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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase II Trial of Intrahepatic Artery Chemotherapy With Nexavar in Hepatocellular Carcinoma Patients

Conditions
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Liver Cancer

Intervention / Treatment
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* Drug: Carboplatin
* Drug: Cisplatin
* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cisplatin or Carboplatin + Sorafenib<br> | Drug: Carboplatin<br>* Carboplatin AUC =6 at the investigator's discretion. Treatment is given every 6 weeks for up to 12 Cycles.<br>Drug: Cisplatin<br>* 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.<br>Drug: Sorafenib<br>* Sorafenib 400 mg po bid daily starting on Day 1 (± up to 3 days) continuously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Experiencing Adverse Events | The number of subjects experiencing adverse events after receiving protocol therapy. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Achieving Clinical Benefit | Number of patients achieving complete or partial response according to RECIST criteria | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult primary hepatocellular carcinoma, localized unresectable adult primary liver cancer, advanced adult primary liver cancer