Sorafenib Tosylate and Chemoembolization in Treating Patients With Unresectable Liver Cancer

This study has been completed.
Sponsor:
Information provided by:
Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01042041
First received: December 10, 2009
Last updated: February 25, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Hepatocellular Carcinoma
Liver Cancer
Localized Unresectable Liver Cancer
Drug: sorafenib tosylate
Drug: doxorubicin hydrochloride
Drug: cisplatin
Drug: mitomycin C
Procedure: transarterial chemoembolization
Procedure: hepatic artery embolization
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of Sorafenib Integrated With Chemoembolization for Patients With Unresectable Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by Abramson Cancer Center of the University of Pennsylvania:

Primary Outcome Measures:
  • 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. [ Time Frame: 8 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to Disease Progression [ Time Frame: 8 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: September 2009
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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
Given orally
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Drug: doxorubicin hydrochloride
Given via transarterial/hepatic chemoembolization
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
  • Adriblastina
Drug: cisplatin
Given via transarterial/hepatic chemoembolization
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
  • Neoplatin
  • PDD
Drug: mitomycin C
Given via transarterial/hepatic chemoembolization
Other Names:
  • MITC
  • MITO
  • MITO-C
  • Mito-Medac
  • Mitocin-C
  • MTC
Procedure: transarterial chemoembolization
Other Name: TACE
Procedure: hepatic artery embolization

Detailed Description:

PRIMARY OBJECTIVE:

I. To evaluate the toxicity and safety of integrating sorafenib with chemoembolization for unresectable hepatocellular carcinoma.

SECONDARY OBJECTIVE:

I. To observe the imaging response (AASLD/EASL modification of RECIST) and time to progression following chemoembolization in conjunction with sorafenib.

OUTLINE:

Patients receive oral sorafenib tosylate twice daily. Beginning 2 weeks later, patients undergo chemoembolization with cisplatin, doxorubicin hydrochloride, and mitomycin C.

Chemoembolizaton repeats once a month for up to 4 procedures in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 4 weeks and then every 3 months.

  Eligibility

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

Inclusion

  • 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
  • Creatinine =< 1.5 mg/dl
  • INR =< 1.5
  • Patients must have no clinical signs of heart failure and meet New York Heart Association functional classification I or II defined as:

Class I - Patients with no limitation of activities; they suffer no symptoms from ordinary activities; Class II - Patients with slight, mild limitation of activity; they are comfortable with rest or with mild exertion

  • Because agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
  • Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion

  • 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
  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: NCT01042041

Locations
United States, Pennsylvania
Abramson Cancer Center of The University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Abramson Cancer Center of the University of Pennsylvania
Investigators
Principal Investigator: Michael Soulen Abramson Cancer Center of the University of Pennsylvania
  More Information

No publications provided

Responsible Party: Soulen, Michael, Abramson Cancer Center of The University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01042041     History of Changes
Other Study ID Numbers: UPCC 08208, NCI-2009-01488
Study First Received: December 10, 2009
Last Updated: February 25, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Carcinoma
Liver Neoplasms
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Mitomycins
Mitomycin
Doxorubicin
Sorafenib
Cisplatin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Alkylating Agents
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014