Top

Published in:

Open Access 01-12-2014 | Study protocol

Isolated hepatic perfusion as a treatment for uveal melanoma liver metastases (the SCANDIUM trial): study protocol for a randomized controlled trial

Authors: Roger Olofsson, Lars Ny, Malin Sternby Eilard, Magnus Rizell, Christian Cahlin, Ulrika Stierner, Ulf Lönn, Johan Hansson, Ingrid Ljuslinder, Lotta Lundgren, Gustav Ullenhag, Jens Folke Kiilgaard, Jonas Nilsson, Per Lindnér

Published in: Trials | Issue 1/2014

Abstract

Background

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 patients, with the liver being the most common site for metastases. The median survival for patients with liver metastases is between 6 and 12 months, and no treatment has in randomized trials ever been shown to prolong survival. A previous phase II trial using isolated hepatic perfusion (IHP) has suggested a 14-month increase in overall survival compared with a historic control group consisting of the longest surviving patients in Sweden during the same time period (26 versus 12 months).

Methods/Design

This is the protocol for a multicenter phase III trial randomizing patients with isolated liver metastases of uveal melanoma to IHP or best alternative care (BAC). Inclusion criteria include liver metastases (verified by biopsy) and no evidence of extra-hepatic tumor manifestations by positron emission tomography–computed tomography (PET-CT). The primary endpoint is overall survival at 24 months, with secondary endpoints including response rate, progression-free survival, and quality of life. The planned sample size is 78 patients throughout five years.

Discussion

Patients with isolated liver metastases of uveal melanoma origin have a short expected survival and no standard treatment option exists. This is the first randomized clinical trial to evaluate IHP as a treatment option with overall survival being the primary endpoint.

Trial registration

ClinicalTrials.gov registration number: NCT01785316 (registered 1 February 2013). EudraCT registration number: 2013-000564-29.

Diener-West M, Earle JD, Fine SL, Hawkins BS, Moy CS, Reynolds SM, Schachat AP, Straatsma BR: The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, III: initial mortality findings. COMS Report No. 18. Arch Ophthalmol. 2001, 119: 969-982.CrossRefPubMed

Kujala E, Makitie T, Kivela T: Very long-term prognosis of patients with malignant uveal melanoma. Invest Ophthalmol Vis Sci. 2003, 44: 4651-4659. 10.1167/iovs.03-0538.CrossRefPubMed

Bedikian AY, Papadopoulos N, Plager C, Eton O, Ring S: Phase II evaluation of temozolomide in metastatic choroidal melanoma. Melanoma Res. 2003, 13: 303-306. 10.1097/00008390-200306000-00013.CrossRefPubMed

Schmittel A, Scheulen ME, Bechrakis NE, Strumberg D, Baumgart J, Bornfeld N, Foerster MH, Thiel E, Keilholz U: Phase II trial of cisplatin, gemcitabine and treosulfan in patients with metastatic uveal melanoma. Melanoma Res. 2005, 15: 205-207. 10.1097/00008390-200506000-00010.CrossRefPubMed

Kivela T, Suciu S, Hansson J, Kruit WH, Vuoristo MS, Kloke O, Gore M, Hahka-Kemppinen M, Parvinen LM, Kumpulainen E, Humblet Y, Pyrhonen S: Bleomycin, vincristine, lomustine and dacarbazine (BOLD) in combination with recombinant interferon alpha-2b for metastatic uveal melanoma. Eur J Cancer. 2003, 39: 1115-1120. 10.1016/S0959-8049(03)00132-1.CrossRefPubMed

Carvajal RD, Sosman JA, Quevedo F: Phase II study of selumetinib (sel) versus temozolomide (TMZ) in gnaq/Gna11 (Gq/11) mutant (mut) uveal melanoma (UM). J Clin Oncol. 2013, Suppl 15: CRA9003-

Danielli R, Ridolfi R, Chiarion-Sileni V, Queirolo P, Testori A, Plummer R, Boitano M, Calabro L, Rossi CD, Giacomo AM, Ferrucci PF, Ridolfi L, Altomonte M, Miracco C, Balestrazzi A, Maio M: Ipilimumab in pretreated patients with metastatic uveal melanoma: safety and clinical efficacy. Cancer Immunol Immunother. 2012, 61: 41-48. 10.1007/s00262-011-1089-0.CrossRefPubMed

Kelderman S, van der Kooij MK, van den Eertwegh AJ, Soetekouw PM, Jansen RL, van den Brom RR, Hospers GA, Haanen JB, Kapiteijn E, Blank CU: Ipilimumab in pretreated metastastic uveal melanoma patients. Results of the Dutch Working group on Immunotherapy of Oncology (WIN-O). Acta Oncol. 2013, 52: 1786-1788. 10.3109/0284186X.2013.786839.CrossRefPubMed

Mariani P, Piperno-Neumann S, Servois V, Berry MG, Dorval T, Plancher C, Couturier J, Levy-Gabriel C, Lumbroso-Le Rouic L, Desjardins L, Salmon RJ: Surgical management of liver metastases from uveal melanoma: 16 years’ experience at the institut curie. Eur J Surg Oncol. 2009, 35: 1192-1197. 10.1016/j.ejso.2009.02.016.CrossRefPubMed

10.

Leyvraz S, Suciu S, Piperno-Neumann S, Baurain J, Zdzienicki M, Testori A, Marshall E, Scheulen M, Jouary T, Negrier S, Vermorken J, Kaempgen E, Durando X, Schadendorf D, Gurunath R, Polders L, De Schaetzen G, Vanderschaeghe S, Gauthier M, Keilholz U: Randomized phase III trial of intravenous (IV) versus hepatic intra-arterial (HIA) fotemustine in patients with liver metastases from uveal melanoma: Final results of the EORTC 18021 study. J Clin Oncol. 2012, 30 (15 suppl): Abstract 8532-

11.

Huppert PE, Fierlbeck G, Pereira P, Schanz S, Duda SH, Wietholtz H, Rozeik C, Claussen CD: Transarterial chemoembolization of liver metastases in patients with uveal melanoma. Eur J Radiol. 2010, 74: e38-e44. 10.1016/j.ejrad.2009.03.064.CrossRefPubMed

12.

Klingenstein A, Haug AR, Zech CJ, Schaller UC: Radioembolization as locoregional therapy of hepatic metastases in uveal melanoma patients. Cardiovasc Intervent Radiol. 2013, 36: 158-165. 10.1007/s00270-012-0373-5.CrossRefPubMed

13.

Ausman RK, Aust JB: Isolated perfusion of the liver with HN2. Surg Forum. 1960, 10: 77-79.PubMed

14.

Rizell M, Mattson J, Cahlin C, Hafstrom L, Lindner P, Olausson M: Isolated hepatic perfusion for liver metastases of malignant melanoma. Melanoma Res. 2008, 18: 120-126. 10.1097/CMR.0b013e3282f8e3c9.CrossRefPubMed

15.

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, 21: 466-472.CrossRefPubMed

16.

Ku Y, Saitoh M, Nishiyama H, Fujiwara S, Iwasaki T, Ohyanagi H, Saitoh Y: Extracorporeal adriamycin-removal following hepatic artery infusion: use of direct hemoperfusion combined with veno-venous bypass. Nihon Geka Gakkai zasshi. 1989, 90: 1758-1764.PubMed

17.

Curley SA, Newman RA, Dougherty TB, Fuhrman GM, Stone DL, Mikolajek JA, Guercio S, Guercio A, Carrasco CH, Kuo MT: Complete hepatic venous isolation and extracorporeal chemofiltration as treatment for human hepatocellular carcinoma: a phase I study. Ann Surg Oncol. 1994, 1: 389-399. 10.1007/BF02303811.CrossRefPubMed

18.

Beheshti MV, Denny DF, Glickman MG, Bodden W, Marsh JC, Strair R, Ravikumar TS: Percutaneous isolated liver perfusion for treatment of hepatic malignancy: preliminary report. J Vasc Interv Radiol. 1992, 3: 453-458. 10.1016/S1051-0443(92)71988-5.CrossRefPubMed

19.

Pingpank JF, Hughes MS, Alexander HR, Faries MB, Zager JS, Royal R, Whitman ED, Nutting CW, Siskin GP, Agarwala SS: A phase III random assignment trial comparing percutaneous hepatic perfusion with melphalan (PHP-mel) to standard of care for patients with hepatic metastases from metastatic ocular or cutaneous melanoma. J Clin Oncol. 2010, Suppl 18: LBA8512-

20.

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J: New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009, 45: 228-247. 10.1016/j.ejca.2008.10.026.CrossRefPubMed

21.

Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, O’Brien JM, Simpson EM, Barsh GS, Bastian BC: Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature. 2009, 457: 599-602. 10.1038/nature07586.CrossRefPubMed

22.

Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T, Obenauf AC, Wackernagel W, Green G, Bouvier N, Sozen MM, Baimukanova G, Roy R, Heguy A, Dolgalev I, Khanin R, Busam K, Speicher MR, O'Brien J, Bastian BC: Mutations in GNA11 in uveal melanoma. N Engl J Med. 2010, 363: 2191-2199. 10.1056/NEJMoa1000584.CrossRefPubMedPubMedCentral

23.

Harbour JW, Onken MD, Roberson ED, Duan S, Cao L, Worley LA, Council ML, Matatall KA, Helms C, Bowcock AM: Frequent mutation of BAP1 in metastasizing uveal melanomas. Science. 2010, 330: 1410-1413. 10.1126/science.1194472.CrossRefPubMedPubMedCentral

Title: Isolated hepatic perfusion as a treatment for uveal melanoma liver metastases (the SCANDIUM trial): study protocol for a randomized controlled trial
Authors: Roger Olofsson
Lars Ny
Malin Sternby Eilard
Magnus Rizell
Christian Cahlin
Ulrika Stierner
Ulf Lönn
Johan Hansson
Ingrid Ljuslinder
Lotta Lundgren
Gustav Ullenhag
Jens Folke Kiilgaard
Jonas Nilsson
Per Lindnér
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Trials / Issue 1/2014
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/1745-6215-15-317

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Isolated hepatic perfusion as a treatment for uveal melanoma liver metastases (the SCANDIUM trial): study protocol for a randomized controlled trial

Abstract

Background

Methods/Design

Discussion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods/Design

Discussion

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2014

Feasibility, double-blind, randomised, placebo-controlled, multi-centre trial of hand-held NB-UVB phototherapy for the treatment of vitiligo at home (HI-Light trial: Home Intervention of Light therapy)

The ENHANCES study—Enhancing Head and Neck Cancer patients’ Experiences of Survivorship: study protocol for a randomized controlled trial

Improving clinical trial efficiency by biomarker-guided patient selection

A feasible strategy for preventing blood clots in critically ill patients with acute kidney injury (FBI): study protocol for a randomized controlled trial

Risk-proportionate clinical trial monitoring: an example approach from a non-commercial trials unit

Evaluating the PRASE patient safety intervention - a multi-centre, cluster trial with a qualitative process evaluation: study protocol for a randomised controlled trial