Clinical trial NCT01785316: The Scandinavian Randomized Controlled Trial of Isolated Hepatic Perfusion for Uveal Melanoma Liver Metastases
Official title: The Scandinavian Randomized Controlled Trial of Isolated Hepatic Perfusion for Uveal Melanoma Liver Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Melanoma
Uveal Neoplasms
Keywords: Perfusion Cancer Chemotherapy, Regional
Lead sponsor: Vastra Gotaland Region
Sponsor class: OTHER_GOV
Collaborators: name: Karolinska University Hospital
name: University Hospital, Linkoeping
name: Uppsala University Hospital
name: Skane University Hospital
name: University Hospital, Umeå
name: Rigshospitalet, Denmark
First posted: 2013-02-07
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Male or female aged above 18 years.
2. Signed and dated written informed consent before the start of specific protocol procedures.
3. 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.
4. 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.
5. ECOG performance status of 0 or 1.
6. No previous chemotherapy, radiotherapy, or biologic therapy for uveal melanoma metastases (ie first-line therapy)
7. 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:

1. More than 50% of the liver volume (measured by CT or MRI) replaced by tumour.
2. Evidence of extrahepatic disease by PET-CT
3. Life expectancy of less than 4 months
4. Pregnant or breast-feeding. Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study.
5. Active infection.
6. Ischemic cardiac disease or history of congestive heart failure with an LVEF \< 40%.
7. COPD or other chronic pulmonary disease with PFT's indicating an FEV\< 50% predicted for age.
8. Reduced renal function defined as S-Creatinine \>=1.5xULN or Creatinine Clearance \< 40 mL/min, calculated using the Cockroft and Gault formula.
9. Reduced blood leukocytes or platelets defined as LPK \< 2.0x109/L and TPK \<100x109/L
10. Use of live vaccines four weeks before or after the start of study.
11. Body mass index above 35.

Primary outcomes:
measure: Overall survival
timeFrame: 24 months
Secondary outcomes:
measure: Hepatic progression-free survival
timeFrame: 24 months
measure: Response
timeFrame: 24 months
measure: Health economic evaluation
timeFrame: 24 months
measure: SAE
timeFrame: 24 months
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
Study officials:
affiliation: Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
name: Roger Olofsson Bagge, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rizell M, Mattson J, Cahlin C, Hafstrom 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.
citation: Olofsson R, Cahlin C, All-Ericsson C, Hashimi F, Mattsson J, Rizell M, Lindner 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.
citation: Olofsson Bagge R, Nelson A, Shafazand A, All-Eriksson C, Cahlin C, Elander N, Helgadottir H, Kiilgaard JF, Kinhult S, Ljuslinder I, Mattsson J, Rizell M, Sternby Eilard M, Ullenhag GJ, Nilsson JA, Ny L, Lindner P. Isolated Hepatic Perfusion With Melphalan for Patients With Isolated Uveal Melanoma Liver Metastases: A Multicenter, Randomized, Open-Label, Phase III Trial (the SCANDIUM Trial). J Clin Oncol. 2023 Jun 1;41(16):3042-3050. doi: 10.1200/JCO.22.01705. Epub 2023 Mar 20.
citation: Olofsson R, Ny L, Eilard MS, Rizell M, Cahlin C, Stierner U, Lonn U, Hansson J, Ljuslinder I, Lundgren L, Ullenhag G, Kiilgaard JF, Nilsson J, Lindner P. Isolated hepatic perfusion as a treatment for uveal melanoma liver metastases (the SCANDIUM trial): study protocol for a randomized controlled trial. Trials. 2014 Aug 9;15:317. doi: 10.1186/1745-6215-15-317.