The project, the Study of Hepatic Arterial Infusion of Melphalan for Malignancy in the liver, can be divided in two parts due to two separate clinical trials. First, NCI 04-C-0273 entitled A Phase II Study of Hepatic Arterial Infusion of Melphalan with Venous Filtration via Peripheral Hepatic Perfusion (PHP) for Unresectable Primary and Metastatic Cancers to the Liver. This trial enrolls patients with primary liver or metastatic disease to the liver. To date 57 patients have enrolled in this study. Each patient has a varied histology including but not limited to metastatic colorectal cancer, primary liver cancer, metastatic ocular melanoma and metastatic neuroendocrine tumors. Goals of this trial are to find which histologies may benefit from this treatment. The second half of the project involves NCI 06-C-0088, A Random-Assignment Study of Hepatic Arterial Infusion of Melphalan with Venous Filtration via Peripheral Hepatic Perfusion (PHP) (Delcath System) Versus Best Alternative Care for Ocular and Cutaneous Melanoma Metastatic to the Liver. This trial is a multi-center phase III trial with NCI as the coordinating center. Currently nine centers are approved and a large effort has been spent in 2008 and 2009 getting this centers educated, credentialed and mentored in their first procedures. Accrual for this trial is completed with 93 patients enrolled at the nine participating centers. During the course of 2011, peripheral hepatic perfusions were completed both at the clinical center and at six other participating institutions. The procedure takes place in the special procedures unit also known as interventional radiology. Venous and Arterial Access is obtained after informed consent. A diagnostic angiogram is completed to define anatomy and ensure infusion of Melphalan will only be to the liver. Frequently, embolizations of the gastro-duodenal artery are necessary to ensure the Melphalan only bathes the liver tumor. Once the anatomy is deemed favorable, then the arterial catheters are placed in the common hepatic artery and the patient is anti-coagulated. The hepatic artery is infused with 3mg/kg (ideal body weight) of Melphalan after the Delcath venous device is used to isolate the blood flow from the liver. This catheter then removes the hepatic effluent via veno-veno bypass and circulate the blood through two filters and back into the patient. After the chemotherapy has been infused, thirty minutes of just filtration is performed. The arterial infusion catheter is removed while the sheath is left in place until the anti-coagulation can be reversed. With this novel treatment strategy, the project hopes to provide an effective means of treating a fatal condition. With the multi-center trial, the technology has been shared with other cancer centers and is being tested across the Unites States. In January, the data was collected and analyzed due to number of events which was predetermined. As presented at ASCO in June, the median hepatic progression free survival (HPFS) for patients randomized to PHP was 245 days and HPFS for the best available care group was 49 days p<.001. Preliminary data in the form of abstracts and posters have been presented and are listed below with title, authors and locations: 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.JFPingpank, MS Hughes, MB Faries, JS Zager, HR Alexander, RE Royal, CW Whitman, CW Nutting, GP Siskin, SS Agarwala American Society of Clinical Oncology, Chicago, IL June 5, 2010 No definitive manuscripts were published yet. One manuscript is in draft form for the phase II and phase III. The company who sponsored the trial is preparing for resubmission to the FDA. The manuscript delays have stemmed from the Sponsor, Delcath, migrating all the data into a new database in order to help their resubmission efforts. Monitoring of the transferred data was still underway into this summer.
