Clinical trial NCT01164202: Chemoembolization of the Liver With or Without Sunitinib Malate in Treating Patients With Liver Cancer
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Liver Cancer
Keywords: adult primary hepatocellular carcinoma
localized unresectable adult primary liver cancer
advanced adult primary liver cancer
Lead sponsor: Federation Francophone de Cancerologie Digestive
Sponsor class: OTHER
First posted: 2010-07-16
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Patients With Occurrence of Severe Bleeding and/or Liver Failure
timeFrame: Up to 7 days following each TACE, up to 5 months of treatment
Secondary outcomes:
measure: Overall Survival
timeFrame: From randomization until death or last news for alive patients, up to 3 years
measure: Disease-free Survival
timeFrame: From randomization until the date of first progression (clinical or radiological) or death from any cause whichever came first
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Nord
city: Annecy
country: France
facility: CHR
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Besancon
country: France
facility: CHU J Minjoz
city: Bordeaux
country: France
facility: Institut Bergonié
city: Béziers
country: France
facility: CH
city: Caen
country: France
facility: CHU Côte de Nacre
city: Clermont Ferrand
country: France
facility: CHU
city: Cornebarrieu
country: France
facility: Clinique des Cèdres
city: Dijon
country: France
facility: CHU Bocage
city: Guilherand Granges
country: France
facility: CH
city: Lille
country: France
facility: Hôpital Claude Huriez
city: Limoges
country: France
facility: Hopital Dupuytren
city: Lorient
country: France
facility: CHBS
city: Lyon
country: France
facility: Hôpital Privé Jean Mermoz
city: Marseille
country: France
facility: CH Ambroise Paré
city: Marseille
country: France
facility: CH Conception
city: Marseille
country: France
facility: CHU La Timone
city: Marseille
country: France
facility: Hôpital Saint Joseph
city: Montpellier
country: France
facility: CHRU Saint Eloi
city: Nice
country: France
facility: CHU -Hôpital de l'Archet II
city: Orléans
country: France
facility: CHR
city: Paris
country: France
facility: Hopital Tenon
city: Paris
country: France
facility: Groupe Hospitalier Paris St Joseph
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Poitiers
country: France
facility: CHU Jean Bernard
city: Reims
country: France
facility: CHU Robert Debré
city: Rennes
country: France
facility: CAC
city: Rouen
country: France
facility: CHU
city: Tours
country: France
facility: CHU
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Centre Hospital Universitaire Hop Huriez
name: Mohamed Hebbar, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Turpin A, de Baere T, Heurgue A, Le Malicot K, Ollivier-Hourmand I, Lecomte T, Perrier H, Vergniol J, Sefrioui D, Rinaldi Y, Edeline J, Jouve JL, Silvain C, Becouarn Y, Dauvois B, Baconnier M, Debette-Gratien M, Deplanque G, Dharancy S, Lepage C, Hebbar M; PRODIGE 16 investigators Collaborators. Liver transarterial chemoembolization and sunitinib for unresectable hepatocellular carcinoma: Results of the PRODIGE 16 study. Clin Res Hepatol Gastroenterol. 2021 Mar;45(2):101464. doi: 10.1016/j.clinre.2020.05.012. Epub 2020 Jun 21.