Sorafenib Tosylate and Chemoembolization in Treating Patients With Unresectable Liver Cancer

NCT01042041 | Completed Phase 1 DMC

• 2 other identifiers: UPCC 08208NCI-2009-01488
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs near the tumor. PURPOSE: This phase I trial is studying side effects and best dose of sorafenib tosylate when given together with chemoembolization in treating patients with unresectable liver cancer.

Conditions

Hepatocellular Carcinoma; Liver Cancer; Localized Unresectable Liver Cancer

Outcome Measures

Primary Outcomes (1)

• Dose adjustment, number and percentage of subjects with adverse events, laboratory changes, number and percentage of subjects with laboratory values that are outside the pre-determined ranges, cumulative toxicity, and TLT.

  8 months

Secondary Outcomes (1)

• Time to Disease Progression

  8 months

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive oral sorafenib tosylate twice daily. Beginning 2 weeks later, patients undergo chemoembolization with cisplatin, doxorubicin hydrochloride, and mitomycin C. Chemoembolization repeats once a month for up to 4 procedures in the absence of disease progression or unacceptable toxicity.

Drug: sorafenib tosylate; Drug: doxorubicin hydrochloride; Drug: cisplatin; Drug: mitomycin C; Procedure: transarterial chemoembolization; Procedure: hepatic artery embolization

Interventions

sorafenib tosylate DRUG

Given orally

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

Arm I

doxorubicin hydrochloride DRUG

Given via transarterial/hepatic chemoembolization

Also known as: ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF, Adriblastina

Arm I

cisplatin DRUG

Given via transarterial/hepatic chemoembolization

Also known as: CACP, CDDP, CPDD, DDP, Neoplatin, PDD

Arm I

mitomycin C DRUG

Given via transarterial/hepatic chemoembolization

Also known as: MITC, MITO, MITO-C, Mito-Medac, Mitocin-C, MTC

Arm I

transarterial chemoembolization PROCEDURE

Also known as: TACE

Arm I

hepatic artery embolization PROCEDURE

Arm I

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed hepatocellular carcinoma
• AND/OR Magnetic Resonance Imaging (MRI) or Computerized Tomography (CT) consistent with liver cirrhosis AND at least one solid liver lesion \> 2cm with arterial-phase enhancement and delayed washout regardless of alpha-feto protein levels (AFP)
• AND/OR AFP \> 400ng/mL AND evidence of at least one solid liver lesion \> 2cm regardless of specific imaging characteristics on CT or MRI
• Patient is not a candidate for transplantation, resection, or ablation; for whom the intended therapy is chemoembolization
• Patient meets clinical criteria for treatment with chemoembolization
• Absolute contraindications to chemoembolization include an uncorrectable bleeding disorder, uncorrectable contrast sensitivity, leukopenia (white blood cell count \< 1000/uL), cardiac or renal insufficiency (serum creatinine \> 2.0mg/dL), hepatic encephalopathy, jaundice, or dilated intrahepatic bile ducts
• Portal vein occlusion is a relative contraindication and chemoembolization can be performed only if there are collateral vessels with hepato-pedal flow demonstrated angiographically
• Hepatic compromise as determined by the following combination of parameters is a contraindication to therapy: lactate dehydrogenase \> 425 U/L, aspartate aminotransferase \> 100 U/L, total bilirubin \> 2.0 mg/dL and \> 50% liver volume replaced by tumor
• Patients may have been treated with ablation or resection in the past, but no sooner than 4 weeks before study registration
• Patients may NOT have been previously treated with sorafenib, chemoembolization, radioembolization, or systemic chemotherapy with cytotoxic agents or molecularly targeted agents
• ECOG performance status =\< 2
• Life expectancy of greater than 3 months
• Platelets \>= 50,000/mcL
• Total bilirubin =\< 2.0 mg/dl
• AST(SGOT)/ALT(SGPT) =\< 3X institutional upper limit of normal

You may not qualify if:

• Patients may not be receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib
• History of radiologic contrast reactions not controlled by standard premedications
• Patients must not be taking cytochrome P450 enzyme inducing drugs
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study
• Breastfeeding should be discontinued
• Prophylactic use of G-CSF or GM-CSF is not permitted on this trial

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abramson Cancer Center of The University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

Sorafenib; Doxorubicin; Cisplatin; Mitomycin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; 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; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Mitomycins; Indolequinones; Quinones; Azirines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Michael Soulen

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 10, 2009
• First Posted: January 5, 2010
• Study Start: September 1, 2009
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: February 26, 2013

Record last verified: 2013-02

Locations

US (1)