Sorafenib and Yttrium-90 Glass Microspheres for Advanced Hepatocellular Carcinoma (HCC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01900002
Recruitment Status : Active, not recruiting
First Posted : July 16, 2013
Last Update Posted : January 25, 2018
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
The goal of this clinical research study is to learn about the safety of combining sorafenib with TheraSphere in the treatment of patients with advanced liver cancer.

Condition or disease Intervention/treatment Phase
Liver Cancer Drug: Sorafenib Radiation: Yttrium-90 Microspheres Behavioral: Follow-Up Phone Calls Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Sorafenib and Yttrium-90 Glass Microspheres for Advanced Hepatocellular Carcinoma, BCLC Stage C
Actual Study Start Date : September 13, 2013
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Sorafenib and Yttrium-90
Starting dose of Sorafenib 400 mg 2 times a day starting on Day 1 of Cycle 1, 4 weeks before starting TheraSphere treatment. After 4 weeks Sorafenib therapy, Y-90 procedure performed. TheraSphere administered via infusion under imaging guidance through an hepatic arterial catheter appropriately positioned in the arterial anatomy to permit selective infusion of TheraSphere into the target tissue selected for treatment. The procedure should take about 1½ to 3 hours to complete.
Drug: Sorafenib
Starting dose 400 mg by mouth 2 times a day starting on Day 1 of Cycle 1, 4 weeks before starting TheraSphere treatment
Other Names:
  • Nexavar
  • BAY 43-9006
Radiation: Yttrium-90 Microspheres
After 4 weeks (+/- 1 week) of sorafenib therapy, Y-90 procedure performed. TheraSphere is administered via infusion under imaging guidance through an hepatic arterial catheter appropriately positioned in the arterial anatomy to permit selective infusion of TheraSphere into the target tissue selected for treatment.
Behavioral: Follow-Up Phone Calls
After completion of End-of-Treatment visit, study staff will contact participant by phone every 3 months. Each follow-up phone call should last about 15-30 minutes.

Primary Outcome Measures :
  1. Toxicity of Sorafenib and Yttrium-90 [ Time Frame: Start of treatment up to two 28-day cycles ]
    Toxicity is defined as any grade 3 or greater complications attributable to the treatment. Participants will be evaluated for toxicity every 4 weeks after start of study drug which may include the sorafenib treatment and Y-90 procedure since the Y-90 procedure may be performed (+/- 1 week) after start of sorafenib treatment.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. 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.
  2. Male or female patients ≥ 18 years of age
  3. Life expectancy of at least 12 weeks (3 months).
  4. Patients with histological or cytologically documented 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.
  5. 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).
  6. 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).
  7. 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.
  8. Patients who have received Yttrium-90 microspheres are not eligible.
  9. Patients who have an ECOG PS =/< 1.
  10. Patients who are categorized under BCLC-C stage.
  11. Cirrhosis grade of Child-Pugh class A. Child-Pugh status should be calculated based on clinical findings and laboratory results during the screening period.
  12. The following laboratory parameters: a) Platelet count =/> 60 x 10^9/L ; b) Hemoglobin =/> 8.5 g/dL; c) Total bilirubin =/< 2.5 mg/dl; d) Alanine transaminase (ALT) and Aspartate aminotransferase (AST) =/< 5 x upper limit of normal; e) Serum creatinine =/< 1.5 x the upper limit of normal.
  13. Prothrombin time (PT)-international normalized ratio (INR) =/< 2.3 or PT =/< 6 seconds above control.
  14. 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).
  15. 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.
  16. 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.
  17. Subject must be able to swallow and retain oral medication.

Exclusion Criteria:

  1. Main portal vein thrombosis (PVT)
  2. Patients who are eligible for curative treatment (ablation or resection or transplantation).
  3. 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.
  4. 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
  5. Contraindications to angiography and selective visceral arterial catheterization.
  6. 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.
  7. Concomitant treatment or within 28 days of one of the following: a) Any other systemic anticancer agent other than agents used for cancer prevention; b) Subjects who have used strong CYP3A4 inducers (eg, 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; c) UGT 1A1 and UGT 1A9 substrates (e.g., irinotecan); d) P-Gp substrates (e.g., Digoxin).
  8. Prior radiation therapy to the liver.
  9. Prior systemic therapy for the treatment of HCC, including sorafenib.
  10. Any history of symptomatic pulmonary compromise, such as chronic obstructive pulmonary disease.
  11. Any prior intervention for, or ongoing compromise of, the Ampulla of Vater or biliary-enteric anastomosis.
  12. Clinically evident ascites (trace ascites on imaging is acceptable).
  13. Pregnant or breast-feeding patients.
  14. A positive serum pregnancy test within 14 days prior to treatment in women of childbearing potential.
  15. Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm Hg [NCI-CTCAE v4.0] on repeated measurement) despite optimal medical management.
  16. Active or clinically significant cardiac disease including: a) Congestive heart failure - New York Heart Association (NYHA) > Class II; b) Active coronary artery disease; c) Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin; d) Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before treatment, or myocardial infarction within 6 months before treatment.
  17. Evidence or history of bleeding diathesis or uncontrolled coagulopathy.
  18. 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.
  19. Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) within 6 months of informed consent.
  20. Presence of a non-healing wound, non-healing ulcer, or bone fracture.
  21. History of organ allograft. (Including corneal transplant).
  22. 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.
  23. Any malabsorption condition.
  24. Inability to comply with the protocol and/or not willing or not available for follow-up assessments.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01900002

United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Principal Investigator: Ahmed Kaseb, MBBS M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT01900002     History of Changes
Other Study ID Numbers: 2012-0870
NCI-2013-01667 ( Registry Identifier: NCI CTRP )
First Posted: July 16, 2013    Key Record Dates
Last Update Posted: January 25, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Liver Cancer
Advanced Hepatocellular Carcinoma
BAY 43-9006
Phone calls

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Liver Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs