The Scandinavian Randomized Controlled Trial of Isolated Hepatic Perfusion for Uveal Melanoma Liver Metastases

Study Overview
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Brief Summary
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A randomized controlled, open-label, multi-centre study evaluating if Isolated Hepatic Perfusion (IHP) increases Overall Survival compared with Best Alternative Care (BAC) in patients with isolated liver metastases from uveal melanoma.

Detailed Description
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Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumor, metastatic disease will ultimately develop in approximately 50% of the patients. 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. Isolated hepatic perfusion (IHP) is a regional treatment that was first performed more than 40 years ago (Aust and Ausman 1960). During IHP, the liver is completely isolated from the systemic circulation, allowing a high concentration of chemotherapy to be perfused through the liver with minimal systemic exposure. In a previous study from our institution, IHP was analysed based on improvements in the procedure and the results showed an improved outcome together with minimized morbidity and mortality over time. A phase II follow-up study confirms that IHP is a promising technique with tolerable morbidity. There are yet no randomized trials comparing overall survival in IHP, but in an attempt to answer this question the investigators did a register study showing a 14 months increased survival when comparing the patients treated with IHP with the longest surviving patients in Sweden during the same time period.

Official Title
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The Scandinavian Randomized Controlled Trial of Isolated Hepatic Perfusion for Uveal Melanoma Liver Metastases

Conditions
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Melanoma, Uveal Neoplasms

Intervention / Treatment
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* Procedure: IHP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged above 18 years. Signed and dated written informed consent before the start of specific protocol procedures. Histologically or cytologically proven liver metastases of uveal melanoma. If this is not possible at the time of randomization, a biopsy is mandatory before start of treatment. Liver metastases measurable by MRI (preferred) or CT of thorax and abdomen according to RECIST version 1.1 with at least one unidimensional measurable lesion ≥ 10 mm. The examination should be within 4 weeks prior to randomization. ECOG performance status of 0 or 1. No previous chemotherapy, radiotherapy, or biologic therapy for uveal melanoma metastases (ie first-line therapy) Adequate hepatic function (defined as ASAT,ALAT, bilirubin <= 3*ULN and PK-INR <= 1.5) and no medical history of liver cirrhosis or portal hypertension Exclusion Criteria: More than 50% of the liver volume (measured by CT or MRI) replaced by tumour. Evidence of extrahepatic disease by PET-CT Life expectancy of less than 4 months Pregnant or breast-feeding. Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study. Active infection. Ischemic cardiac disease or history of congestive heart failure with an LVEF < 40%. COPD or other chronic pulmonary disease with PFT's indicating an FEV< 50% predicted for age. Reduced renal function defined as S-Creatinine >=1.5xULN or Creatinine Clearance < 40 mL/min, calculated using the Cockroft and Gault formula. Reduced blood leukocytes or platelets defined as LPK < 2.0x109/L and TPK <100x109/L Use of live vaccines four weeks before or after the start of study. Body mass index above 35.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IHP<br>Isolated Hepatic Perfusion | Procedure: IHP<br> <br> |
| No Intervention: BAC<br>Best alternative care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | OS defined as the frequency of individuals alive at 24 months | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hepatic progression-free survival | Defined as time from randomization to progress of existing lesions, or appearance of new lesions, within the liver according to RECIST criteria (version 1.1) using CT or MRI. | 24 months | 
| Response | Defined as best response according to RECIST criteria (version 1.1) using CT or MRI. For the BAC-group, during the whole follow-up of 24 months. For the IHP-group, until hepatic progression (the time point when cross-over to the BAC-group is allowed). | 24 months | 
| Health economic evaluation | Health economic evaluation measured using QALY calculated using EQ5D-3L at all study visits. | 24 months | 
| SAE | Number of Participants with SAE as a Measure of Safety | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Perfusion Cancer Chemotherapy, Regional