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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01900002
First received: July 11, 2013
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Liver Cancer
Drug: Sorafenib
Radiation: Yttrium-90 Microspheres
Behavioral: Follow-Up Phone Calls
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Toxicity of Sorafenib and Yttrium-90 [ Time Frame: After 2, 28 day cycles ] [ Designated as safety issue: Yes ]
    Toxicity is defined as any grade 3 or greater complications attributable to the treatment.


Estimated Enrollment: 20
Study Start Date: September 2013
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 (+/- 1 week) of 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 of sorafenib: 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 patient by phone every 3 months. Each follow-up phone call should last about 15-30 minutes.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01900002

Contacts
Contact: Ahmed Kaseb, MBBS 713-792-2828

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

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01900002     History of Changes
Other Study ID Numbers: 2012-0870, NCI-2013-01667
Study First Received: July 11, 2013
Last Updated: May 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Liver Cancer
Advanced Hepatocellular Carcinoma
HCC
Sorafenib
Nexavar
BAY 43-9006
Yttrium-90
Microspheres
Phone calls

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Liver Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 15, 2014