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

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)

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.

Study Overview

• Status: Completed
• Conditions: Liver Cancer
• Intervention / Treatment: Drug: Placebo; Procedure: transarterial chemoembolization; Drug: sunitinib malate

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.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Amiens, France
    • CHU Nord
  • Annecy, France
    • CHR
  • Avignon, France
    • Institut Sainte Catherine
  • Besancon, France
    • CHU J Minjoz
  • Bordeaux, France
    • Institut Bergonie
  • Béziers, France
    • CH
  • Caen, France
    • CHU côte de Nacre
  • Clermont Ferrand, France
    • CHU
  • Cornebarrieu, France
    • Clinique des Cèdres
  • Dijon, France
    • CHU Bocage
  • Guilherand Granges, France
    • CH
  • Lille, France, 59037
    • Hôpital Claude Huriez
  • Limoges, France
    • Hôpital Dupuytren
  • Lorient, France
    • CHBS
  • Lyon, France
    • Hopital Prive Jean Mermoz
  • Marseille, France
    • CHU La Timone
  • Marseille, France
    • Hopital Saint Joseph
  • Marseille, France
    • CH Ambroise Paré
  • Marseille, France
    • CH Conception
  • Montpellier, France
    • CHRU Saint Eloi
  • Nice, France
    • CHU -Hôpital de l'Archet II
  • Orléans, France
    • CHR
  • Paris, France, 75970
    • Hôpital Tenon
  • Paris, France
    • Hôpital Européen Georges Pompidou
  • Paris, France
    • Groupe Hospitalier Paris St Joseph
  • Poitiers, France
    • CHU Jean Bernard
  • Reims, France
    • CHU Robert Debré
  • Rennes, France
    • CAC
  • Rouen, France
    • CHU
  • Tours, France
    • CHU
  • Villejuif, France
    • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; placebo 3cps/days 4 weeks over 6 during 1 year	Drug: Placebo; placebo 3cps/days 4 weeks over 6 during 1 year; Procedure: transarterial chemoembolization; Chimioembolisation
EXPERIMENTAL: Sunitinib; 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	Procedure: transarterial chemoembolization; Chimioembolisation; Drug: sunitinib malate; placebo 3cps/days 4 weeks over 6 during 1 year

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Federation Francophone de Cancerologie Digestive
• Investigators: Principal Investigator: Mohamed Hebbar, MD, Centre Hospital Universitaire Hop Huriez

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (ACTUAL): July 1, 2017
• Study Completion (ACTUAL): July 1, 2017

Study Registration Dates

• First Submitted: July 15, 2010
• First Submitted That Met QC Criteria: July 15, 2010
• First Posted (ESTIMATE): July 16, 2010

Study Record Updates

• Last Update Posted (ACTUAL): March 18, 2022
• Last Update Submitted That Met QC Criteria: March 17, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: advanced adult primary liver cancer; localized unresectable adult primary liver cancer; adult primary hepatocellular carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: PRODIGE 16; FFCD-PRODIGE-16; FFCD-0905; EUDRACT-2009-017064-16; EU-21050