Advanced Liver Diseases - Patrick S. Kamath

Hepatocellular Carcinoma Studies

A Humanitarian Device Exemption Use Protocol of TheraSphere For Treatment of Unresectable Hepatocellular Carcinoma

Principal Investigator:
Lewis R. Roberts, M.B.Ch.B., Ph.D.
Email: roberts.lewis@mayo.edu
Secretary phone: 507-284-4823

Study Coordinator:
Teresa Mettler, RN
Phone: 507-538-0015

TheraSphere is a therapeutic device consisting of insoluble glass microspheres in which the radionuclide yttrium-90 (Y-90) is an integral constituent. This device is FDA approved as an humanitarian use device (HUD) under an humanitarian device exemption (HDE).

Specific Aims:

Primary:

• There are no hypotheses to be tested in this treatment protocol. The study has the following objectives:
  • Provide supervised access to treatment with TheraSphere to eligible patients with primary cancer to the liver who are not surgical resection candidates.
  • Evaluate patient experience and toxicities associated with TheraSphere treatment.

A Phase III, Randomized, Double-Blinded, Dummy-Controlled Study of the Efficacy and Safety of ThermoDox (Thermally Sensitive Liposomal Doxorubicin) in Combination with Radiofrequency Ablation (RFA) Compared to RFA-Alone in the Treatment of Non-Resectable Hepatocellular Carcinoma

Principal Investigator:
Lewis R. Roberts, M.B.Ch.B., Ph.D.
Email: roberts.lewis@mayo.edu
Secretary phone: 507-284-4823

Study Coordinator:
Teresa Mettler, RN
Phone: 507-538-0015

Specific Aims:

Primary:

• To determine the efficacy of systemically delivered, heat-activated liposome encapsulated doxorubicin (ThermoDox) in combination with radiofrequency ablation (RFA) by comparison to RFA-alone in the treatment of hepatocellular carcinoma (HCC) as measured by progression free survival (PFS).

Secondary:

• The secondary objectives are to assess the effect of RFA plus ThermoDox versus the control arm in the treatment of hepatocellular carcinoma as measured by:
  • Overall Survival (OS).
  • Patient-Reported Outcomes (PRO) (FHSI-8 questionnaire).
  • Time to Local Recurrence (TTLR).
  • Evaluation of safety.

A National Registry of Patients with or at Risk for Hepatobiliary Cancers, Including Hepatocellular, Cholangiocarcinoma, and Gallbladder Adenocarcinoma, and those with Normal Risk Factors

Principal Investigator:
Lewis R. Roberts, M.B.Ch.B., Ph.D.
Email: roberts.lewis@mayo.edu
Secretary phone: 507-284-4823

Study Coordinator:
Teresa Mettler, RN
Phone: 507-538-0015

Specific Aims:

Primary:

• Create a local and national registry of patients having or at risk for cancer of the liver (hepatocellular carcinoma) and cancer of the bile duct (Cholangiocarcinoma).
• To develop a resource (bank) of biospecimen (blood, tissue, stool and urine) from patients having or at risk for developing liver cancer to facilitate studies on the pathogenesis of Hepatobiliary cancers and also in order to assess the ability of new tests to detect early cancer in the cohort of patients undergoing routine surveillance for cancer.
• To administer a risk factor questionnaire to facilitate identification of risk factors for development of Hepatobiliary cancer.
• To develop immortalized cell-lines to allow future analysis of genotypes conferring risk for development of Hepatobiliary cancer. Development of immortalized cell-lines will allow future studies to accurately describe and quantify these risk factors.

Methods:

Approximately 2000 patients who are at risk for HCC (with cirrhosis or other risk factor) or Cholangiocarcinoma (with Primary Sclerosing Cholangitis or other risk factor) will give written consent and be asked to fill out a family history and risk factor questionnaire. An initial blood draw of 45 ml. will be drawn for serum, plasma and buffy coat. Liver tissue will be obtained from surgical waste tissue. After the initial blood draw, serial serum samples will be obtained at 8 week or greater intervals up to 6 times per year when the patient presents for a scheduled clinic follow-up or surveillance visit.

Stool Collection:

Several recent studies have shown that markers of cancer development can be detected in stool specimens. These techniques have been shown to apply not only to colorectal cancer, but also to other aero digestive cancers such as lung, esophageal, pancreatic and biliary cancers. Stool has the advantage of being a non-invasive method of cancer diagnosis. Patients will be asked to provide a stool specimen for this study which will be stored as up to three 30 gm aliquots.

A Two-Stage, Multi-Center, Open-Label Study of Mapatumumab (HGS1012), A Fully-Human Monoclonal Antibody To Trail-R1) In Combination With Sorafenib As A First Line Therapy In Subjects With Advanced Hepatocellular Carcinoma

Principal Investigator:
Lewis R. Roberts, M.B.Ch.B., Ph.D.
Email: roberts.lewis@mayo.edu
Secretary phone: 507-284-4823

Study Coordinator:
Teresa Mettler, RN
Phone: 507-538-0015

Specific Aims:

Stage 1:

• To evaluate the safety and tolerability of escalating doses of mapatumumab in combination with sorafenib in subjects with advanced hepatocellular carcinoma who are positive for hepatitis B surface antigen or hepatitis C antibody.
• To determine the doses of mapatumumab that can be administered in combination with sorafenib in subjects with advanced hapatocellular carcinoma.
• To determine serum mapatumumab concentrations.

Stage 2:

• To evaluate the efficacy of mapatumumab in combination with sorafenib in subjects with advanced hepatocellular carcinoma.
• To evaluate the safety and tolerability of the mapatumumab doses identified for further evaluation in Stage 1.
• To determine serum mapatumumab concentrations.