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Advanced Adult Hepatocellular CarcinomaPhase 2NCT01900002

Sorafenib Tosylate and Yttrium Y 90 Glass Microspheres in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery

A Phase 2 study testing Laboratory Biomarker Analysis, Quality-of-Life Assessment and Sorafenib in people with Advanced Adult Hepatocellular Carcinoma and BCLC Stage C Hepatocellular Carcinoma, run by M.D. Anderson Cancer Center 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 phase II trial studies how well sorafenib tosylate and yttrium Y 90 glass microspheres work in treating patients with liver cancer that cannot be removed by surgery. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Quality-of-Life Assessment and Sorafenib
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteUnited States
Study dates
13 Sep 2013to 10 Dec 2020
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

  • Subjects must be able to understand and be willing to sign the written informed consent form; a signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure
  • Life expectancy of at least 12 weeks (3 months)
  • Patients with histological or cytologically documented hepatocellular carcinoma (HCC) (documentation of original biopsy for diagnosis is acceptable if tumor tissue is unavailable) or clinical diagnosis by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic subjects is required; for subjects without cirrhosis histological confirmation is mandatory
  • Patients must have at least one tumor lesion that meets the following criteria: the lesion can be accurately measured in at least one dimension according to Response Evaluation Criteria in Solid Tumor (RECIST)
  • The target lesion(s) has not been previously treated with local therapy (such as surgery, radiation therapy, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation)
  • Patients who have received local therapy, such as surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation are eligible if the previously treated lesions have progressed or recurred can be identified as target lesions; local therapy must have been completed at least 4 weeks prior to the baseline scan
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  • Patients who have received yttrium-90 microspheres are not eligible
  • Patients who have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 1
  • Patients who are categorized under Barcelona-Clınic Liver Cancer (BCLC)-C stage
  • Cirrhosis grade of Child-Pugh class A; Child-Pugh status should be calculated based on clinical findings and laboratory results during the screening period
  • Platelet count >= 60 x 10^9/L
  • Hemoglobin >= 8.5 g/dL
  • Total bilirubin =< 2.5 mg/dl
  • Alanine transaminase (ALT) and aspartate aminotransferase (AST) =< 5 x upper limit of normal
  • Serum creatinine =< 1.5 x the upper limit of normal
  • Prothrombin time (PT)-international normalized ratio (INR) =< 2.3 or PT =< 6 seconds above control
  • All acute toxic effects of any prior treatment have resolved to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.0 grade 1 or less at the time of signing the informed consent form (ICF)
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug; post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test
  • Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least 30 days after the last dose of study drug; the definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate
  • Subject must be able to swallow and retain oral medication

Who cannot join

  • Main portal vein thrombosis (PVT)
  • Patients who are eligible for curative treatment (ablation or resection or transplantation)
  • Previous or concurrent cancer other than HCC unless without evidence of disease for 5 or more years prior to entry, except cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor
  • Tumor replacement > 70% of total liver volume based on visual estimation by the investigator OR tumor replacement > 50% of total liver volume in the presence of albumin < 3 mg/dL
  • Contraindications to angiography and selective visceral arterial catheterization
  • Any known contraindications to sorafenib including allergic reaction, pill-swallowing difficulty, uncontrolled hypertension or history of cardiac disease, significant gastrointestinal (GI) bleed within 30 days, metastatic brain disease, renal failure requiring dialysis
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  • Concomitant treatment or within 28 days of one of the following:
  • Any other systemic anticancer agent other than agents used for cancer prevention
  • Subjects who have used strong cytochrome P450 3A4 (CYP3A4) inducers (e.g., phenytoin, carbamazepine, phenobarbital, St. John's Wort [hypericum perforatum], dexamethasone at a dose of greater than 16 mg daily, or rifampin [rifampicin], and/or rifabutin) within 28 days before treatment
  • UDP glycosyltransferase 1 family, polypeptide A1 (UGT 1A1) and UDP glycosyltransferase 1 family, polypeptide A9 (UGT 1A9) substrates (e.g., irinotecan)
  • P-glycoprotein (Gp) substrates (e.g., Digoxin)
  • Prior radiation therapy to the liver
  • Prior systemic therapy for the treatment of HCC, including sorafenib
  • Any history of symptomatic pulmonary compromise, such as chronic obstructive pulmonary disease
  • Any prior intervention for, or ongoing compromise of, the ampulla of Vater or biliary-enteric anastomosis
  • Clinically evident ascites (trace ascites on imaging is acceptable)
  • Pregnant or breast-feeding patients
  • A positive serum pregnancy test within 14 days prior to treatment in women of childbearing potential
  • Uncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm Hg [NCI-CTCAE v4.0] on repeated measurement) despite optimal medical management
  • Active or clinically significant cardiac disease including:
  • Congestive heart failure-New York Heart Association (NYHA) > class II
  • Active coronary artery disease
  • Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
  • Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before treatment, or myocardial infarction within 6 months before treatment
  • Evidence or history of bleeding diathesis or uncontrolled coagulopathy
  • Subject with any pulmonary hemorrhage/bleeding event of NCI-CTCAE v4.0 grade 2 or higher within 4 weeks before treatment; any other hemorrhage/bleeding event of NCI-CTCAE v4.0 grade 3 or higher within 4 weeks before treatment
  • Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) within 6 months of informed consent
  • Presence of a non-healing wound, non-healing ulcer, or bone fracture
  • History of organ allograft. (Including corneal transplant)
  • Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial
  • Any malabsorption condition
  • Inability to comply with the protocol and/or not willing or not available for follow-up assessments

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase II Study of Sorafenib and Yttrium-90 Glass Microspheres for Advanced Hepatocellular Carcinoma, BCLC Stage C

This phase II trial studies how well sorafenib tosylate and yttrium Y 90 glass microspheres work in treating patients with liver cancer that cannot be removed by surgery. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Yttrium Y 90 glass microspheres use glass beads to carry radiation directly to tumor cells without harming normal cells. Giving sorafenib tosylate with yttrium Y 90 glass microspheres may be an effective treatment for liver cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Median progression-free survival (PFS).

SECONDARY OBJECTIVES:

  1. Overall survival (OS). II. Time to radiographic progression (TTRP). III. To evaluate the safety of the combination of sorafenib (sorafenib tosylate) and Yttrium-90; adverse events (National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [NCI-CTAE v 4.0]).

OTHER OBJECTIVES:

  1. Predictive biomarkers of response to therapy and survival: will assess pre-treatment plasma level of insulin-like growth factor 1 (IGF-1) as above, and assess its predictive ability of time to progression (TTP) and OS.

OUTLINE:

Patients receive sorafenib tosylate orally (PO) twice daily (BID). After 4 weeks, patients receive yttrium Y 90 glass microspheres intra-arterially (IA). Courses of sorafenib tosylate repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Being tested
Laboratory Biomarker Analysis, Quality-of-Life Assessment, Sorafenib, Sorafenib Tosylate, Yttrium Y 90 Glass Microspheres
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

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

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • SorafenibDrug

    Also called BAY 43-9006

    Given PO

  • Sorafenib TosylateDrug

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

    Given PO

  • Yttrium Y 90 Glass MicrospheresRadiation

    Also called TheraSphere

    Given IA

Study groups in NCT01900002
Study groupRoleWhat they receive
Treatment (sorafenib tosylate, TheraSphere)ExperimentalPatients receive sorafenib tosylate PO BID. After 4 weeks, patients receive yttrium Y 90 glass microspheres IA. Courses of sorafenib tosylate repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Drug: Sorafenib; Drug: Sorafenib Tosylate; Radiation: Yttrium Y 90 Glass Microspheres

What is being measured

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

  1. Median Progression Free Survival (PFS)

    Will be monitored using the method of Thall et al. Kaplan-Meier method will be used to estimate median progression free survival (PFS) and the 95% confidence interval. Log rank test, univariate and multivariate Cox proportional hazards regression models will be used to identify prognostic factors for progression free survival (PFS).

    Measured: From the start of therapy until failure to disease progression or death, assessed up to 4 years

Secondary outcomes (2)

  1. Median Time to Progression (TTP)

    95% credible interval will be estimated. This will be analyzed using Kaplan-Meier method, Log rank test and Cox proportional hazards regression modeling.

    Measured: Up to 4 years

  2. Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0

    To evaluate the safety of the combination of sorafenib (sorafenib tosylate) and Yttrium-90; adverse events (National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [NCI-CTAE v 4.0]) .

    Measured: Up to 4 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 Jul 2013 (estimated)
  2. Study start13 Sep 2013
  3. Primary completion10 Dec 2020
  4. Study completion10 Dec 2020

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
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01900002
Sponsor's protocol ID
2012-0870
Other IDs
NCI-2013-01667, Y-90, 2012-0870, P30CA016672
Status last verified
Dec 2021
First submitted
11 Jul 2013
Last updated
30 Dec 2021

Publications

  • Kaseb AO, Kappadath SC, Lee SS, Raghav KP, Mohamed YI, Xiao L, Morris JS, Ohaji C, Avritscher R, Odisio BC, Kuban J, Abdelsalam ME, Chasen B, Elsayes KM, Elbanan M, Wolff RA, Yao JC, Mahvash A. A Prospective Phase II Study of Safety and Efficacy of Sorafenib Followed by 90Y Glass Microspheres for Patients with Advanced or Metastatic Hepatocellular Carcinoma. J Hepatocell Carcinoma. 2021 Sep 9;8:1129-1145. doi: 10.2147/JHC.S318865. eCollection 2021.

    PubMed 34527608

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Laboratory Biomarker Analysis, Quality-of-Life Assessment and Sorafenib in people with Advanced Adult Hepatocellular Carcinoma and BCLC Stage C Hepatocellular Carcinoma, run by M.D. Anderson Cancer Center 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 32 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 30 Dec 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 30 Dec 2021). 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?

Median Progression Free Survival (PFS) (time frame: From the start of therapy until failure to disease progression or death, assessed up to 4 years). 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 NCT01900002, 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 30 Dec 2021.

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