A Multicenter National Phase II Open Study Coupled With Translational Assessment of Biomarkers Predictive of Response to Sunitinib in Patients With Advanced/Inoperable Fibrolamellar Hepatocellular Carcinoma.
Fibrolamellar hepatocellular carcinoma is variant rare of hepatocellular carcinoma witch
distinct clinical, histological and prognostic features from conventional hepatocellular
carcinoma. This entity typically occurs in young adults with no underlying hepatitis or
cirrhosis. Surgical resections could be proposed in some referral centers and this in cases
of localized tumors. However, in cases of postoperative recurrence, "salvage" resection is
not often possible. Overall prognosis remains poor, because of its primary chemoresistance
and early recurrence of metastasis.
Sunitinib (SUTENT) is a potent tyrosine kinase inhibitor, with double antiangiogenic and
antitumor activity, targeting multiple receptors as VEGF-R, PDGF-R, KIT and FLT3.
Since 2006, Sunitinib has been approved to treat advanced kidney cancer also called advanced
renal cell carcinoma (a typically chemoresistant disease for which there no active treatment
Several targets of sunitinib are overexpressed hepatocellular carcinoma lines as shown in
the Literature review and pathological studies.
Otherwise, the overexpression of PDGFR and VEGFR correlates with recurrence and invasion in
HCC. Finally, sunitinib showed an interesting antitumor activity in patients with
conventional advanced HCC.
Thereby, it seems important to study how well the sunitinib, a potent antitumor and
antiangiogenic agent, works in treating patients with advanced or inoperable fibrolamellar
hepatocellular carcinoma especially, this setting lacks effective therapies. Furthermore, it
seems urgent to conduct translational research and assessment to identify predictive
biomarkers of response.
In this study, orally sunitinib at dosed of 50 mg daily will be administrated to patients
for 4 weeks, followed by 2 weeks of wash out. This administration schedule is based on the
phase I study of sunitinib.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
to evaluate the objective response according to RECIST Criteria 1.1
Sandrine Faivre, Professor
Assistance Publique - Hôpitaux de Paris
France: Ministry of Health