Cisplatin or Carboplatin and Sorafenib in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00875615
First received: April 2, 2009
Last updated: November 11, 2013
Last verified: November 2013
  Purpose

RATIONALE: Drugs used in chemotherapy, such as cisplatin and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. Infusing chemotherapy directly into the liver and giving it together with sorafenib may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects of infusing cisplatin or carboplatin directly into the liver and giving it together with sorafenib in treating patients with liver cancer that cannot be removed by surgery.


Condition Intervention Phase
Liver Cancer
Drug: Carboplatin
Drug: Cisplatin
Drug: Sorafenib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Intrahepatic Artery Chemotherapy With Nexavar in Hepatocellular Carcinoma Patients

Resource links provided by NLM:


Further study details as provided by University of Miami Sylvester Comprehensive Cancer Center:

Primary Outcome Measures:
  • Number of Subjects Experiencing Adverse Events [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
    The number of subjects experiencing adverse events after receiving protocol therapy.


Secondary Outcome Measures:
  • Number of Patients Achieving Clinical Benefit [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    Number of patients achieving complete or partial response according to RECIST criteria


Enrollment: 11
Study Start Date: December 2008
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cisplatin or Carboplatin + Sorafenib Drug: Carboplatin
Carboplatin AUC =6 at the investigator's discretion. Treatment is given every 6 weeks for up to 12 Cycles.
Drug: Cisplatin
Cisplatin 60 m/m² via percutaneous intrahepatic (IA) artery infusion at the investigator's discretion. Treatment is given every 6 weeks for up to 12 Cycles.
Drug: Sorafenib
Sorafenib 400 mg po bid daily starting on Day 1 (± up to 3 days) continuously.

Detailed Description:

OBJECTIVES:

Primary

  • To assess the safety of intrahepatic arterial infusion of cisplatin or carboplatin in combination with sorafenib tosylate in patients with unresectable hepatocellular carcinoma.

Secondary

  • To assess the time to tumor progression in patients treated with this regimen.
  • To assess the overall and progression-free survival of patients treated with this regimen.

OUTLINE: Patients receive intrahepatic arterial infusion of cisplatin or carboplatin over 30-45 minutes on day 1 and oral sorafenib tosylate twice daily on days 8-35. Treatment repeats every 42 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed hepatocellular carcinoma (HCC) OR serum alpha fetoprotein ≥ 400 ng/mL with radiological evidence suggestive of HCC

    • Unresectable disease
  • Child-Pugh class A or selected Child-Pugh class B disease (Child-Pugh score ≤ 7 points)

    • No Child-Pugh class C disease
  • No disease outside the liver or macroscopic invasion of the major vessels such as the portal vein
  • No known brain metastasis

    • Patients with neurological symptoms must undergo CT scan or MRI of the brain

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • WBC ≥ 3,000/mm³ (for patients scheduled to receive carboplatin) or ≥ 2,000/mm³ (for patients scheduled to receive cisplatin)
  • Platelet count ≥ 100,000/mm³ (for patients scheduled to receive carboplatin) or ≥ 60,000/mm³ (for patients scheduled to receive cisplatin)
  • Serum creatinine ≤ 1.9 mg/dL (for patients scheduled to receive carboplatin) or ≤ 1.5 mg/dL (for patients scheduled to receive cisplatin)
  • Serum total bilirubin ≤ 3 mg/dL
  • AST and ALT < 5 times upper limit of normal
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
  • No cardiac disease, including any of the following:

    • NYHA class III-IV congestive heart failure
    • Unstable angina (anginal symptoms at rest)
    • New onset of angina within the past 3 months
    • Myocardial infarction within the past 6 months
    • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
  • No uncontrolled hypertension, defined as systolic 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 evidence or history of bleeding diathesis or coagulopathy
  • No evidence of encephalopathy
  • No condition that would impair the ability to swallow whole pills
  • No history of malabsorption problems
  • No significant traumatic injury within the past 4 weeks
  • No serious non-healing wound, ulcer, or bone fracture
  • No active clinically serious infection
  • No known HIV infection
  • No known or suspected allergy to sorafenib tosylate or any other study agent

PRIOR CONCURRENT THERAPY:

  • No prior cisplatin, carboplatin, or sorafenib tosylate
  • No prior systemic chemotherapy for HCC
  • No other prior systemic or locoregional therapy
  • More than 4 weeks since prior major surgery or open biopsy
  • No concurrent St. John's wort or rifampin
  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: NCT00875615

Locations
United States, Florida
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami Sylvester Comprehensive Cancer Center
Investigators
Principal Investigator: Lynn G. Feun, MD University of Miami Sylvester Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00875615     History of Changes
Other Study ID Numbers: UMIAMI-20080793, SCCC-2007101, BAYER-SCCC-2007101
Study First Received: April 2, 2009
Results First Received: July 18, 2013
Last Updated: November 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Miami Sylvester Comprehensive Cancer Center:
adult primary hepatocellular carcinoma
localized unresectable adult primary liver cancer
advanced adult primary liver cancer

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

ClinicalTrials.gov processed this record on July 23, 2014