Y-90 Alone or With Sorafenib for Pre-Transplant Hepatocellular Carcinoma

NCT00846131 | Completed Phase 1 DMC

• 2 other identifiers: NU08I4STU00005761
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

A research study to determine the safety, efficacy, and tolerability of Therasphere® (also known as Y-90, or Y-90 Therasphere) combined with or without sorafenib (Nexavar®), in patients with hepatocellular carcinoma (HCC, or liver cancer), awaiting liver transplantation.

Conditions

Hepatocellular Carcinoma

Keywords

Subjects with primary hepatocellular carcinoma, intended for liver transplantation.

Outcome Measures

Primary Outcomes (1)

• To Evaluate sorafenib as an adjunct to Y-90 for control of HCC as a bridge/downstage to transplant

  Subjects randomized to receive Sorafenib take the drug for 2 weeks before treatment with Y90. They have imaging (CT/MRI) 2 weeks after starting Sorafenib then are treated. Post-treatment patients have blood drawn and adverse event evaluation at 2 weeks, 4 weeks, 6 weeks, and then every 6 weeks up to 1 year or time of transplant. Repeat imaging is done at 4 weeks, and then every 3 months post-treatment. Subjects not receiving Sorafenib are treated with Y90 and then are evaluated post-treatment the same as the subjects that receive the drug.

  Up to one year

Secondary Outcomes (2)

• To characterize the toxicity profile of sorafenib and Y90 using NCI CTC toxicity grading scales.

  up to 1 year

• To identify predictive and prognostic markers of how the liver cancer will respond to treatment.

  up to 1 year

Study Arms (2)

A: Y-90 alone

ACTIVE COMPARATOR

Patients randomized to Arm A will proceed to Y-90 treatment alone in the Northwestern standard of care procedure

Drug: Yttrium-90 (Y-90)

B: Sorafenib + Y-90

EXPERIMENTAL

Patients randomized to Arm B will start sorafenib at a dose of 400 mg twice daily for bilirubin ≤ 1.5 x ULN and 200 mg twice daily for bilirubin \> 1.5 x ULN to ≤ 3 x ULN. After 14 days of sorafenib therapy (+/- 3 days) patients will proceed to Y-90 in the Northwestern standard of care procedure

Drug: Sorafenib; Drug: Yttrium-90 (Y-90)

Interventions

Sorafenib DRUG

Randomized to Y-90 ± Sorafenib

Also known as: BAY 54-9085 is the tosylate salt of BAY 43-9006; NEXAVAR®

B: Sorafenib + Y-90

Yttrium-90 (Y-90) DRUG

Patients undergo radioembolization with Yttrium 90 microspheres by hepatic artery infusion

Also known as: Radioembolization, Therasphere

A: Y-90 alone; B: Sorafenib + Y-90

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult \> 18 years olf of either gender
• Diagnosis of HCC confirmed by biopsy, CT, or MRI
• Able to carry out activities of daily living, awake \>50% of waking hours
• Meets eligibility for liver transplantation
• No prior treatment for HCC
• Ability to understand and sign the informed consent
• Child-bearing women and any men agree to use two forms of birth control (one of which should be a barrier method) during the course of therapy and for 8 weeks afterward.

You may not qualify if:

• Less than or = 18 years old
• Ineligible for transplant due to comorbid disease
• Renal Failure requiring dialysis of any kind
• Severe Cardiac disease
• History of a stroke
• Evidence of metastatic disease- or tumors that have spread outside the liver
• Known human immunodeficiency virus (HIV) infection
• Uncontrolled blood pressure (systolic \> 160) despite medication(s)
• Major surgery within 4 weeks prior to the screening visit
• Active clinically serious infection
• Serious non-healing wound, ulcer, or bone fracture.
• History of gastrointestinal bleeding (GIB) within 6 weeks prior to the screening visit
• Prior transplant of any kind
• Must be able to swallow oral pills, tablets or capsules of any size
• Use of St. John's Wort or rifampin (rifampicin).

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Related Publications (2)

• Kulik L, Vouche M, Koppe S, Lewandowski RJ, Mulcahy MF, Ganger D, Habib A, Karp J, Al-Saden P, Lacouture M, Cotliar J, Abecassis M, Baker T, Salem R. Prospective randomized pilot study of Y90+/-sorafenib as bridge to transplantation in hepatocellular carcinoma. J Hepatol. 2014 Aug;61(2):309-17. doi: 10.1016/j.jhep.2014.03.023. Epub 2014 Mar 27.

  PMID: 24681342 RESULT

• Vouche M, Kulik L, Atassi R, Memon K, Hickey R, Ganger D, Miller FH, Yaghmai V, Abecassis M, Baker T, Mulcahy M, Nayar R, Lewandowski RJ, Salem R. Radiological-pathological analysis of WHO, RECIST, EASL, mRECIST and DWI: Imaging analysis from a prospective randomized trial of Y90 +/- sorafenib. Hepatology. 2013 Nov;58(5):1655-66. doi: 10.1002/hep.26487. Epub 2013 Oct 1.

  PMID: 23703789 RESULT

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Sorafenib; Yttrium-90

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Laura Kulik, MD

  Northwestern University, Northwestern Memorial Hospital, Northwestern Medical Faculty Foundation

  PRINCIPAL INVESTIGATOR

• Riad Salem, MD

  Northwestern University, Northwestern Memorial Hospital, Northwestern Medical Faculty Foundation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 16, 2009
• First Posted: February 18, 2009
• Study Start: February 1, 2009
• Primary Completion: July 1, 2015
• Study Completion: September 1, 2016
• Last Updated: September 15, 2016

Record last verified: 2016-09

Locations

US (1)