PHP in Combination With IPI1/NIVO3 Compared to IPI3/NIVO1 Only in Patients With Uveal Melanoma Liver Metastases
NCT Number: NCT06519266
Acronym: SCANDIUM-III
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Uveal Melanoma|Liver Metastases
Interventions: DEVICE: PHP|DRUG: IPI1/NIVO3|DRUG: IPI3/NIVO1
Sponsor: Vastra Gotaland Region
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 40
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-01
Completion Date: 2030-12-31
Locations: Sahlgrenska University Hospital, Gothenburg, Sweden|Linköping University Hospital, Linköping, Sweden|Skåne University Hospital, Lund, Sweden|Karolinska University Hospital,, Stockholm, Sweden|Norrland University Hospital, Umeå, Sweden|Uppsala University Hospital, Uppsala, Sweden

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.

Primary Outcome Measures: 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 Outcome Measures: Adverse events, Frequency and severity of AEs and SAEs graded according to the NCI CTCAE v5.0., 24 month|Overall response rate, Evaluation of objective response rate (ORR), defined as the percentage of patients achieving a confirmed complete or partial response, as defined by RECIST version 1.1 criteria, 24 month|Clinical benefit rate, Evaluation of clinical benefit rate (CBR), defined as the percentage of patients achieving confirmed SD or any confirmed CR or PR. As defined by RECIST version 1.1 criteria, 24 month|Hepatic progression-free survival, Evaluation of hepatic PFS (hPFS), defined as the time-to-event defined by the first documented disease progression in the liver or death due to any cause, whichever occurs first, from randomization. hPFS will be determined based on tumor assessment using RECIST version 1.1 criteria., 24 month|Overall survival, Evaluation of overall survival (OS), defined as the time from randomization to death from any cause., 24 month|Melanoma-specific survival, Evaluation of melanoma-specific survival (MSS), defined as the time from randomization to death from uveal melanoma, 24 month|Duration of response, Evaluation of duration of response (DOR), defined as the time to first documented progression or death due to underlying cancer from the first document CR or PR, 24 month|Quality of Life as assessed by FACT-G, Evaluation of QoL using The Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire, where overall scores for FACT-G and the sub scales physical (PWB), social (SWB), emotional (EWB), and functional well-being (FWB) will be reported., 24 month|Quality of Life as assessed by EQ-5D-5L, Evaluation of QoL using EQ-5D-5L where EQ-VAS (0-100) will be reported, 24 month
Other Outcome Measures: ctDNA zero-conversion rate at 24 weeks, ctDNA zero-conversion rate at 24 weeks, defined as the percentage of patients that at 24 weeks have no measurable ctDNA levels compared to baseline sample, 24 weeks|Biomarker discovery, Predictive and prognostic biomarker discovery, 24 month