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

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Sorafenib

Yttrium-90 (Y-90)

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Subjects with primary hepatocellular carcinoma, intended for liver transplantation.

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Northwestern Memorial Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

A: Y-90 alone

B: Sorafenib + Y-90

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

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.

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

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.

Full Information

NCT ID

NCT00846131

First Posted

February 16, 2009

Last Updated

September 13, 2016

Sponsor

Northwestern University

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00846131

Brief Title

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

Official Title

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.

Study Type

Interventional

2. Study Status

Record Verification Date

September 2016

Overall Recruitment Status

Completed

Study Start Date

February 2009 (undefined)

Primary Completion Date

July 2015 (Actual)

Study Completion Date

September 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Northwestern University

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatocellular Carcinoma

Keywords

Subjects with primary hepatocellular carcinoma, intended for liver transplantation.

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

A: Y-90 alone

Arm Type

Active Comparator

Arm Description

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

Arm Title

B: Sorafenib + Y-90

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Sorafenib

Other Intervention Name(s)

BAY 54-9085 is the tosylate salt of BAY 43-9006; NEXAVAR®

Intervention Description

Randomized to Y-90 ± Sorafenib

Intervention Type

Drug

Intervention Name(s)

Yttrium-90 (Y-90)

Other Intervention Name(s)

Radioembolization, Therasphere

Intervention Description

Patients undergo radioembolization with Yttrium 90 microspheres by hepatic artery infusion

Primary Outcome Measure Information:

Title

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

Description

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.

Time Frame

Up to one year

Secondary Outcome Measure Information:

Title

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

Description

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.

Time Frame

up to 1 year

Title

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

Description

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.

Time Frame

up to 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Laura Kulik, MD

Organizational Affiliation

Northwestern University, Northwestern Memorial Hospital, Northwestern Medical Faculty Foundation

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Riad Salem, MD

Organizational Affiliation

Northwestern University, Northwestern Memorial Hospital, Northwestern Medical Faculty Foundation

Official's Role

Principal Investigator

Facility Information:

Facility Name

Northwestern Memorial Hospital

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

24681342

Citation

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.

Results Reference

result

PubMed Identifier

23703789

Citation

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.

Results Reference

result

Hepatocellular Carcinoma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial