Cisplatin or Carboplatin and Sorafenib in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery
Condition: Liver Cancer
MeSH terms: Liver Neoplasms
Intervention: Carboplatin; Cisplatin; Sorafenib
Intervention description: Carboplatin AUC =6 at the investigator's discretion. Treatment is given every 6 weeks for up to 12 Cycles.; 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.; Sorafenib 400 mg po bid daily starting on Day 1 (± up to 3 days) continuously.
Intervention MeSH terms: Carboplatin; Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: adult primary hepatocellular carcinoma; localized unresectable adult primary liver cancer; advanced adult primary liver cancer

Summary:

      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.
    

Eligibility 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