Sorafenib in Treating Patients With Locally Advanced or Metastatic Liver Cancer and Cirrhosis

NCT00767468 | Terminated Phase 1 DMC

• 4 other identifiers: LCCC 0717P30CA016086CDR0000615311BAYER-UNC-LCCC-0717
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This phase I trial is studying the side effects and best dose of sorafenib in treating patients with locally advanced or metastatic liver cancer and cirrhosis.

Conditions

Liver Cancer

Keywords

adult primary hepatocellular carcinoma; advanced adult primary liver cancer; localized unresectable adult primary liver cancer; recurrent adult primary liver cancer

Outcome Measures

Primary Outcomes (1)

• Correlation between hepatic retention and clearance of technetium Tc 99m mebrofenin (MEB) and technetium Tc 99m sestamibi (MIBI) and clearance (and other pharmacokinetic parameters) of sorafenib tosylate

  4 years

Secondary Outcomes (8)

• Tolerable dose of sorafenib tosylate

  4 years

• Correlation between the pharmacokinetics of MEB and MIBI and the dose-limiting toxicity of sorafenib tosylate

  4 years

• Conjugated or unconjugated bilirubin increase in response to sorafenib tosylate

  4 years

• Correlation between increased bilirubin and decreased clearance of MEB and/or MIBI

  4 years

• Correlation between survival and MRI characteristics associated with high tumor VEGF levels

  4 years

Study Arms (2)

Bilirubin Normal to 3x Upper Limit of Normal

EXPERIMENTAL

Drug: sorafenib tosylate

Bilirubin >3x to 6x Upper Limit of Normal

EXPERIMENTAL

Drug: sorafenib tosylate

Interventions

sorafenib tosylate DRUG

Sorafenib 400mg BID until disease progression or patient withdrawal.

Also known as: Sorafenib, Nexavar

Bilirubin >3x to 6x Upper Limit of Normal; Bilirubin Normal to 3x Upper Limit of Normal

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Diagnosis of hepatocellular carcinoma (HCC) according to tissue histology\* NOTE: \*Recurrence of previously resected HCC does not require tissue confirmation if there is clear radiographic recurrence, in the opinion of the investigator * Locally advanced or metastatic disease OR not eligible for surgical resection or immediate liver transplantation * Child-Pugh class B cirrhosis * Moderate hepatic dysfunction (bilirubin ≤ 3 times upper limit of normal \[ULN\]) OR severe hepatic dysfunction (bilirubin \> 3 times but ≤ 6 times ULN) * No known brain metastasis unless the metastasis has been stable for \> 3 months PATIENT CHARACTERISTICS: * ECOG performance status 0-1 * Life expectancy \> 12 weeks * Hemoglobin \> 9.0 g/dL * ANC \> 1,000/mm\^3 * Platelet count \> 45,000/mm\^3 * ALT and AST \< 7 times ULN * INR \< 2.0 * Creatinine \< 1.7 times ULN OR creatinine clearance \> 50 mL/min * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for ≥ 2 weeks after completion of study treatment * No history of uncontrolled seizures, CNS disorders, or psychiatric disability that, in the opinion of the investigator, is clinically significant, precludes giving informed consent, or interferes with compliance of oral drug intake * No other concurrent active malignancy * No active clinically serious infection \> CTCAE grade 2 * No known hypersensitivity to sorafenib tosylate or to any of the excipients * No known or suspected allergy to sorafenib tosylate or to any agent given in the course of this study * No NYHA class III or IV congestive heart failure * No unstable angina * No new onset angina (i.e., within the past 3 months) * No myocardial infarction within the past 6 months * No cardiac ventricular arrhythmias requiring anti-arrhythmic therapy * No uncontrolled hypertension, defined as systolic blood pressure (BP) \> 150 mm Hg or diastolic BP \> 90 mm Hg, despite optimal medical management * No thrombolic or embolic events (e.g., cerebrovascular accident, including transient ischemic attacks) within the past 6 months * No pulmonary hemorrhage/bleeding event \> CTCAE grade 2 within the past 4 weeks * No other hemorrhage/bleeding event \> CTCAE grade 3 within the past 4 weeks * No variceal bleeding within the past 90 days * No known grade 2 or 3 esophageal varices * No evidence or history of bleeding diathesis or coagulopathy * No significant traumatic injury within the past 4 weeks * No serious non-healing wound, ulcer, or bone fracture * No other serious uncontrolled medical condition (e.g., uncontrolled ascites or encephalopathy) that, in the opinion of the investigator, may compromise study participation * No condition that would impair the patient's ability to swallow whole pills * No malabsorption problem * No active drug or alcohol abuse PRIOR CONCURRENT THERAPY: * No more than one prior therapy including, but not limited to, any of the following: * Systemic chemotherapy * Hepatic artery infusion of chemotherapy * Chemoembolization * Radioembolization * Ablation * At least 4 weeks since prior embolization, resection, or ablation * No prior RAF/MEK/ERK-targeting therapy or VEGF-targeting therapy * More than 4 weeks since prior participation in an investigational drug study * More than 4 weeks since prior major surgery or open biopsy * No concurrent chronic anticoagulation other than 1 mg of warfarin per day for central venous catheter patency * No concurrent St. John's wort or rifampin

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599-7295, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

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

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

Study Officials

• Bert H. O'Neil, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2008
• First Posted: October 7, 2008
• Study Start: October 1, 2008
• Primary Completion: February 1, 2010
• Study Completion: November 1, 2010
• Last Updated: May 23, 2012

Record last verified: 2012-05

Locations

US (2)