Sorafenib Tosylate Before and After Hepatic Arterial Chemoembolization With Doxorubicin Hydrochloride and Mitomycin C in Treating Patients With Localized Liver Cancer That Cannot Be Removed by Surgery

NCT00949182 | Completed Phase 2

• 3 other identifiers: CDR0000649008UMDNJ-20090859BAYER-IST000477
• Study Type: interventional
• Target: 20
• 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 and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as doxorubicin hydrochloride and mitomycin C, 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 blood flow to the tumor. Giving sorafenib tosylate before and after chemoembolization may kill more tumor cells. PURPOSE: This phase II trial is studying the side effects and how well giving sorafenib tosylate before and after hepatic arterial chemoembolization with doxorubicin hydrochloride and mitomycin C works in treating patients with localized liver cancer that cannot be removed by surgery.

Conditions

Liver Cancer

Keywords

localized unresectable adult primary liver cancer; adult primary hepatocellular carcinoma

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability as assessed by NCI CTCAE v3.0

  06/2009 to 12/2010

Secondary Outcomes (4)

• Number of hepatic arterial chemoembolization (HACE) treatments required to achieve objective complete response

  06/2009 to 12/2010

• Progression-free survival and time to radiologic progression as assessed by CT scan

  06/2009 to 12/2010

• Overall survival at 6, 12, and 24 months

  06/2009 to 12/2011

• AFP and VEGF serum levels as assessed at baseline, prior to each HACE treatment, and then every 3 months thereafter

  06/2009 to 12/2011

Study Arms (1)

Sorafenib Tosylate, Doxorubicin, Mytomicin C

EXPERIMENTAL

Micro and Macro arteriolar blockade of hepatocellular carcinoma (HCC): Treatment with Sorafenib 400mg two weeks prior to embolization HACE which includes the use of agents such as Doxorubicin Hydrochloride and Mytomicin C, continuing same Sorafenib dose after the procedure (dose adjustment according to tolerance).

Drug: sorafenib tosylate, HACE : Doxorubicin Hydrochloride and Mitomycin C; Other: laboratory biomarker analysis

Interventions

sorafenib tosylate, HACE : Doxorubicin Hydrochloride and Mitomycin C DRUG

After Sorafenib Tosylate has been administered the actual HACE procedure is performed using Doxorubicin Hydrochloride or Mitomycin C

Also known as: Doxorubicin brand name Adriamycin.

Sorafenib Tosylate, Doxorubicin, Mytomicin C

laboratory biomarker analysis OTHER

Sorafenib Tosylate, Doxorubicin, Mytomicin C

Eligibility Criteria

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

You may qualify if:

• Age \> 18 years old
• Confirmed HCC diagnosis by Biopsy or Radiologic parameters. Following NCCN guidelines for HACE, including subjects within the University of San Francisco transplant listing criteria.
• ECOG Performance Status 0 or 1
• Adequate bone marrow, liver and renal function as .assessed by the following:
• Hemoglobin \> 9.0 g/dl
• Absolute neutrophil count (ANC) \> 1,500/mm3
• Platelet count \> 75,000/mm3
• Total bilirubin \< 2 mg/dl
• ALT and AST \< 2.5 times the ULN ( \< 5 x ULN for patients with liver involvement)
• Creatinine \< 1.5 times mg/dl
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
• Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least three months after the last administration of sorafenib.
• Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
• INR \< 1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
• BCLC Stage B (Intermediate)

You may not qualify if:

• Cardiac disease: Congestive heart failure \> class II NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
• Known brain metastasis or CNS disease. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• Uncontrolled hypertension defined as systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management.
• Known human immunodeficiency virus (HIV) infection
• Active clinically serious infection \> CTCAE Grade 2 except hepatitis B or C.
• Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
• Pulmonary hemorrhage/bleeding event \> CTCAE Grade 2 within 4 weeks of first dose of study drug.
• Any other hemorrhage/bleeding event \> CTCAE Grade 3 within 4 weeks of first dose of study drug.
• Serious non-healing wound, ulcer, or bone fracture.
• Evidence or history of bleeding diathesis or coagulopathy
• Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
• Use of St. John's Wort or rifampin (rifampicin).
• Known or suspected allergy to sorafenib or any agent given in the course of this trial.
• Any condition that impairs patient's ability to swallow whole pills.

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead

Study Sites (1)

Rutgers University Hospital

Newark, New Jersey, 07101, United States

Location

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular

Interventions

Sorafenib; Mitomycin

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; Mitomycins; Indolequinones; Quinones; Azirines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Andrew N. de la Torre, MD

  Rutgers University Hospital / St Joseph Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D

Study Record Dates

• First Submitted: July 29, 2009
• First Posted: July 30, 2009
• Study Start: July 1, 2009
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: January 14, 2014

Record last verified: 2014-01

Locations

US (1)