Chemoembolization of the Liver With or Without Sunitinib Malate in Treating Patients With Liver Cancer

Study Overview
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Brief Summary
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RATIONALE: Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping anticancer drugs near the tumor. Sunitinib malate 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. It is not yet known whether chemoembolization is more effective with or without sunitinib malate in treating patients with liver cancer. PURPOSE: This randomized phase II/III trial is studying the side effects of chemoembolization of the liver and to see how well in works when given together with or without sunitinib malate in treating patients with liver cancer.

Detailed Description
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OBJECTIVES: Primary To evaluate unacceptable bleeding or hepatic failure at 10 weeks post-treatment in patients with unresectable hepatocellular carcinoma treated with transarterial chemoembolization in combination with sunitinib malate versus transarterial chemoembolization alone. To evaluate the overall survival of these patients. Secondary To evaluate the tumor stabilization rate in these patients. To evaluate the safety of this regimen in these patients. To evaluate the disease-free survival of these patients. To evaluate the relapse-free survival of these patients. To evaluate the quality of life of these patients. To evaluate the overall survival rate at 2 years of these patients. OUTLINE: This is a multicenter study. Pilot: Patients receive oral sunitinib malate once daily on days 1-28. Beginning 7-10 days later, patients undergo 1-3 courses of transarterial chemoembolization (TACE). Treatment repeats every 6 weeks for 1 year. Randomization: Patients are stratified according to main tumor diameter (< 5 cm vs ≥ 5 cm), nodular involvement (uninodular vs multinodular), and center. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive sunitinib malate and TACE as in the pilot phase. Arm II: Patients receive oral placebo once daily on days 1-28 and TACE as in the pilot phase. Quality of life is assessed periodically.

Official Title
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A Double-Blind, Randomized, Phase II/III Study Comparing the Use of Chemoembolization Combined With Sunitinib Against Chemoembolization Combined With a Placebo in Patients With Hepatocellular Carcinoma (SATURNE)

Conditions
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Liver Cancer

Intervention / Treatment
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* Drug: sunitinib malate
* Drug: Placebo
* Procedure: transarterial chemoembolization


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed hepatocellular carcinoma or liver tumor responding to the Barcelona criteria Child-Pugh score of 5-6 (Class A) Tumor suitable for transarterial chemoembolization (one or more planned courses allowed) Tumor not suitable for surgical resection No extrahepatic metastases, including cerebral metastases PATIENT CHARACTERISTICS: ECOG performance status 0-2 Absolute neutrophil count ≥ 1.5 x 10^9/L Platelet count ≥ 100 x 10^9/L Hemoglobin ≥ 10 g/dL PT ≥ 50% Creatinine ≤ 120 μmol/L Bilirubin normal ALT/AST ≤ 3.5 times upper limit of normal (ULN) Alkaline phosphatases ≤ 4 times ULN Fibrinogen ≥ 1.5 g/L Not pregnant or nursing Fertile patients must use effective contraception No portal vein thrombosis Able to comply with scheduled follow-up and management of toxicity No uncontrolled hypertension or requiring ≥ 2 classes of antihypertensive drugs No concomitant disease or uncontrolled severe disease No contraindications to the vascular occlusion procedure No prior or concurrent malignancy within the past 5 years, except adequately treated cone-biopsied carcinoma in situ of the cervix or basal cell carcinoma of the skin No psychiatric disability or social, family, or geographic reason for which the patient may not be followed regularly PRIOR CONCURRENT THERAPY: At least 7 days since prior CYP3A4 inhibitors or inducers At least 3 months since prior radiofrequency ablation No prior chemotherapy No prior sunitinib, sorafenib, or any other inhibitors of angiogenesis No concurrent participation in another trial

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>placebo 3cps/days 4 weeks over 6 during 1 year | Drug: Placebo<br>* placebo 3cps/days 4 weeks over 6 during 1 year<br>Procedure: transarterial chemoembolization<br>* Chimioembolisation<br>|
| Experimental: Sunitinib<br>sunitinib (SUTENT®) 37,5 mg/d (3 cps of 12,5 mg) orally 4 weeks over 6 (4 weeks of treatment followed by 2 weeks without treatment) during 1 year | Drug: sunitinib malate<br>* placebo 3cps/days 4 weeks over 6 during 1 year<br>Procedure: transarterial chemoembolization<br>* Chimioembolisation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Occurrence of Severe Bleeding and/or Liver Failure | The number of patients with at least one bleed and/or liver failure by treatment group | Up to 7 days following each TACE, up to 5 months of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival is defined as the time from the date of randomization to the date of death (from any cause). Patients lost to follow-up or alive at the time of analysis are censored at the last news date or the point date. This time is used to calculate the median follow-up time. | From randomization until death or last news for alive patients, up to 3 years | 
| Disease-free Survival | Disease-free survival is defined as the time interval between randomization and local or distant relapse or second cancer or death (all causes). Alive patients are censored at the last follow-up. | From randomization until the date of first progression (clinical or radiological) or death from any cause whichever came first | 

 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