludes the use of generalanesthesia; Underlying medical conditions that, in the Investigator's opinion, will make the administration of study treatmenthazardous 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 celltransplantation; 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 eligibleuntil completion of appropriate therapy; Use of other investigational drugs before study drug administration for systemic malignancy; Pregnancy or nursing

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Safety and feasibility of combining percutaneous hepatic perfusion with ipilimumab and nivolumab (phase 1b part).
2. Efficacy as measured by progression-free survival at one year comparing PHP alone versus patients with the combination of PHP with ipilimumab and nivolumab (randomized phase 2 part).

Secondary endpoints 2

1. To evaluate best overall response rate according to RECIST 1.1 and iRECIST of patients treated with PHP alone versus patients with the combination of PHP with ipilimumab and nivolumab.
2. To evaluate overall survival of patients treated with PHP alone versus patients with the combination of PHP with ipilimumab and nivolumab.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Leids Universitair Medisch Centrum (LUMC)

Sponsor organisation

Leids Universitair Medisch Centrum (LUMC)

Address

Albinusdreef 2

City

Leiden

Postcode

2333 ZA

Country

Netherlands

Scientific contact point

Organisation

Leids Universitair Medisch Centrum (LUMC)

Contact name

H.W. Kapiteijn

Public contact point

Organisation

Leids Universitair Medisch Centrum (LUMC)

Contact name

H.W. Kapiteijn

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications