Chemoembolization With or Without Sorafenib Tosylate in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery

This study is currently recruiting participants.
Verified April 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01004978
First received: October 29, 2009
Last updated: April 9, 2014
Last verified: April 2014

October 29, 2009
April 9, 2014
October 2009
February 2018   (final data collection date for primary outcome measure)
Progression-free survival [ Time Frame: Time from randomization to progression or death without evidence of progression, assessed up to 4 years ] [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01004978 on ClinicalTrials.gov Archive Site
  • Overall survival [ Time Frame: Time from randomization to death from any cause, or last known date of survival, assessed up to 4 years ] [ Designated as safety issue: No ]
  • Incidence of adverse events, graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]
  • Overall survival [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Chemoembolization With or Without Sorafenib Tosylate in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery
A Phase III Randomized, Double-Blind Trial of Chemoembolization With or Without Sorafenib in Unresectable Hepatocellular Carcinoma (HCC) in Patients With and Without Vascular Invasion

This randomized phase III trial is studying chemoembolization and sorafenib tosylate to see how well they work compared with chemoembolization alone in treating patients with liver cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as doxorubicin hydrochloride, mitomycin, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Chemoembolization kills tumor cells by carrying drugs directly into the tumor and blocking the blood flow to the tumor. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving chemoembolization together with sorafenib tosylate is more effective than chemoembolization alone in treating patients with liver cancer.

PRIMARY OBJECTIVE:

I. To compare Progression-Free Survival (PFS) of chemoembolization alone to sorafenib in combination with chemoembolization.

SECONDARY OBJECTIVES:

I. To compare overall survival (OS) of chemoembolization alone to sorafenib in combination with chemoembolization.

II. To evaluate extra-hepatic versus intra-hepatic patterns of failure. III. To determine the rates of toxicity related to Sorafenib in combination with chemoembolization.

TERTIARY OBJECTIVES:

I. To analyze the pharmacogenetic and pharmacokinetic properties of Sorafenib including angiogenesis, monooxygenases, polymorphisms and MDR.

II. ECOG secondary imaging objective: Site vs. Central evaluation of PFS. III. To determine the inter-reader concordance for response characterization at four and eight months by the European Association for the Study of Liver (EASL) criteria.

IV. To determine the value of objective tumor response at four and eight months by the EASL criteria to predict PFS (by RECIST) and OS.

V. To evaluate the effects of intra-hepatic vs. extra-hepatic progression on OS.

OUTLINE: This is a multicenter study. Patients are stratified according to macrovascular intrahepatic portal vein invasion (present vs absent), Child Pugh score (A vs B7), and chemoembolization method (doxorubicin-eluting bead vs conventional). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive sorafenib tosylate orally (PO) twice daily in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of sorafenib tosylate is reached, patients undergo transarterial chemoembolization (TACE) comprising doxorubicin hydrochloride, mitomycin C, and cisplatin (closed to accrual as of 10/1/2010); conventional chemoembolization comprising doxorubicin hydrochloride only; or chemoembolization comprising doxorubicin-eluting beads. Treatment with TACE repeats approximately every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo PO twice daily in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of placebo is reached, patients undergo TACE as in arm I.

MAINTENANCE THERAPY: After completion of chemoembolization, patients receive sorafenib tosylate or placebo as in arm I and II in the absence of disease progression or unacceptable toxicity. Patients undergo chest, abdomen, and/or pelvis CT scans or MRI at baseline, at 4 and 8 months, and every 2 months thereafter.

Blood and tissue samples may be collected at baseline and periodically during study for pharmacogenetic and pharmacokinetic studies. After completion of study therapy, patients are followed up periodically for 4 years.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Adult Primary Hepatocellular Carcinoma
  • Localized Unresectable Adult Primary Liver Cancer
  • Recurrent Adult Primary Liver Cancer
  • Drug: sorafenib tosylate
    Given PO
    Other Names:
    • BAY 43-9006
    • BAY 43-9006 Tosylate Salt
    • BAY 54-9085
    • Nexavar
    • SFN
  • Other: placebo
    Given PO
    Other Name: PLCB
  • Drug: doxorubicin hydrochloride
    Undergo TACE
    Other Names:
    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF
  • Drug: doxorubicin-eluting beads
    Undergo TACE
  • Drug: cisplatin
    Undergo TACE
    Other Names:
    • CACP
    • CDDP
    • CPDD
    • DDP
  • Drug: mitomycin C
    Undergo TACE
    Other Names:
    • MITC
    • MITO
    • MITO-C
    • Mitocin-C
    • MTC
  • Experimental: Arm I (sorafenib tosylate and TACE)
    Patients receive sorafenib tosylate PO twice daily in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of sorafenib tosylate is reached, patients undergo TACE comprising doxorubicin hydrochloride, mitomycin C, and cisplatin (closed to accrual as of 10/1/2010); conventional chemoembolization comprising doxorubicin hydrochloride only; or chemoembolization comprising doxorubicin-eluting beads. Treatment with TACE repeats approximately every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: sorafenib tosylate
    • Drug: doxorubicin hydrochloride
    • Drug: doxorubicin-eluting beads
    • Drug: cisplatin
    • Drug: mitomycin C
  • Placebo Comparator: Arm II (placebo and TACE)
    Patients receive placebo PO twice daily in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of placebo is reached, patients undergo TACE as in arm I.
    Interventions:
    • Other: placebo
    • Drug: doxorubicin hydrochloride
    • Drug: doxorubicin-eluting beads
    • Drug: cisplatin
    • Drug: mitomycin C
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
400
Not Provided
February 2018   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of hepatocellular carcinoma (HCC) according to 1 of the following criteria:

    • Histologically confirmed disease
    • Liver cirrhosis AND ≥ 1 solid liver lesion > 2 cm with early enhancement and delayed enhancement washout on CT scan or MRI regardless of alpha-fetoprotein levels (AFP)
    • AFP > 400 ng/mL AND ≥ 1 solid liver lesion > 2 cm regardless of specific imaging characteristics on CT scan or MRI
  • Disease must be limited to the liver

    • No clinical or radiographic evidence of extra hepatic HCC
    • Portal vein lymphadenopathy is allowed for patients with hepatitis B or C
  • Branch portal vein invasion by tumor allowed

    • No main portal vein invasion by tumor
  • Measurable disease constituting < 50% of liver parenchyma within the past 4 weeks
  • Child Pugh score of A or B7 within the past 4 weeks
  • No ascites detectable on physical evaluation
  • Not a candidate for curative resection, orthotopic liver transplantation, or radiofrequency ablation (RFA)
  • ECOG performance status 0-1
  • Life expectancy ≥ 3 months
  • Platelet count ≥ 50,000/μL
  • Total bilirubin ≤ 2.0 mg/dL
  • Alkaline phosphatase < 5 times upper limit of normal (ULN)
  • AST and ALT < 5 times ULN
  • Serum creatinine ≤ 1.5 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Able to swallow pills
  • No clinical signs of heart failure
  • No NYHA class III or IV heart disease
  • No evidence of bleeding diathesis or active gastrointestinal bleeding
  • No known HIV positivity
  • No other concurrent uncontrolled illness (except hepatitis B or C) including, but not limited to, any of the following:

    • Uncontrolled hypertension (i.e., optimally treated baseline BP > 150/90 mm Hg)
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness and/or addictive disorder that would limit compliance with study requirements
  • No allergy to iodine or gadolinium contrast that cannot be safely controlled with premedication
  • No prior brachytherapy (e.g., yttrium-90 microspheres)
  • No prior sorafenib tosylate, chemoembolization, or systemic chemotherapy, including cytotoxic agents or molecularly targeted agents
  • Prior attempted curative liver resection allowed
  • More than 4 weeks since prior RFA
  • No concurrent cytochrome P450 enzyme-inducing drugs
  • No concurrent prophylactic G-CSF or GM-CSF
Both
18 Years and older
No
Not Provided
United States
 
NCT01004978
NCI-2011-01981, NCI-2011-01981, ECOG-E1208, CDR0000657952, E1208, E1208, U10CA021115
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: John Kauh Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP