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

NCT ID: NCT01164202

Last Updated: 2022-03-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2017-07-31

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.

Conditions

Liver Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

placebo 3cps/days 4 weeks over 6 during 1 year

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo 3cps/days 4 weeks over 6 during 1 year

transarterial chemoembolization

Intervention Type: PROCEDURE

Chimioembolisation

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

Group Type: EXPERIMENTAL

sunitinib malate

Intervention Type: DRUG

placebo 3cps/days 4 weeks over 6 during 1 year

transarterial chemoembolization

Intervention Type: PROCEDURE

Chimioembolisation

Interventions

sunitinib malate

placebo 3cps/days 4 weeks over 6 during 1 year

Intervention Type: DRUG

Placebo

placebo 3cps/days 4 weeks over 6 during 1 year

Intervention Type: DRUG

transarterial chemoembolization

Chimioembolisation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federation Francophone de Cancerologie Digestive

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mohamed Hebbar, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospital Universitaire Hop Huriez

Locations

CHU Nord

Amiens, , France

CHR

Annecy, , France

Institut Sainte Catherine

Avignon, , France

CHU J Minjoz

Besançon, , France

CH

Béziers, , France

Institut Bergonié

Bordeaux, , France

CHU Côte de Nacre

Caen, , France

CHU

Clermont-Ferrand, , France

Clinique des Cèdres

Cornebarrieu, , France

CHU Bocage

Dijon, , France

CH

Guilherand-Granges, , France

Hôpital Claude Huriez

Lille, , France

Hopital Dupuytren

Limoges, , France

CHBS

Lorient, , France

Hôpital Privé Jean Mermoz

Lyon, , France

CH Ambroise Paré

Marseille, , France

CH Conception

Marseille, , France

CHU La Timone

Marseille, , France

Hôpital Saint Joseph

Marseille, , France

CHRU Saint Eloi

Montpellier, , France

CHU -Hôpital de l'Archet II

Nice, , France

CHR

Orléans, , France

Hopital Tenon

Paris, , France

Groupe Hospitalier Paris St Joseph

Paris, , France

Hôpital Européen Georges Pompidou

Paris, , France

CHU Jean Bernard

Poitiers, , France

CHU Robert Debré

Reims, , France

CAC

Rennes, , France

CHU

Rouen, , France

CHU

Tours, , France

Institut Gustave Roussy

Villejuif, , France

Countries

France

References

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.

Reference Type: RESULT

PMID: 32576496 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

FFCD-PRODIGE-16

Identifier Type: -

Identifier Source: secondary_id

FFCD-0905

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2009-017064-16

Identifier Type: -

Identifier Source: secondary_id

EU-21050

Identifier Type: -

Identifier Source: secondary_id

PRODIGE 16

Identifier Type: -

Identifier Source: org_study_id