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

NCT01900002 | Completed Phase 2 Results

• 4 other identifiers: 2012-0870NCI-2013-01667Y-90P30CA016672
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Advanced Adult Hepatocellular Carcinoma; BCLC Stage C Hepatocellular Carcinoma; Recurrent Adult Hepatocellular Carcinoma; Stage III Hepatocellular Carcinoma AJCC v7; Stage IIIA Hepatocellular Carcinoma AJCC v7; Stage IIIB Hepatocellular Carcinoma AJCC v7; Stage IIIC Hepatocellular Carcinoma AJCC v7; Stage IV Hepatocellular Carcinoma AJCC v7; Stage IVA Hepatocellular Carcinoma AJCC v7; Stage IVB Hepatocellular Carcinoma AJCC v7; Unresectable Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (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).

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

Secondary Outcomes (2)

• Median Time to Progression (TTP)

  Up to 4 years

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

  Up to 4 years

Study Arms (1)

Treatment (sorafenib tosylate, TheraSphere)

EXPERIMENTAL

Patients 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.

Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Drug: Sorafenib; Drug: Sorafenib Tosylate; Radiation: Yttrium Y 90 Glass Microspheres

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (sorafenib tosylate, TheraSphere)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (sorafenib tosylate, TheraSphere)

Sorafenib DRUG

Given PO

Also known as: BAY 43-9006

Treatment (sorafenib tosylate, TheraSphere)

Sorafenib Tosylate DRUG

Given PO

Also known as: BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib

Treatment (sorafenib tosylate, TheraSphere)

Yttrium Y 90 Glass Microspheres RADIATION

Given IA

Also known as: TheraSphere

Treatment (sorafenib tosylate, TheraSphere)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 34527608 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dr. Ahmed Kaseb, MD, Professor, GI Medical Oncology
• Organization: UT MD Anderson Cancer Center

akaseb@mdanderson.org

(713) 792-2828

Study Officials

• Ahmed O Kaseb

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2013
• First Posted: July 16, 2013
• Study Start: September 13, 2013
• Primary Completion: December 10, 2020
• Study Completion: December 10, 2020
• Last Updated: December 30, 2021
• Results First Posted: December 30, 2021

Record last verified: 2021-12

Locations

US (1)