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Liver CancerPhase 1NCT01075113

Sorafenib and Vorinostat in Treating Patients With Advanced Liver Cancer

A Phase 1 study testing sorafenib tosylate and vorinostat in people with Liver Cancer, run by Virginia Commonwealth University at 2 sites 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 phase I trial is studying the side effects and best dose of vorinostat when given together with sorafenib tosylate in treating patients with advanced liver cancer. Sorafenib tosylate and vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Liver Cancer
What is being tested?
sorafenib tosylate and vorinostat
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
2 sitesUnited States
Study dates
10 Aug 2010to 18 Jul 2019
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Diagnosis of HCC by biopsy-proven pathologic diagnosis or by clinical criteria as defined below:
  • Clinical criteria to be met if patient has a history of cirrhosis or chronic hepatitis B infection:
  • Imaging abnormalities > 1 cm in size with classic enhancement by magnetic resonance imaging (MRI) or triple-phase computed tomography (CT) scan
  • Alpha-fetoprotein (AFP) of any value
  • Performance status Eastern Cooperative Oncology Group (ECOG) =< 1
  • If cirrhosis, Child-Pugh classification A or B
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  • Total bilirubin =< 3.0 mg/dL
  • Creatinine =< 1.5 x upper limit of normal for the laboratory
  • International normalized ratio (INR) =< 1.7 (if not due to anticoagulants)
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelets >= 80,000/mm^3
  • Hemoglobin (Hgb) >= 8.5 g/dL (transfusion or erythropoietin-like substances not permitted prior to baseline evaluation)
  • Any prior therapies such as surgery, chemoembolization, radiofrequency ablation, and alcohol injection are allowed as long as toxicity from such prior therapy is =< grade 1
  • Prior sorafenib is allowed as long as toxicity from ongoing is ≤ grade 2 and prior intolerance of 400 mg sorafenib PO daily is felt amenable, by the principal investigator, to supportive care measures or dose modifications.
  • Measurable or evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version (v) 1.1 mRECIST or elevated AFP
  • Ability to understand and willingness to sign a written informed consent; a signed informed consent must be obtained prior to any study specific procedures
  • Women of childbearing potential must have a negative pregnancy test performed within 2 weeks prior to the start of treatment
  • Women of childbearing potential and men must agree to use a medically accepted form of birth control for the duration of study participation and for 4 months following completion of study treatment

Who cannot join

  • Candidate for curative therapy including surgical resection or orthotopic liver transplantation
  • Known central nervous system metastasis
  • Any investigational agent within 4 weeks of first dose of study treatment
  • Known intolerance of vorinostat
  • Unable to swallow medication
  • Unable to swallow medication; suspected malabsorption
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  • Active alcohol abuse
  • Contraindication to antiangiogenic agents, including:
  • Pulmonary hemorrhage/bleeding event >= grade 2 within 4 weeks of first dose of study drug
  • Any other hemorrhage/bleeding event >= grade 3 within 4 weeks of first dose of study treatment
  • Serious non-healing wound, ulcer, or bone fracture
  • Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months; hepatic portal vein thrombus is not considered an exclusion criterion
  • Major cardiac dysfunction, such as uncontrolled angina, congestive heart failure with New York Heart Association (NYHA) class III or higher, known left ventricular ejection fraction less than 40%
  • Systolic blood pressure > 160 mmHg or diastolic pressure > 90 mmHg despite optimal medical management
  • Significant lung disease (oxygen [O2] saturation less than 88% in room air)
  • Serious uncontrolled infection; known human immunodeficiency virus (HIV)-seropositivity requiring retroviral therapy, or diagnosis of acquired immune deficiency syndrome (AIDS); diagnosis of chronic hepatitis B or C allowed
  • Medical, psychological, or social conditions that, in the opinion of the investigator, may increase the patient's risk or interfere with the patient's participation in the study or hinder evaluation of the study results

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Hunter Holmes McGuire VA Medical Center

    Richmond, Virginia, 23249

  • Virginia Commonwealth University/Massey Cancer Center

    Richmond, Virginia, 23298

Other trials in United States

About this study

Official title: A Phase I Study of Sorafenib and Vorinostat in Advanced Hepatocellular Carcinoma

This phase I trial is studying the side effects and best dose of vorinostat when given together with sorafenib tosylate in treating patients with advanced liver cancer. Sorafenib tosylate and vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor.

Read the detailed description

Outline: This is a dose-escalation study of vorinostat. The purpose of this research study is to test the safety and effectiveness of a combination of two cancer drugs, sorafenib (Nexavar) and vorinostat (Zolinza), in advanced liver cancer (hepatocellular carcinoma). Advanced means that the cancer has spread too far to consider surgery. Approximately 19 people will take part in this study.

After enrollment of 6 patients at sorafenib 400 mg orally twice a day and vorinostat 300 mg orally, only 2 of the 6 patients were evaluable for DLT (no DLTs). The other 4 patients were not evaluable for DLT because of required dose modifications. Because of this dose modification need, Cohort A has been modified to include 2 dose levels: Dose level A-1a (sorafenib 400 mg orally twice a day and vorinostat 200 mg orally once a day) and dose level A1 (sorafenib 400 mg orally twice a day with vorinostat 100 mg orally once a day). The starting dose upon reopening after approval of this version will be dose level A-1a. Dose level A1 will only be used if dose level A-1a is not tolerable.

Conditions
Liver Cancer
Being tested
sorafenib tosylate, vorinostat
Keywords
adult primary hepatocellular carcinoma, advanced adult primary liver cancer, recurrent adult primary liver cancer
Medical subject headings
Liver Neoplasms, Carcinoma, Hepatocellular

What participants receive

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

  • sorafenib tosylateDrug

    Also called BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar

    Given orally

  • vorinostatDrug

    Also called L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

    Given orally

Study groups in NCT01075113
Study groupRoleWhat they receive
Arm AExperimentalSorafenib + Vorinostat. Patients receive sorafenib tosylate PO BID continuously and vorinostat PO QD, for 5 days each week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohort A has only one dose level: sorafenib 400 mg orally twice a day with vorinostat 300 mg orally. Cohort A was modified to include 2 dose levels: Dose level A1 (sorafenib 400 mg orally twice a day and vorinostat 200 mg orally once a day) and dose level A-1 (sorafenib 400 mg orally twice a day with vorinostat 100 mg orally once a day). The starting dose upon reopening after approval of this version will be dose level A-1a. Dose level A1 will only be used if dose level A-1a is not tolerable.
Receives: Drug: sorafenib tosylate; Drug: vorinostat
Arm B CLOSEDExperimentalReduced Dose 200mg Sorafenib + Vorinostat. Patients receive sorafenib tosylate PO BID continuously and vorinostat PO QD, for 5 days each week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohort B has 2 dose levels starting at the second dose level (sorafenib 200 mg orally twice a day with vorinostat 400 mg orally). Cohort B has been closed. Cohort B was intended to evaluate the possibility of dose intensification of vorinostat when patients were unable to tolerate standard dose sorafenib, and required dose-reduced sorafenib. The patients accrued to date in Cohort B were unable to tolerate therapy, and it has been determined that dose intensification of vorinostat is not possible, despite reducing the dose of sorafenib.
Receives: Drug: sorafenib tosylate; Drug: vorinostat

What is being measured

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

  1. Determine the appropriate Doses for the combination of sorafenib tosylate and vorinostat appropriate for phase II study in hepatocellular carcinoma (HCC).

    Identify the maximum tolerated dose of the combination regimen of vorinostat and sorafenib to study further for efficacy of treatment for hepatocellular carcinoma

    Measured: 4 weeks

Secondary outcomes (2)

  1. Adverse events will be characterized in terms of nature, severity, attribution, onset and resolution according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0.

    Safety, tolerance, and toxicity of the combination of sorafenib tosylate and vorinostat in patients with HCC. Observe toxicities experienced by patients treated in cohorts of escalating doses of the drug combination.

    Measured: Up to 30 days post-treatment

  2. Anti-tumor effects of the combination of sorafenib tosylate and vorinostat

    Tumor masses will be evaluated for response according to the RECIST Criteria. Summarized using descriptive statistics for each cohort, along with their corresponding 95% confidence intervals.

    Measured: Up to 6 years

Timeline

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

  1. First posted24 Feb 2010 (estimated)
  2. Study start10 Aug 2010
  3. Primary completion2 Feb 2017
  4. Study completion18 Jul 2019

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01075113
Sponsor's protocol ID
MCC-12122
Other IDs
NCI-2010-00185
Status last verified
Aug 2019
First submitted
19 Feb 2010
Last updated
20 Aug 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Gordon SW, McGuire WP 3rd, Shafer DA, Sterling RK, Lee HM, Matherly SC, Roberts JD, Bose P, Tombes MB, Shrader EE, Ryan AA, Kmieciak M, Nguyen T, Deng X, Bandyopadhyay D, Dent P, Poklepovic AS. Phase I Study of Sorafenib and Vorinostat in Advanced Hepatocellular Carcinoma. Am J Clin Oncol. 2019 Aug;42(8):649-654. doi: 10.1097/COC.0000000000000567.

    PubMed 31305287

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing sorafenib tosylate and vorinostat in people with Liver Cancer, run by Virginia Commonwealth University at 2 sites 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 18 inclusion and 17 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 20 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Determine the appropriate Doses for the combination of sorafenib tosylate and vorinostat appropriate for phase II study in hepatocellular carcinoma (HCC). (time frame: 4 weeks). 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 NCT01075113, which also lists 1 linked publication.

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 20 Aug 2019.

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