SCANDIUM: The Scandinavian Randomized Controlled Trial of Isolated Hepatic Perfusion for Uveal Melanoma Liver Metastases
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: IHP Isolated Hepatic Perfusion |
Procedure: IHP
|
| No Intervention: BAC Best alternative care |
Outcome Measures
Primary Outcome Measures
- Overall survival [24 months]
OS defined as the frequency of individuals alive at 24 months
Secondary Outcome Measures
- Hepatic progression-free survival [24 months]
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.
- Response [24 months]
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).
- Health economic evaluation [24 months]
Health economic evaluation measured using QALY calculated using EQ5D-3L at all study visits.
- SAE [24 months]
Number of Participants with SAE as a Measure of Safety
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female aged above 18 years.
-
Signed and dated written informed consent before the start of specific protocol procedures.
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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.
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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.
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ECOG performance status of 0 or 1.
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No previous chemotherapy, radiotherapy, or biologic therapy for uveal melanoma metastases (ie first-line therapy)
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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:
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More than 50% of the liver volume (measured by CT or MRI) replaced by tumour.
-
Evidence of extrahepatic disease by PET-CT
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Life expectancy of less than 4 months
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Pregnant or breast-feeding. Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study.
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Active infection.
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Ischemic cardiac disease or history of congestive heart failure with an LVEF < 40%.
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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.
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Reduced blood leukocytes or platelets defined as LPK < 2.0x109/L and TPK <100x109/L
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Use of live vaccines four weeks before or after the start of study.
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Body mass index above 35.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sahlgrenska University Hospital | Gothenburg | Sweden | 413 45 |
Sponsors and Collaborators
- Sahlgrenska University Hospital, Sweden
- Karolinska University Hospital
- University Hospital, Linkoeping
- Uppsala University Hospital
- Skane University Hospital
- University Hospital, Umeå
- Rigshospitalet, Denmark
Investigators
- Principal Investigator: Roger Olofsson Bagge, Dr, Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Olofsson R, Cahlin C, All-Ericsson C, Hashimi F, Mattsson J, Rizell M, Lindnér P. Isolated hepatic perfusion for ocular melanoma metastasis: registry data suggests a survival benefit. Ann Surg Oncol. 2014 Feb;21(2):466-72. doi: 10.1245/s10434-013-3304-z. Epub 2013 Oct 19.
- Rizell M, Mattson J, Cahlin C, Hafström L, Lindner P, Olausson M. Isolated hepatic perfusion for liver metastases of malignant melanoma. Melanoma Res. 2008 Apr;18(2):120-6. doi: 10.1097/CMR.0b013e3282f8e3c9.
- SUGBG-013001