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

ConditionsUveal Melanoma Liver Metastases

Trial statusRecruiting

Trial phasePhase 3

Trial typeInterventional

Biological sexAll

Age18+

SponsorVastra Gotaland Region

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patient is ≥18 years.

Signed informed consent.

ECOG performance status of 0 or 1.

Histologically or cytologically confirmed liver metastasis of uveal melanoma.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

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

Treatment groups

40 Participants

are divided into 2 treatment groups

Group A: IPI3/NIVO1Active comparator 1 intervention

Group B: PHP + IPI1/NIVO3Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

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

Time frame

24 month

Secondary outcomes

Adverse events

Frequency and severity of AEs and SAEs graded according to the NCI CTCAE v5.0.

Time frame

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

Time frame

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

Time frame

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.

Time frame

24 month

Other outcomes

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

Time frame

24 weeks

Biomarker discovery

Predictive and prognostic biomarker discovery

Time frame

24 month

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Vastra Gotaland Region

Lead sponsor

Source ClinicalTrials.gov

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