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Study of Sunitinib in Patients With Advanced/Inoperable Fibrolamellar Carcinoma (Fibrolam)

Primary Purpose

Hepatocellular Carcinoma, Fibrolamellar Hepatocellular Carcinoma

Status
Terminated
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Sutent
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hôpital Beaujon

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

patient treated

Arm Description

patient who receive sunitinib

Outcomes

Primary Outcome Measures

Objective response
to evaluate the objective response according to RECIST Criteria 1.1

Secondary Outcome Measures

Objective response
to evaluate objective response to sunitinib according to secondary radiological criteria (evaluation on CT scan of: tumor density, % of tumor necrosis and tumor vascularisation)
Overall survival
Progression-Free survival
Biomarkers of response
to evaluate the correlation between biomarkers expression and objective response so sunitinib
Biomarkers of radiological response
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

Full Information

First Posted
September 24, 2010
Last Updated
March 12, 2014
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT01215565
Brief Title
Study of Sunitinib in Patients With Advanced/Inoperable Fibrolamellar Carcinoma
Acronym
Fibrolam
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.
Study Type
Interventional

2. Study Status

Record Verification Date
March 2014
Overall Recruitment Status
Terminated
Why Stopped
lack of inclusion
Study Start Date
October 2009 (undefined)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
May 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma, Fibrolamellar Hepatocellular Carcinoma
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
patient treated
Arm Type
Experimental
Arm Description
patient who receive sunitinib
Intervention Type
Drug
Intervention Name(s)
Sutent
Intervention Description
Sunitinib 50mg/day (per os) for 6 cycles duration of one cycle = 6 weeks (4 weeks of treatment over 6 weeks)
Primary Outcome Measure Information:
Title
Objective response
Description
to evaluate the objective response according to RECIST Criteria 1.1
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Objective response
Description
to evaluate objective response to sunitinib according to secondary radiological criteria (evaluation on CT scan of: tumor density, % of tumor necrosis and tumor vascularisation)
Time Frame
1 year
Title
Overall survival
Time Frame
6 months and 1 year
Title
Progression-Free survival
Time Frame
6 months and 1 year
Title
Biomarkers of response
Description
to evaluate the correlation between biomarkers expression and objective response so sunitinib
Time Frame
1 year
Title
Biomarkers of radiological response
Description
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
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sandrine Faivre, Professor
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Beaujon
City
Clichy
State/Province
Hauts de Seine
ZIP/Postal Code
92110
Country
France

12. IPD Sharing Statement

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Study of Sunitinib in Patients With Advanced/Inoperable Fibrolamellar Carcinoma

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