Liver Cancer
Conditions
Keywords
adult primary hepatocellular carcinoma, localized unresectable adult primary liver cancer, advanced adult primary liver cancer, recurrent adult primary liver cancer
Brief summary
RATIONALE: Sunitinib 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. PURPOSE: This phase II trial is studying how well sunitinib works in treating patients with liver cancer that cannot be removed by surgery.
Detailed description
OBJECTIVES: Primary * Demonstrate the antitumor activity of continuous sunitinib malate treatment in patients with unresectable hepatocellular carcinoma. Secondary * Evaluate the safety of sunitinib malate treatment. * Measure serum cobalamin (i.e., vitamin B12) level during sunitinib malate treatment in order to investigate the relationship between sunitinib malate treatment and cobalamin deficiency. * Control the cobalamin deficiency by cobalamin replacement. * Investigate whether changes in tumor density could be used as a criterion for tumor response in future trials. OUTLINE: This is a multicenter study. Patients receive oral sunitinib malate once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on day 1 of each course to assess serum cobalamin levels and correlation with sunitinib malate treatment. Patients are also assessed for changes in tumor density and correlation with response. Baseline CT scans are compared with scans performed at 6 and 12 weeks to evaluate changes in CT-scan density due to tumor necrosis and response. After completion of study therapy, patients are followed at least every 3 months for up to 3 years.
Interventions
DRUGsunitinib malate
* Starting dose: 37.5 mg 3 x 12.5 mg capsule * Reduced dose: 25 mg 2 x 12.5 mg capsule
Sponsors
Swiss Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: Inclusion criteria: * Histologically, cytologically, or radiologically confirmed hepatocellular carcinoma (HCC) meeting 1 of the following criteria: * Localized, surgically unresectable disease * Candidates for radical surgery for locally advanced disease are excluded * Metastatic disease * Measurable disease, defined as ≥ 1 lesion, outside of pretreated areas, that can be measured in ≥ 1 dimension as ≥ 10 mm by spiral or multi-slice CT scan or MRI * Child-Pugh class A or mildly decompensated Child-Pugh class B liver dysfunction
Exclusion criteria
* Clinical ascites of any grade * Clinical symptoms or history of CNS metastases or leptomeningeal disease * Known fibrolamellar HCC or mixed cholangiocarcinoma and HCC PATIENT CHARACTERISTICS: Inclusion criteria: * WHO performance status 0-1 * Hemoglobin ≥ 9.0 g/dL * Absolute neutrophil count ≥ 1,500/mm³ * Platelet count ≥ 75,000/mm³ * Bilirubin ≤ 2 times upper limit of normal (ULN) * ALT ≤ 7 times ULN * Albumin ≥ 2.5 g/dL * Creatinine clearance ≥ 40 mL/min * Quick test ≥ 50% (adequate coagulation) * Urine dipstick for proteinuria \< 2+ OR ≤ 1 g of protein in 24-hour urine collection * Negative pregnancy test * Fertile patients must use effective contraception during and for 12 months after completion of study therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival | at 12 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Serum alpha fetoprotein level | Serum AFP levels will be measured during the therapy, if AFP is ≥ 1.5 x ULN at baseline. |
| Objective response | Objective response (CR+PR) to treatment will be determined. CR or PR is to be confirmed after a minimum of 4 weeks |
| Disease stabilization (DS) | Disease stabilization (CR, PR or SD) under sunitinib treatment will be determined |
| Adverse events as assessed by NCI CTCAE v3.0 | All AEs will be assessed according to NCI CTCAE v3.0. |
| Progression-free survival | PFS will be calculated from registration until documented tumor progression or death, whichever occurs first. |
| Time to progression | TTP will be calculated from registration until documented tumor progression or death due to tumor. |
| Overall survival | OS will be calculated from registration until death |
| Duration of DS | Duration of DS (CR, PR or SD) will be calculated from the time that measurement criteria are met for the first time until documented tumor progression |
Countries
Switzerland
Outcome results
None listed