PHP in Combination With IPI1/NIVO3 Compared to IPI3/NIVO1 Only in Patients With Uveal Melanoma Liver Metastases

NCT06519266 | Recruiting Phase 3 DMC FDA Drug FDA Device

• 1 other identifier: 2023-508156-20-00
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 6

Brief Summary

Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumor, 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. These metastases are generally refractory to systemic chemotherapy and the median survival for patients with liver metastases is about 6 months. Regardless of treatment, the mortality rate is approximately 90% at 2 years with only about 1% of the patients surviving more than 5 years. The primary objective with this study 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 include further efficacy and safety analysis, as well as biomarker discovery.

Conditions

Uveal Melanoma; Liver Metastases

Keywords

Percutaneous Hepatic Perfusion; Immunotherapy; Uveal Melanoma; Liver metastases; SCANDIUM III trial

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  The primary objective is to evaluate progression-free survival in patients with uveal melanoma hepatic dominant metastases randomized to either percutaneous hepatic perfusion (PHP) in combination with IPI1/NIVO3 or the combination of IPI3/NIVO1 only

  24 month

Secondary Outcomes (9)

• Adverse events

  24 month

• Overall response rate

  24 month

• Clinical benefit rate

  24 month

• Hepatic progression-free survival

  24 month

• Overall survival

  24 month

Other Outcomes (2)

• ctDNA zero-conversion rate at 24 weeks

  24 weeks

• Biomarker discovery

  24 month

Study Arms (2)

IPI3/NIVO1

ACTIVE COMPARATOR

Patients will be treated with 4 cycles of intravenous (i.v.) infusion with ipilimumab 3mg/kg and nivolumab 1mg/kg q3w followed by continued i.v. nivolumab 480mg q4w up to 1 year

Drug: IPI3/NIVO1

PHP + IPI1/NIVO3

EXPERIMENTAL

Patients will be treated with two cycles of PHP (CHEMOSAT® Hepatic Delivery System for Melphalan) six weeks apart, followed by two cycles of i.v. ipilimumab 1mg/kg and nivolumab 3mg/kg q3w, followed by continued i.v. nivolumab 480mg q4w up to 1 year

Device: PHP; Drug: IPI1/NIVO3

Interventions

PHP DEVICE

Patients will be treated with 2 cycles of PHP (CHEMOSAT® Hepatic Delivery System for Melphalan) six weeks apart

Also known as: CHEMOSAT® Hepatic Delivery System for Melphalan

PHP + IPI1/NIVO3

IPI1/NIVO3 DRUG

Patients will be treated with 2 cycles of i.v. ipilimumab 1mg/kg and nivolumab 3mg/kg q3w, followed by continued i.v. nivolumab 480mg q4w up to 1 year.

Also known as: Ipilimumab 1 mg/kg, Nivolumab 3 mg/kg

PHP + IPI1/NIVO3

IPI3/NIVO1 DRUG

Patients will be treated with 4 cycles of intravenous (i.v.) infusion with ipilimumab 3mg/kg and nivolumab 1mg/kg q3w followed by continued i.v. nivolumab 480mg q4w up to 1 year.

Also known as: Ipilimumab 3 mg/kg, Nivolumab 1 mg/kg

IPI3/NIVO1

Eligibility Criteria

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

You may qualify if:

• Patient is ≥18 years.
• Signed informed consent.
• ECOG performance status of 0 or 1.
• Histologically or cytologically confirmed liver metastasis of uveal melanoma.
• Measurable disease by computed tomography (CT) per RECIST 1.1 criteria with at least one target lesion identified in the liver.
• 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).
• Patient deemed suitable for percutaneous hepatic perfusion.
• 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 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.
• 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.

You may not qualify if:

• Life expectancy of less than 6 months.
• More than 50% of the liver volume replaced by tumor as measured by CT.
• Extrahepatic disease as measured by CT of thorax and abdomen.
• 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.
• History or evidence of clinically significant pulmonary disease e.g. severe COPD that precludes the use of general anesthesia.
• Patients who are unable to undergo general anesthesia for any reason.
• 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\>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.
• 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 reactions to monoclonal antibodies, melphalan, heparin or iodine contrast.
• Known human immunodeficiency virus (HIV) infection, acquired immunodeficiency syndrome (AIDS), hepatitis B or hepatitis C.
• Active autoimmune disease or a documented history of autoimmune disease requiring systemic immunomodulatory treatment. Diabetes, rheumatoid arthritis, psoriasis, atopic dermatitis and hypothyroidism are excepted.
• 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.

Sponsors & Collaborators

• Vastra Gotaland Region: lead

Study Sites (6)

Sahlgrenska University Hospital

Gothenburg, Sweden

RECRUITING

Linköping University Hospital

Linköping, Sweden

NOT YET RECRUITING

Skåne University Hospital

Lund, Sweden

NOT YET RECRUITING

Karolinska University Hospital,

Stockholm, Sweden

RECRUITING

Norrland University Hospital

Umeå, Sweden

NOT YET RECRUITING

Uppsala University Hospital

Uppsala, Sweden

RECRUITING

MeSH Terms

Conditions

Uveal Melanoma

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Roger Olofsson Bagge, Professor

  Sahlgrenska Universitetssjukhuset

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Roger Olofsson Bagge, Professor

CONTACT

+46313421000; roger.olofsson.bagge@vgregion.se

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2024
• First Posted: July 25, 2024
• Study Start: June 10, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: November 25, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

SE (6)