Treatment of Patients with Hepatic Neuroendocrine Metastases using Drug-Eluting Bead Embolization
This research is being done to study the use of LC Beads as a way of delivering the chemotherapy drug doxorubicin to the liver of people with neuroendocrine tumors that have spread to the liver. Traditionally, neuroendocrine tumors that spread to the liver are hard to treat because it takes high levels of chemotherapy to kill the cancer cells. Unfortunately, giving the chemotherapy at such high doses in the bloodstream has many side effects. One way to reduce the side effects from the chemotherapy is to give it directly into the tumor by placing a catheter into the artery near the tumor in the liver. This procedure is called TACE (transarterial chemoembolization).
Inclusion criteria for the study will include the following:Patient chooses to participate and has signed the informed consent documentAge above 18 years oldDiagnosis of hepatic neuroendocrine metastases not suitable for radical therapies such as resection or liver transplantation. Patient with preserved liver function (Child-Pugh A-B class) without significant liver decompensation.Eastern Cooperative Oncology Group (ECOG) Performance Status score 0-2Histologically proven neuroendocrine tumorRecent interval progression of hepatic liver metastasesSerum bilirubin level less than equal to 3.0 mg/dlPredominant to the liver disease, but extrahepatic disease is not an exclusionTumors are hypervascular based on visual estimation by investigatorExclusion criteria include the following:Patients previously treated with any anti-cancer therapy for hepatic neuroendocrine metastases except previous surgical therapy.Patients with another active primary tumor.Advanced liver disease: Child-Pugh's C class or active gastrointestinal bleeding, encephalopathy or ascites (trace ascites is accepted). Bilirubin levels greater than 3mg/dlAST, ALT, alkaline phosphatase greater than 5 times the upper limit of normalSerum creatinine greater than 2.0 mg/dLAlbumin less than equal to 2.0 g/dLDiffuse hepatic neuroendocrine metastases meaning massive ill-defined tumor involvement measuring greater than 90% tumor burden will be excluded.Any contraindication for hepatic embolization procedures: porto-systemic shunt, hepatofugal blood flow; impaired clotting tests (platelet count less than 50,000/mm3, an INR of 1.8 or higher, or PTT of 39 seconds or greater), renal failure, severe peripheral vascular disease precluding catheterization; Any contraindication for doxorubicin administration (serum bilirubin greater than 5mg/dL, leukocyte count less than 1500 cells/mm3,).Clinically evident ascites. (Note: A radiographic finding of trace ascites on imaging is acceptable.Any continuing complication or prior cancer therapy that have not improved or resolved prior to 21 days before the first treatment with the Drug-eluting beads (if the investigator determines that the continuing complication will compromise the safety of the patient following treatment with Drug-eluting beads).Concurrent enrollment in another clinical study.In the judgment of the physician, significant life-threatening extrahepatic disease.Predominant extrahepatic liver diseaseComplete occlusion of the entire portal venous systemEvidence of cirrhosis or portal hypertensionWomen who are pregnant.Allergy to contrast media.Patients intolerant to occlusion procedures.Vascular anatomy or blood that precludes catheter placement or emboli injectionPresence or likely onset of hemorrhagePresence of severe atheromatous diseasePresence of feeding arteries smaller than distal branches from which they emergePresence of patent extra-to-intracranial anastomoses or shuntsPresence of collateral vessel pathways potentially endangering normal territories during embolizationPresence of end arteries leading directly to cranial nervesPresence of arteries supplying the lesion not large enough to accept LC Bead Vascular resistance peripheral to the feeding arteries precluding passage of LC Bead Embolic AgentDo not use LC Bead in the following applications:Embolization of large diameter arteriovenouus shunts The pulmonary arterial vasculatureUse in any vasculature where the use of LC Bead could pass directly into the internal carotid artery or the above listed vessels
In this study, tiny plastic beads (LC Beads) will be loaded (mixed) with the chemotherapy drug (doxorubicin) and delivered into the liver close to the tumor(s) in the same way as in the TACE procedure. It is hoped that the use of the LC Beads will keep the chemotherapy attached to them in the tumor longer and kill more of the cancer cells. It is also hoped that by keeping the chemotherapy in the tumor that the typical side effects to the rest of the body will be less. Endpoints will be safety, tumor response, and survival.
05/23/2013 04:06 AM