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Hepatocellular CarcinomaPhase 2NCT00844883

Study of Sorafenib and Transarterial Chemoembolization (TACE) to Treat Hepatocellular Carcinoma

A Phase 2 study testing sorafenib and LC Bead-TACE in people with Hepatocellular Carcinoma and Hepatoma, run by Yale University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study will combine two therapies to treat patients with unresectable hepatocellular carcinoma; sorafenib, and drug eluting beads delivered intra-arterially. The purpose of the study is to establish the safety and the effectiveness of the combination therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma, Hepatoma
What is being tested?
sorafenib and LC Bead-TACE
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteUnited States
Study dates
Feb 2009to Mar 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Unresectable hepatocellular carcinoma (HCC) patients with liver-predominant disease as described in section 5.1, or patients with hepatocellular carcinoma who refuse surgery. No more than 30% of the cohort should have macrovascular invasion and/or asymptomatic extrahepatic disease. Multifocal HCC is acceptable, no diffuse HCC.
  • Age > 18 years old
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Childs class of A or B (up to 7) (see Table 5.0)
  • Adequate end-organ function as manifested by:
  • Absolute neutrophil count of > 1500/mm3 and platelets > 50,000/mm3
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  • Creatinine ≤ 2.0
  • Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) < 5 x upper limit of normal (ULN)
  • Total bilirubin of ≤ 3
  • Albumin > 2.0
  • International normalized ratio (INR) < 2.0
  • Leukocyte count >3000 cells/mm3
  • Amylase and lipase ≤ 1.5 the upper limit of normal
  • Patients who have received previous hepatic surgery , radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), or cryoablation are eligible if target lesion(s) have not been treated and local therapy completed > 6 weeks prior to entry.
  • Left ventricular ejection fraction ≥ 45%
  • Patients with asymptomatic HIV infection are not eligible
  • Willingness of male and female subjects, who are not surgically sterile or post menopausal, to use reliable methods of birth control for the duration of the study and for 30 days after the last dose of study medication.
  • Patient must have signed informed consent prior to registration on study.
  • Resolution of all acute toxic effects of any prior local treatment to Common Terminology Criteria for Adverse Events (CTCEA) Grade 1 or 0.
  • At least one tumor lesion can be accurately measured in at least one dimension according to RECIST. The lesion has not been previously treated with local therapy (such as surgery, radiation therapy, RFA, PEI, or cryoablation) unless it has shown progression in the interim.

Who cannot join

  • Patients unable to swallow oral medications
  • Prior embolization, systemic or radiation therapy for HCC (liver)
  • Tumor burden in the liver exceeding 70%.
  • Complete occlusion of the entire portal venous system
  • Ascites refractory to diuretic therapy (minimal or trace on imaging is acceptable)
  • Previous or concurrent cancer that is distinct in primary site or histology from HCC, except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis, and T1). Any cancer curatively treated > 3 years prior is permitted.
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  • Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry
  • History of bleeding within the past 4 weeks (unless deemed by PI as clinically insignificant, for ex., a brief episode of epistaxis)
  • Any contraindication to doxorubicin administration
  • Evidence of severe or uncontrolled systemic diseases,
  • Congestive cardiac failure > New York Heart Association (NYHA) class 2, myocardial ischemia within 6 months, active coronary artery disease, cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin, unstable angina, or laboratory finding that in the view of the investigator makes it undesirable for the patient to participate in the trial
  • Any prior history of hypertensive crisis or hypertensive encephalopathy
  • History of stroke or transient ischemic attack within 6 months prior to study enrollment
  • Inadequately controlled hypertension (defined as systolic blood pressure of 150/100 mmHg on antihypertensive medications) (patients with treated hypertension are eligible)
  • Significant vascular disease (e.g., aortic aneurysm, aortic dissection, peripheral vascular disease)
  • History of organ allograft
  • Presence of grade > 2 hepatic encephalopathy (see Appendix D)
  • Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an additional experimental drug
  • Evidence of bleeding diathesis or coagulopathy or on warfarin. Note: If a patient has been on coumadin for a period of 1 month and has been stable, they may be accepted into the protocol.
  • Presence of clinically evident central nervous system or brain metastases
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, anticipation of need for major surgical procedure during the course of the study
  • Vascular anatomy that precludes catheter placement or injection of LC Bead microspheres
  • Presence of collateral vessel pathways potentially endangering normal territories during embolization
  • Pregnant (positive pregnancy test) or lactating
  • Inability to comply with study and/or follow-up procedures
  • Life expectancy of less than 12 weeks
  • Child B8, B9 and C
  • ECOG ≥ 2
  • Patients with concomitant HIV infection or AIDS-related or serious acute or chronic illness
  • Presence of porto-systemic shunt
  • Severe atheromatosis
  • Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of study results
  • Active clinically serious infections (>grade 2)
  • Patients receiving therapy for hepatitis A, B, or C.
  • Patients with obvious and/or symptomatic extrahepatic disease. Findings of uncertain significance, such as lung lesions less than 10 mm in diameter or enlarged periportal lymph nodes will not exclude patients, however, findings highly suspicious for metastatic HCC will exclude patients from this study.
  • Any contraindication for an arterial procedure such as impaired clotting tests (platelet count < 50.000/mm3 or prothrombin activity < 50 percent)
  • Any contraindication for systemic chemotherapy administration (serum bilirubin > 3mg/dL, leukocyte count < 3.000 cells/mm3)
  • Any contraindication for sorafenib administration

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The Johns Hopkins Hospital

    Baltimore, Maryland, 21287

Other trials in United States

About this study

Official title: Phase II Trial of Sorafenib Combined With Doxorubicin Eluting Bead-Transarterial Chemoembolization (LC Bead-TACE) for Patients With Hepatocellular Carcinoma

This study will combine two therapies to treat patients with unresectable hepatocellular carcinoma; sorafenib, and drug eluting beads delivered intra-arterially. The purpose of the study is to establish the safety and the effectiveness of the combination therapy. The investigators hypothesize that the combination of the two therapies will not result in greater toxicities to patients than that expected for either therapy given alone.

Being tested
sorafenib, LC Bead-TACE
Keywords
primary liver cancer, sorafenib, Nexavar, doxorubicin, drug eluting beads, transarterial chemoembolization
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • sorafenibDrug

    Also called sorafenib (Nexavar)

    sorafenib: given 400 mg twice per day for as long as it is beneficial

  • LC Bead-TACEProcedure or surgery

    Also called LC Beads manufactured by Biocompatibles

    LC Beads loaded with doxorubicin

    Doxorubicin loaded LC Beads: given intra-arterially into the liver, up to fours times in a 6 month period

Study groups in NCT00844883
Study groupRoleWhat they receive
sorafenib and drug eluting beadsExperimentalsingle arm
Receives: Drug: sorafenib; Procedure: LC Bead-TACE

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety Will be Assessed by Grading Toxicities Reported at Intervals Throughout the Study. Higher Grade Toxicities Will be Assessed for Their Degree of Relatedness to the Study Treatment.

    Treatment toxicities assessed by CTCAE v3.0 were stratified by cycle - patients on Cycle 1, and patients on Cycles 2-5 or more. 50 patients were reviewed for toxicities for Cycle 1, and all 50 patients experienced at least one adverse event during this time period.

    Measured: 6 weeks (Cycle 1)

  2. Safety Will be Assessed by Grading Toxicities Reported at Intervals Throughout the Study. Higher Grade Toxicities Will be Assessed for Their Degree of Relatedness to the Study Treatment.

    Treatment toxicities assessed by CTCAE v3.0 were stratified by cycle - patients on Cycle 1, and patients on Cycles 2-5 or more.

    Measured: 2 years (Cycles 2-5+)

Secondary outcomes (5)

  1. Efficacy Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) to Determine Response and Disease Control Rate

    Efficacy as assessed by radiographic tumor response using the RECIST criteria at baseline and at 6 months post the initiation of treatment. 33 out of the original 50 patients were evaluable at this time point, with 17 out of the 50 exiting prior to 6 months or were not assessable by RECIST criteria.

    Complete response (CR): Disappearance of all lesions targeted with therapy Partial Response (PR): at least 30% decrease in sum of longest diameter (LD) of targeted lesions Progressive Disease (PD): at least 20% increase in the sum of LD of targeted lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or sufficient increase to qualify for PD

    Measured: 6 months

  2. Efficacy Assessed by European Association for the Study of the Liver (EASL) Criteria to Determine Response and Disease Control Rate

    Efficacy as assessed by radiographic tumor response using the EASL criteria at baseline and at 6 months post the initiation of treatment.

    Complete response (CR): 100% tumor necrosis Partial Response (PR): more than 50% tumor necrosis Progressive Disease (PD): increase in tumor enhancement by more than 25% Stable Disease (SD): Cases that do not qualify for one of the above criteria

    Measured: 6 months

  3. Efficacy - Median TTP After Combination Treatment With Sorafenib and TACE

    Time to progression (TTP) - defined as the time from initiation of therapy to disease progression (radiological). Median TTP calculated for all subjects and stratified by Barcelona Clinic Liver Cancer (BCLC) staging.

    46 patients out of 50 were reviewed for this outcome. 3 patients were excluded because they underwent liver transplantation and 1 patient was excluded for hepatic resection.

    Measured: 3 years

  4. Efficacy - Overall Survival (OS) After Combination Treatment With Sorafenib and TACE

    Overall survival was assessed with Kaplan-Meier estimates of survival, and the Mantel-Cox log-rank test was used to determine differences in survival.

    All 50 patients were included in survival analyses as all 50 received at least one dose of sorafenib.

    Measured: 3 years

  5. Efficacy - Factors Associated With Overall Survival (OS) After Combination Treatment With Sorafenib and TACE

    Overall survival was assessed with Kaplan-Meier estimates of survival, and the Mantel-Cox log-rank test was used to determine differences in survival.

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Feb 2009 (estimated)
  2. Study startFeb 2009
  3. Primary completionMar 2015
  4. Study completionMar 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00844883
Sponsor's protocol ID
J08110
Status last verified
Oct 2021
First submitted
4 Feb 2009
Last updated
11 Nov 2021
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing sorafenib and LC Bead-TACE in people with Hepatocellular Carcinoma and Hepatoma, run by Yale University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety Will be Assessed by Grading Toxicities Reported at Intervals Throughout the Study. Higher Grade Toxicities Will be Assessed for Their Degree of Relatedness to the Study Treatment. (time frame: 6 weeks (Cycle 1)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00844883.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Nov 2021.

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