Study of Sunitinib in Patients With Advanced/Inoperable Fibrolamellar Carcinoma

Brief Title

Study of Sunitinib in Patients With Advanced/Inoperable Fibrolamellar Carcinoma

Official Title

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.

Brief Summary

      The purpose of this study is to evaluate the antitumor activity of sunitinib in patients with
      advanced/inoperable fibrolamellar hepatocellular carcinoma.

      Rationale: Sunitinib 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
    

Detailed Description

      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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Objective response

Secondary Outcome

 Objective response

Condition

Hepatocellular Carcinoma

Intervention

Sutent

Study Arms / Comparison Groups

 patient treated
Description:  patient who receive sunitinib

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

4

Start Date

October 2009

Completion Date

May 2012

Primary Completion Date

May 2011

Eligibility Criteria

        Inclusion Criteria:

          -  Fibrolamellar hepatocellular carcinoma histopathologically proven

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

          -  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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Sandrine Faivre, Professor, , 

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT01215565

Organization ID

P070134

Secondary IDs

2008-003423-23

Responsible Party

Sponsor

Study Sponsor

Assistance Publique - Hôpitaux de Paris


Study Sponsor

Sandrine Faivre, Professor, Principal Investigator, Assistance Publique - Hôpitaux de Paris


Verification Date

March 2014