- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01215565
Study of Sunitinib in Patients With Advanced/Inoperable Fibrolamellar Carcinoma (Fibrolam)
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.
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
Study Overview
Status
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Hauts de Seine
-
Clichy, Hauts de Seine, France, 92110
- Hopital Beaujon
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: patient treated
patient who receive sunitinib
|
Sunitinib 50mg/day (per os) for 6 cycles duration of one cycle = 6 weeks (4 weeks of treatment over 6 weeks)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response
Time Frame: 1 year
|
to evaluate the objective response according to RECIST Criteria 1.1
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response
Time Frame: 1 year
|
to evaluate objective response to sunitinib according to secondary radiological criteria (evaluation on CT scan of: tumor density, % of tumor necrosis and tumor vascularisation)
|
1 year
|
Overall survival
Time Frame: 6 months and 1 year
|
6 months and 1 year
|
|
Progression-Free survival
Time Frame: 6 months and 1 year
|
6 months and 1 year
|
|
Biomarkers of response
Time Frame: 1 year
|
to evaluate the correlation between biomarkers expression and objective response so sunitinib
|
1 year
|
Biomarkers of radiological response
Time Frame: 1 year
|
to evaluate the correlation between biomarkers expression and secondary radiological criteria (significant decrease of tumor density on CT scan, formation of significant intratumor necrosis, significant decrease of tumoral vascularisation using of perfusion software
|
1 year
|
Collaborators and Investigators
Investigators
- Principal Investigator: Sandrine Faivre, Professor, Assistance Publique - Hôpitaux de Paris
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- Fibrosis
- Pathologic Processes
- Carcinoma
- Neoplasms
- Adenocarcinoma
- Antineoplastic Agents
- Liver Diseases
- Physiological Effects of Drugs
- Carcinoma, Hepatocellular
- Liver Neoplasms
- Pharmacologic Actions
- Therapeutic Uses
- Neoplasms, Glandular and Epithelial
- Neoplasms by Histologic Type
- Neoplasms by Site
- Digestive System Neoplasms
- Sunitinib
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Digestive System Neoplasms
- Liver Diseases
- Liver Neoplasms
- Carcinoma
- Carcinoma, Hepatocellular
- 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
- P070134
- 2008-003423-23 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Hepatocellular Carcinoma
-
Roswell Park Cancer InstituteNational Comprehensive Cancer NetworkCompletedAdvanced Adult Hepatocellular Carcinoma | Localized Non-Resectable Adult Hepatocellular Carcinoma | Stage IIIA Hepatocellular Carcinoma | Stage IIIB Hepatocellular Carcinoma | Stage IIIC Hepatocellular Carcinoma | Stage IVA Hepatocellular Carcinoma | Stage IVB Hepatocellular Carcinoma | Stage III... and other conditionsUnited States
-
Academic and Community Cancer Research UnitedNational Cancer Institute (NCI)RecruitingUnresectable Hepatocellular Carcinoma | Stage III Hepatocellular Carcinoma AJCC v8 | Stage IIIA Hepatocellular Carcinoma AJCC v8 | Stage IV Hepatocellular Carcinoma AJCC v8 | Stage IVA Hepatocellular Carcinoma AJCC v8 | Stage IVB Hepatocellular Carcinoma AJCC v8 | BCLC Stage B Hepatocellular Carcinoma and other conditionsUnited States
-
Roswell Park Cancer InstituteMerck Sharp & Dohme LLCActive, not recruitingAdvanced Adult Hepatocellular Carcinoma | Child-Pugh Class A | Stage III Hepatocellular Carcinoma | Stage IIIA Hepatocellular Carcinoma | Stage IIIB Hepatocellular Carcinoma | Stage IIIC Hepatocellular Carcinoma | Stage IV Hepatocellular Carcinoma | Stage IVA Hepatocellular Carcinoma | Stage IVB Hepatocellular...United States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedUnresectable Hepatocellular Carcinoma | Advanced Adult Hepatocellular Carcinoma | Stage IIIB Hepatocellular Carcinoma AJCC v7 | Stage IIIC Hepatocellular Carcinoma AJCC v7 | BCLC Stage C Hepatocellular Carcinoma | Stage IV Hepatocellular Carcinoma AJCC v7 | Stage III Hepatocellular Carcinoma AJCC... and other conditionsUnited States
-
Academic and Community Cancer Research UnitedNational Cancer Institute (NCI); Genentech, Inc.RecruitingUnresectable Hepatocellular Carcinoma | Stage III Hepatocellular Carcinoma AJCC v8 | Stage IIIA Hepatocellular Carcinoma AJCC v8 | Stage IV Hepatocellular Carcinoma AJCC v8 | Stage IVA Hepatocellular Carcinoma AJCC v8 | Stage IVB Hepatocellular Carcinoma AJCC v8 | Stage IIIB Hepatocellular Carcinoma... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedUnresectable Hepatocellular Carcinoma | Advanced Adult Hepatocellular Carcinoma | Recurrent Hepatocellular Carcinoma | Stage IIIB Hepatocellular Carcinoma AJCC v7 | Stage IIIC Hepatocellular Carcinoma AJCC v7 | Stage IV Hepatocellular Carcinoma AJCC v7 | Stage III Hepatocellular Carcinoma AJCC v7 and other conditionsUnited States, Canada, Puerto Rico
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingUnresectable Hepatocellular Carcinoma | Stage III Hepatocellular Carcinoma AJCC v8 | Stage IIIA Hepatocellular Carcinoma AJCC v8 | Stage IV Hepatocellular Carcinoma AJCC v8 | Stage IVA Hepatocellular Carcinoma AJCC v8 | Stage IVB Hepatocellular Carcinoma AJCC v8 | BCLC Stage B Hepatocellular Carcinoma and other conditionsUnited States
-
Mayo ClinicNational Cancer Institute (NCI)RecruitingAdvanced Hepatocellular Carcinoma | BCLC Stage B Hepatocellular Carcinoma | BCLC Stage C Hepatocellular Carcinoma | Metastatic Hepatocellular Carcinoma | BCLC Stage A Hepatocellular CarcinomaUnited States
-
Northwestern UniversityBristol-Myers Squibb; National Cancer Institute (NCI)CompletedStage IIIA Hepatocellular Carcinoma | Stage IIIB Hepatocellular Carcinoma | Stage IIIC Hepatocellular Carcinoma | Stage IVA Hepatocellular Carcinoma | Stage IVB Hepatocellular CarcinomaUnited States
-
Edward KimBristol-Myers Squibb; National Cancer Institute (NCI)TerminatedUnresectable Hepatocellular Carcinoma | Stage III Hepatocellular Carcinoma AJCC v8 | Stage IIIA Hepatocellular Carcinoma AJCC v8 | Stage IV Hepatocellular Carcinoma AJCC v8 | Stage IVA Hepatocellular Carcinoma AJCC v8 | Stage IVB Hepatocellular Carcinoma AJCC v8 | Stage IIIB Hepatocellular Carcinoma... and other conditionsUnited States
Clinical Trials on Sutent
-
Third Military Medical UniversityUnknownNon-small Cell Lung CancerChina
-
University Health Network, TorontoPfizerTerminated
-
PfizerTerminated
-
AGO Study GroupPhilipps University Marburg Medical Center; HSK Reasearch GmbH WiesbadenCompletedPlatinum Refractory Epithelial Ovarian Cancer | Primary Cancer of the Peritoneum | Cancer of the Fallopian TubeGermany
-
Daniel George, MDNovartis; PfizerCompletedRenal Cell CarcinomaUnited States
-
PfizerCompletedBreast NeoplasmsBelgium, Sweden, Italy
-
Icahn School of Medicine at Mount SinaiPfizerCompleted
-
Mothaffar RimawiTerminated
-
JLLC NatiVitaNational Anti Doping Laboratory, BelarusNot yet recruiting
-
Gilead SciencesCompletedHepatitis CUnited States, Australia, New Zealand, Puerto Rico