A Phase III Randomized Controlled Multicentre Trial of Percutaneous Hepatic Perfusion in Combination with Ipilimumab and Nivolumab Compared to Ipilimumab and Nivolumab Only in Patients with Uveal Melanoma Liver Metastases – the SCANDIUM III trial.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vaestra Goetalandsregionen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Diseases [C] - Neoplasms [C04]

Trial duration

10 Jun 2024 → ongoing

Decision date (initial)

2026-03-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

The primary objective is to evaluate progression-free survival in patients with uveal melanoma liver metastases randomized to either percutaneous hepatic perfusion (PHP) in combination with ipilimumab and nivolumab or ipilimumab and nivolumab only.

Secondary objectives 1

1. Study the efficacy and safety, as well as perform biomarker discovery analysis.

Conditions and MedDRA coding

Uveal Melanoma Liver Metastases

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Patient is ≥18 years.
2. Signed informed consent.
3. ECOG performance status of 0 or 1.
4. Histologically or cytologically confirmed liver metastasis of uveal melanoma.
5. Measurable disease by computed tomography (CT) per RECIST 1.1 criteria with at least one target lesion identified in the liver.
6. No previous treatment for uveal melanoma metastases, except patients that have confirmed progression on tebentafusp, or after surgical resection or ablative treatments (e.g., radiofrequency ablation or stereotactic body radiation therapy).
7. Patient deemed suitable for percutaneous hepatic perfusion.
8. 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.
9. Female patients of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 150 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
10. Male patients of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 150 days after the last dose of study therapy. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Exclusion criteria 18

1. Life expectancy of less than 6 months.
2. More than 50% of the liver volume replaced by tumor as measured by CT.
3. Extrahepatic disease as measured by CT of thorax and abdomen.
4. 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 that precludes the use of general anesthesia.
5. History or evidence of clinically significant pulmonary disease e.g. severe COPD that precludes the use of general anesthesia.
6. Patients who are unable to undergo general anesthesia for any reason.
7. Reduced renal function defined as S-Creatinine >=1.5xULN or Creatinine Clearance < 40 mL/min, calculated using the Cockroft and Gault formula.
8. Reduced hepatic function (defined as AST, ALT, bilirubin>2.5*ULN and PK-INR>1.5) or medical history of liver cirrhosis (Child-Pugh Class B or C) or evidence of portal hypertension by history, endoscopy or radiology.
9. Hemoglobin <90 g/L or platelets <100x109/L or neutrophils <1.5x109/L
10. Use of live vaccines four weeks before or after the last study treatment.
11. History of severe reactions to monoclonal antibodies, melphalan, heparin or iodine contrast.
12. Known human immunodeficiency virus (HIV) infection, acquired immunodeficiency syndrome (AIDS), hepatitis B or hepatitis C.
13. Active autoimmune disease or a documented history of autoimmune disease requiring systemic immunomodulatory treatment. Diabetes, rematoid arthritis, psoriasis, atopic dermatitis and hypothyroidism are excepted.
14. 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.
15. Concomitant therapy with any other anti-cancer therapy, concurrent medical conditions requiring use of immunosuppressive medications or use of other investigational drugs.
16. Has a known additional malignancy that is progressing or requires active treatment.
17. Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 150 days after the last dose of study drug.
18. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS)

Secondary endpoints 11

1. Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
2. Objective response rate (ORR)
3. Clinical benefit rate (CBR)
4. Hepatic progression-free survival (hPFS)
5. Extrahepatic progression-free survival (xhPFS)
6. Overall survival (OS)
7. Melanoma-specific survival (MSS)
8. Duration of response (DOR)
9. Quality of Life (QoL)
10. ctDNA zero-conversion rate at 24 weeks
11. Predictive and prognostic biomarker discovery

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vaestra Goetalandsregionen

Sponsor organisation

Vaestra Goetalandsregionen

Address

Regionens Hus

City

Vänersborg

Postcode

462 80

Country

Sweden

Scientific contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Roger Olofsson Bagge

Public contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Roger Olofsson Bagge

Locations

2 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 17 files

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

Application history

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