Clinical trial NCT00875615: Cisplatin or Carboplatin and Sorafenib in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery
Official title: Phase II Trial of Intrahepatic Artery Chemotherapy With Nexavar in Hepatocellular Carcinoma Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Liver Cancer
Keywords: adult primary hepatocellular carcinoma
localized unresectable adult primary liver cancer
advanced adult primary liver cancer
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2009-04-03
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Number of Subjects Experiencing Adverse Events
timeFrame: 36 months
Secondary outcomes:
measure: Number of Patients Achieving Clinical Benefit
timeFrame: 36 months
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center - Miami
state: Florida
Study officials:
affiliation: University of Miami Sylvester Comprehensive Cancer Center
name: Lynn G. Feun, MD
role: PRINCIPAL_INVESTIGATOR
References: