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

13 september 2016 bijgewerkt door: Laura Kulik, Northwestern University

A Single-Center Proof of Concept Pilot Study to Evaluate the Safety, Efficacy, and Tolerability of Sorafenib Combined With Therasphere in Subjects With Hepatocellular Carcinoma Awaiting Liver Transplantation.

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.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

Because Hepatocellular carcinoma (HCC) grows by forming new blood vessels liver transplant (OLT) offers the best chance for long term survival. However, with the growing number of patients who require OLT, prolonged wait list times often lead to drop out from the transplant list due to tumor progression. Some patients are granted an "upgrade",within the generally accepted guidelines for transplant eligibility, in order to expedite the access of patients with early HCC to transplantation before tumor progression. The use of therapies like radioembolization also known as Yttrium-90 ([Y-90] a procedure where very small beads coated with radiation are injected directly into the tumor through an artery in your groin) while awaiting OLT has become common at most transplant centers, including Northwestern, to help patients reach transplant. Additionally, these treatments are being used to move patients to a status eligible for transplant. We are studying whether a combination approach with systemic therapy and therapy applied directly to the liver, will be more successful than a single therapy . Angiogenesis (a process involving the growth of new blood vessels from pre-existing vessels) plays an important role in the early stages of HCC. A decrease in angiogenesis both locally within the treated tumor as well as in any existing tumor cells, not yet detected, would hopefully decrease the incidence of post transplant recurrence of HCC. All subjects enrolled in this study will be treated with the use of Therasphere, Y-90, which is composed of nonbiodegradable glass microspheres coated with the radioactive compound Y-90 which are injected into the hepatic artery. The concentrated radioactive microspheres within the tumor lead to "inside-out" radiation. Half of the subjects will be treated with sorafenib (NEXAVAR®) in conjunction with Y-90. The determination of which subjects will receive sorafenib will be made randomly, like the flip of a coin. Sorafenib works by slowing the growth of the tumor cell , attacking the tumor from the outside. Researchers hope to determine whether the subjects treated with sorafenib have an overall improved response to liver directed therapy with Y-90 Therasphere.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

24

Fase

  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Verenigde Staten
    • Illinois
      • Chicago, Illinois, Verenigde Staten, 60611
        • Northwestern Memorial Hospital

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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).
  • Currently being treated with Interferon and/or Ribavirin therapy due to the thrombocytopenias, lymphopenias and anemias observed with use of these two medications.
  • Known or suspected allergy to sorafenib or any agent given in the course of this trial.
  • Any malabsorption problem
  • Pregnancy or lactation. Women of childbearing potential must have a negative pregnancy test 7 days prior to beginning therapy.
  • No potential living donor transplant (LDT-donor identified and worked up by the time of randomization into this study. If a living donor is later identified- the subject will be allowed to continue in the study. Sorafenib will be stopped at a minimum of 7 days prior to transplant surgery.
  • Active alcohol use, drug use, or a psychiatric disease that would, in the opinion of the PI or a subinvestigator (sub-I), prevent the subject from complying with the study protocol and/or endanger the subject during their participation in the study
  • Inability of the potential subject to read, understand and sign the informed consent document

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Actieve vergelijker: A: Y-90 alone
Patients randomized to Arm A will proceed to Y-90 treatment alone in the Northwestern standard of care procedure
Geneesmiddel: Yttrium-90 (Y-90)
Patients undergo radioembolization with Yttrium 90 microspheres by hepatic artery infusion
Andere namen:
  • Radio-embolisatie
  • Therasphere
Experimenteel: B: Sorafenib + Y-90
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
Geneesmiddel: Yttrium-90 (Y-90)
Patients undergo radioembolization with Yttrium 90 microspheres by hepatic artery infusion
Andere namen:
  • Radio-embolisatie
  • Therasphere
Geneesmiddel: Sorafenib
Randomized to Y-90 ± Sorafenib
Andere namen:
  • BAY 54-9085 is the tosylate salt of BAY 43-9006; NEXAVAR®

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
To Evaluate sorafenib as an adjunct to Y-90 for control of HCC as a bridge/downstage to transplant
Tijdsspanne: Up to one year
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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
To characterize the toxicity profile of sorafenib and Y90 using NCI CTC toxicity grading scales.
Tijdsspanne: up to 1 year
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 1 year
To identify predictive and prognostic markers of how the liver cancer will respond to treatment.
Tijdsspanne: up to 1 year
All subjects are evaluated with lab work and adverse event assessment at 2, 4, and 6 weeks post-treatment, and then every 6 weeks up to 1 year or when they receive transplant.
up to 1 year

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Northwestern University

Medewerkers

National Cancer Institute (NCI)

Onderzoekers

  • Hoofdonderzoeker: Laura Kulik, MD, Northwestern University, Northwestern Memorial Hospital, Northwestern Medical Faculty Foundation
  • Hoofdonderzoeker: Riad Salem, MD, Northwestern University, Northwestern Memorial Hospital, Northwestern Medical Faculty Foundation

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 februari 2009

Primaire voltooiing (Werkelijk)

1 juli 2015

Studie voltooiing (Werkelijk)

1 september 2016

Studieregistratiedata

Eerst ingediend

16 februari 2009

Eerst ingediend dat voldeed aan de QC-criteria

17 februari 2009

Eerst geplaatst (Schatting)

18 februari 2009

Updates van studierecords

Laatste update geplaatst (Schatting)

15 september 2016

Laatste update ingediend die voldeed aan QC-criteria

13 september 2016

Laatst geverifieerd

1 september 2016

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • NU08I4
  • STU00005761 (Andere identificatie: Northwestern University IRB)

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