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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.

Phase 2
18 Years
Not Enrolling
Hepatocellular Carcinoma, Fibrolamellar Hepatocellular Carcinoma

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Trial Information

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
was available).

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.

Inclusion Criteria:

- Fibrolamellar hepatocellular carcinoma histopathologically proven

- Inoperable/advanced (Tumor recurrence inoperable or metastatic with no surgical

- Available Tumor tissue for analysis(biopsy or surgical specimen)

- Performance status WHO ≤ 2.

- Adequate organ function :

- Hematology (absolute neutrophil count equal or superior to 1,5 x 10*9/l ,
platelet equal or superior to 100 x 10*9/l),

- clearance of creatinine > 60 ml/min),

- AST/ALT ≤ 5 N, PAL ≤ 5 N, total bilirubin ≤ 2N.

Exclusion Criteria:

- Hypersensitivity to sunitinib.

- Contraindication to sunitinib, including uncontrolled hypertension, medical history
of cerebrovascular accident, unstable cardiac pathology despite optimal medical
therapy (myocardial infarction within the 6 months prior to study drug
administration, severe/unstable angina ), active hemorrhagic syndrome or concomitant
treatment with anticoagulants.

- Any severe acute or chronic co-morbid that may compromise to comply with study
participation : uncontrolled infection, symptomatic congestive heart failure, liver
disturbance, chronic renal failure, active gastro-duodenal ulcer (nonexhaustive list)

- Known brain metastases.

- Diagnosis of any second malignancy within the last 3 years, except for basal cell or
squamous cell skin cancer, or in situ carcinoma of the cervix uteri

- Current treatment on another clinical trial.

- Prior treatment with an investigational agent within 4 weeks

- Patient on i.v bisphosphonate therapy

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective response

Outcome Description:

to evaluate the objective response according to RECIST Criteria 1.1

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Sandrine Faivre, Professor

Investigator Role:

Principal Investigator

Investigator Affiliation:

Assistance Publique - Hôpitaux de Paris


France: Ministry of Health

Study ID:




Start Date:

October 2009

Completion Date:

May 2012

Related Keywords:

  • Hepatocellular Carcinoma
  • Fibrolamellar Hepatocellular Carcinoma
  • Carcinoma, Hepatocellular
  • Carcinoma
  • Fibrosis
  • Liver Neoplasms
  • Pathologic Processes
  • Digestive System Neoplasms
  • Neoplasms by Site
  • Neoplasms
  • Liver Diseases
  • Adenocarcinoma
  • Neoplasms, Glandular and Epithelial
  • Neoplasms by Histologic Type
  • Sunitinib
  • Antineoplastic Agents
  • Therapeutic Uses
  • Pharmacologic Actions
  • Angiogenesis Inhibitors
  • Angiogenesis Modulating Agents
  • Growth Substances
  • Physiological Effects of Drugs
  • Growth Inhibitors
  • Carcinoma
  • Carcinoma, Hepatocellular