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Study Summary
No. 2008-0396:.......Liver......Jean-Nicolas Vauthey......Surgical Oncology
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Study Summary Title
Study Summary
Number:
2008-0396
Study Title:A Phase III randomized, double-blind, placebo controlled study of sorafenib as adjuvant treatment for hepatocellular carcinoma after surgical resection or local ablation
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Physician New Patient Referral
Name:Jean-Nicolas VautheyPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Surgical OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-6940
Contact us about clinical trials
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General Information
Disease Group:LiverSupported By:Bayer Healthcare AG
Phase of Study:Phase IIIReturn
Visit:
Patients must return at week 4, week 8, week 12, week 16, week 20, week 24 and
then every 12 weeks until disease recurrence.
Treatment
Agents:
SorafenibHome Care:N/A
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
Standard for HCC resection or ablation surgery.
Description/
Intervention:
The goal of this clinical research study is to compare the benefits of
sorafenib to no treatment in patients who have recently had surgery or ablation
to remove liver cancer.
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Study Objectives / Outcomes
Objective:
To evaluate efficacy and safety of sorafenib versus placebo in the adjuvant treatment of Hepatocellular carcinoma (HCC) after potentially curative treatment with surgical resection or local ablation.

Primary efficacy objective: Recurrence Free Survival (RFS).

Secondary efficacy objective: Time to Recurrence (TTR). Overall Survival (OS).

Other objectives:
Patient-Reported Outcome (PRO) as assessed by FACT-Hep and EQ-5D questionnaire.
Evaluation of biomarkers.
Evaluation of pharmacokinetics
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Study Status Information
Study Activation / Registration Date:09/10/2009
IRB Review and Approval Date:09/10/2009
Study Type:Phase Iii
Recruitment Status:Closed
Projected Accrual:1100
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Informed consent must be obtained prior to commencing any study procedure

2) Confirmation of diagnosis of HCC for subjects undergoing a) surgical resection histological confirmation is mandatory (a post surgery pathology report is required for both histological confirmation and risk stratification); b) local ablation either histological confirmation of clinical diagnosis by AASLD criteria in cirrhotic subjects is required. For subjects without cirrhosis histological confirmation is mandatory

3) Confirmation of diagnosis of hepatocellular carcinoma prior to curative treatment, confirmation of a maximum tumor load of: a) single lesion any size for surgical resection, or single lesion less than or equal to 5cm (largest diameter, unidimensional measurement) for local ablation; b) 2-3 lesions, each less than or equal to 3cm in size (largest diameter, undimensional measurement)

4) Patients who have undergone surgical resection or local ablation (PEI or percutaneous or intraoperative RFA) for treatment of hepatocellular carcinoma with curative intent within 4 months from staging to potentially curative treatment (resection/ablation). A maximum of 2 local ablation courses may be administered during this time period (if the patient has had ablation for curative treatment, then no more than 2 local ablation courses may be performed)

5) Patients may have undergone resection or last local ablation course 4 weeks (28 days +/- 7 days) , to CT/MRI scan date (post curative treatment)

6) Male or female subjects greater than or equal to 18 years of age

7) Confirmation of complete response (CR) (absence of residual tumor after curative treatment), on the eligibility scan by independent radiological review

8) For subjects undergoing surgical resection pathologically clear margins proven complete removal of tumor

9) Intermediate Risk (single tumors 2-3cm in size, longest diameter, unidimensional measure) or High Risk (single tumors greater than 3-5 cm in size or 2 or 3 lesions each less than or equal to 3 cm in size) of recurrence as assessed by tumor characteristics.

10) Child-Pugh score 5-7 points. A Child-Pugh score of 7 points is allowed only in the absence of ascites

11) ECOG Performance Status of 0

12) Adequate bone marrow, liver and renal function as assessed by central lab by means of the following laboratory requirements from samples within 14 days of randomization a)Hemoglobin greater than of equal to 9.0g/dl b)Absolute neutrophil count (ANC) greater than or equal to 1,500/mm(3)Adequate bone marrow, liver and renal function as assessed by central lab by means of the following laboratory requirements from samples approximately 14 days prior to screening a)Hemoglobin greater than of equal to 9.0g/dl b)Absolute neutrophil count (ANC) greater than or equal to 1,500/mm(3)

13) CONTINUED FROM INCLUSION 12 - c) Platelet count greater than or equal to 50,000/ul d) Total bilirubin less than or equal to 2 mg/dL e) ALT and AST less than or equal to 5 times ULN f)Alkaline phosphatase less than or equal to 4 times ULN g) PT greater than 50% or PT-INR less than 2.3, or less than 6 seconds above control h) For subjects on warfarin, close monitoring of at least weekly evaluations will be performed until INR is stable based on a measurement at pre dose, as defined by the local standard of care i) Serum creatinine less than or equal to 1.5 x ULN

14) Women of childbearing potential must have a negative serum pregnancy test performed within 14 days prior to the start of treatment (assessed centrally)

15) Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and two weeks after the completion of trial

16) At least 3 weeks (21 days) but not more than 7 weeks (49 days) from resection or last local ablation course, to CT/MRI scan date. A timeframe of 4 weeks after surgical resection or last ablation is recommended

Exclusion Criteria:1) Recurrent hepatocellular carcinoma

2) Child-Pugh score 7 points with presence of ascites

3) The following tumor characteristics; a) low risk of recurrence after curative treatment defined as any of the following, for local ablation patients: single lesions less than 2 cm; for surgical resection patients: single lesions less than 2 cm without microscopic vascular invasion, without tumor satellites and histologically well differentiated b) greater than lesions or 2-3 lesions of which any are greater that 3 cm in size (largest diameter, unidimensional measurement) prior curative treatment (surgical resection or local ablation)

4) CONTINUED FROM CRITERIA 3 - c) single lesion greater than 5 cm (largest diameter, unidimensional measurement) in size prior local ablation d) Macrovascular invasion e) extrahepatic spread (including regional lymph nodes and invasion into adjacent structures)

5) History of cardiovascular disease; a) congestive heart failure greater than NYHA class 2 b) active CAD (MI more than 6 months prior to study entry is allowed) cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) c) uncontrolled hypertension with blood pressure >/= 140/90

6) History of HIV infection

7) Active clinically serious infections (greater than grade 2 NCI-CTCAE)

8) Subjects with seizure disorder requiring medication (such as steroids or anti-epileptics)

9) History of organ allograft

10) Subjects with evidence of history of bleeding diathesis

11) Subjects undergoing renal dialysis

12) Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated less than 3 years prior to study entry as defined by the signing of informed consent.

13) Uncontrolled ascites (defined as not easily controlled with diuretic treatment )

14) Encephalopathy

15) History of GI bleeding within 30 days of randomization

16) Subjects with a history of esophageal varices bleeding which has not been followed by effective therapy and/or treatment to prevent bleeding recurrence

17) Prior anti cancer therapy for treatment of HCC (including sorafenib or any other molecular therapy) is excluded.

18) Major surgery within 4 weeks of start of study (as defined by signing of informed consent), except for surgical resection or local ablation of hepatocellular carcinoma.

19) Autologous bone marrow transplant or stem cell rescue within 4 months of study as defined by signing of informed consent.

20) Use of biologic response modifiers, such as G-CSF, within 3 week of study entry as defined by signing of informed consent.

21) Pregnant or breast-feeding subjects

22) Substance abuse medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results

23) Known or suspected allergy to sorafenib

24) Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study

25) Subjects unable to swallow oral medications. This applies to subjects with severe obstruction of the upper GI tract that require gavage.

26) Investigational drug therapy outside of this trial during or within 4 weeks of study entry, as defined by the signing of informed consent.

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Links
Registration Number: NCT00692770
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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