Sorafenib Tosylate in Treating Patients With Liver Cancer That Can Be Removed by Surgery

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2010 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01182272
First received: August 13, 2010
Last updated: NA
Last verified: August 2010
History: No changes posted
  Purpose

RATIONALE: Sorafenib tosylate 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.

PURPOSE: This phase II trial is studying how well sorafenib tosylate works in treating patients with liver cancer that can be removed by surgery.


Condition Intervention Phase
Liver Cancer
Drug: sorafenib tosylate
Other: laboratory biomarker analysis
Procedure: neoadjuvant therapy
Procedure: therapeutic conventional surgery
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Proof-of-Concept Phase II Study to Evaluate the Anti-Tumor Activity of Sorafenib Along With Pathological and Molecular Changes in Tumor Samples From Patients With Resectable Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Antiangiogenic effects of sorafenib tosylate [ Designated as safety issue: No ]
  • Significant pathological changes [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pathologic findings in sorafenib tosylate pre-treated patients undergoing surgical resection for hepatocellular carcinoma [ Designated as safety issue: No ]
  • Number of R0 resections [ Designated as safety issue: No ]
  • Correlations between baseline patient characteristics, cancer biomarkers, and outcome variables and resected tumors [ Designated as safety issue: No ]
  • Plasma biomarkers at baseline, day 28, and the day before surgery [ Designated as safety issue: No ]
  • Safety profile of sorafenib tosylate [ Designated as safety issue: Yes ]
  • Tolerance of liver resection after sorafenib tosylate treatment [ Designated as safety issue: Yes ]

Estimated Enrollment: 36
Study Start Date: May 2010
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To assess anti-tumor activity of neoadjuvant sorafenib tosylate in tumor samples from patients with resectable hepatocellular carcinoma (HCC).

Secondary

  • To characterize pathologic findings in sorafenib tosylate pre-treated patients undergoing surgical resection for HCC: 1-2 core tumor biopsies will be performed prior to treatment and at day 35.
  • To evaluate the number of R0 resections in these patients.
  • To correlate pathological biomarker changes in resected tumors after 4-week treatment with sorafenib tosylate in comparison with biopsies obtained prior to treatment in these patients.
  • To evaluate plasma biomarkers, including PIGF, VEGF-A, VEGF-C, sVEGFR2, sVEGFR3, sKIT, IL-6, Ang2, IL-8, bFGF, AFP, collagen 4, endostatin, thrombospondin, TSP-1 and angiostatin, and CXCL12 at baseline, day 28, and the day before surgery.
  • To identify potential biomarkers of sensitivity and/or resistance on biological and pathological samples of these patients (exploratory).
  • To characterize the safety profile of sorafenib tosylate in these patients.
  • To assess the tolerance of liver resection after sorafenib tosylate treatment of these patients.

OUTLINE: This is a multicenter study.

Patients receive oral sorafenib tosylate twice daily on days 1-28 in the absence of unacceptable toxicity. Approximately 7 days after completion of sorafenib tosylate therapy, patients undergo liver resection.

Blood and tissue specimens are collected periodically for laboratory and biomarker assessments. Biomarkers include both molecular markers investigating the direct antitumor effects of sorafenib tosylate against cancer cells vs the effects of the drug on angiogenesis.

After completion of study treatment, patients are followed up on day 50 and at 3 months after surgery.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed hepatocellular carcinoma (HCC)

    • Fibrolamellar or mixed histology allowed
    • No cholangiocarcinoma or other tubal disease
  • Must be eligible for conservative hepatic resection or liver resection with curative intent
  • No cirrhosis with Child-Pugh score > 7
  • Chronic liver disease without liver insufficiency and without portal liver hypertension allowed
  • No known history or presence of metastatic brain or meningeal tumors

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Life expectancy ≥ 3 months
  • WBC > 3,000/µL
  • ANC > 1,500/µL
  • Platelet count ≥ 100,000/µL
  • Hemoglobin ≥ 9 g/dL
  • Bilirubin < 1.5 times upper normal limit (ULN)
  • AST and ALT ≤ 5 times UNL
  • Alkaline phosphatase ≤ 5 times ULN
  • Serum creatinine < 2 times ULN
  • PT/INR/PTT < 1.5 times UNL
  • Amylase and lipase < 1.5 times ULN
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Body mass index 18.5-30 kg/m^2 (WHO normal range: 18.5-25 kg/m^2)
  • Able to swallow oral compound
  • No criterion for unresectability or medical condition that contraindicates surgical resection
  • No serious concurrent systemic disorder incompatible with the study, including any of the following:

    • Uncontrolled hypertension (i.e., BP > 150/100 mm Hg despite optimal therapy)
    • Active uncontrolled infection
    • Active alcoholism
  • No prior medical disorder, including any of the following:

    • Cardiac arrhythmias requiring anti-arrhythmics (excluding beta-blockers or digoxin for chronic atrial fibrillation)
    • Active coronary artery disease or ischemia
    • Myocardial infarction within the past 6 months
    • NYHA class III-IV congestive heart failure
    • Pulmonary embolism within the past 6 months
    • Gastrointestinal bleeding within the past 6 months
  • No other prior malignancy within the past 5 years, except basal cell or squamous cell skin carcinoma or cured in situ cervical carcinoma
  • No history or concurrent seizure disorder requiring medications (e.g., antiepileptic drugs)
  • No history of HIV infection, or chronic hepatitis B or C
  • No active clinically serious bacterial or fungal infection (i.e., grade 2 CTCAE v. 3)
  • No condition that is unstable or could jeopardize the safety of the patient and his/her compliance with the study
  • No substance abuse or medical, psychological, or social condition that could interfere with adherence to the study
  • No known or suspected allergy to the investigational agent or to any agent given concurrently
  • No presence of asthenia or rash > CTC grade 1 at enrollment
  • Must be registered in a national health-care system

PRIOR CONCURRENT THERAPY:

  • No prior orthotopic liver transplantation
  • Not a candidate for orthotopic liver transplantation
  • No prior systemic or loco-regional treatment for HCC
  • No prior organ allograft
  • No treatment with any other investigational medicinal product within the past 28 days
  • No concurrent treatment with full-dose anticoagulants

    • Deep-vein or catheter-associated thrombosis prophylaxis allowed
    • Warfarin or heparin therapy allowed if the coagulation parameters were within the acceptable ranges prior to initiation of anticoagulant therapy
  • No concurrent or chronic co-administration of CYP3A4 inducers (e.g., rifampin, Hypericum perforatum, phenytoin, carbamazepine, phenobarbital, or dexamethasone)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01182272

Locations
France
Hopital Beaujon Recruiting
Clichy, France, 92110
Contact: Contact Person    33-1-4087-5614    sandrine.faivre@bjn.aphp.fr   
Sponsors and Collaborators
Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
Investigators
Principal Investigator: Sandrine Faivre Hopital Beaujon
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT01182272     History of Changes
Other Study ID Numbers: CDR0000682840, FRE-GERCOR-D09-1-BIOSHARE, EUDRACT-2009-018058-44, EU-21058
Study First Received: August 13, 2010
Last Updated: August 13, 2010
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
adult primary hepatocellular carcinoma
localized resectable adult primary liver cancer

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Liver Neoplasms
Adenocarcinoma
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Niacinamide
Sorafenib
Antineoplastic Agents
Enzyme Inhibitors
Growth Substances
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses
Vitamin B Complex
Vitamins

ClinicalTrials.gov processed this record on October 21, 2014