A Randomized 2-Arm, Open Label, Phase II Study of BMS-582664, Administered Orally At A Dose of 800 mg Daily or Doxorubicin Administered Intravenously At A Dose of 60 mg/m2 Every 3 Weeks In Patients with Unresectable, Locally Advanced or Metastatic Hepatocellular CarcinomaRevised Protocol Number 01, incorporating Amendment 02+ Pharmacogenetics Blood Sample Amendment Number 01 - Site Specific, version 1.0 dated 29-Apr-06

• Conditions: nresectable, advanced or metastatic hepatocellular carcinoma; MedDRA version: 8.1Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectable

• Registration Number: EUCTR2006-001012-68-GB
• Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-11-23
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 130

Inclusion Criteria

1) Signed written informed consent

Target population
2) Patient with diagnosis of hepatocellular carcinoma meeting the criteria below:
a) Biopsy-proven HCC (Histology or cytology)
OR
b) Radiological evidence of HCC by contrast-enhanced CT scan or contrastenhanced MRI
AND
i) Serology positive for Hepatitis B or C
AND
ii) Alpha fetoprotein > 400 µg/L
3) Not appropriate for curative surgical resection.
4) Subjects who have received local therapy such as surgery, chemoembolization, radiation therapy, hepatic arterial embolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation are eligible, provided that they either have a index lesion which has not been subjected to local therapy and/or the index lesion(s) within the field of the local therapy has shown an increase of = 25% in size. Local therapy must be completed at least 4 weeks prior to the baseline scan.
5) Measurable disease
All patients must have at least one previously un-irradiated, bi-dimensionally measurable lesion by CT or magnetic resonance imaging (MRI) scan of = 20 mm. Triphasic spiral CT or MRI scans are preferred when such equipment is available. All CT scans should employ a hepatoma protocol” image capture technique. The following are not considered measurable lesions:
a) Lesions seen on colonoscopy examination or barium studies
b) Ascites
6) More than 4 weeks since surgery (with the exception of venous port access)
7) Cancer for the Liver Italian Program” Score (CLIP) = 3
a) No evidence of encephalopathy
8) ECOG performance status of 0, 1, 2
9) Adequate bone marrow function:
a) Absolute neutrophil count = 1500/mm3
b) Platelet count = 80,000/mm3
c) Hemoglobin = 9 g/dL
10) Adequate hepatic function:
a) Total bilirubin = 2.5 mg/dL
b) AST/ALT = 5 times the upper limit of normal (ULN)
c) Serum albumin > 2.8 g/dL
d) PT or INR = 1.8 times ULN
11) Adequate renal function:
a) Creatinine = 2.0 mg/dL, OR
b) Creatinine clearance = 45 mL/min based on Cockcroft formula
12) Screening blood pressure of < 150/100 mmHg
13) Left ventricular ejection fraction (LVEF) = 50%

Age and Sex
14) Men and women, ages 18 and older.
Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the study in such a manner that the risk of pregnancy is minimized.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Sex and Reproductive Status
1) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 12 weeks after the study.
2) WOCBP not using an acceptable method of contraception sufficient to prevent pregnancy according to the instructions of the Principal Investigator.
3) Women who are pregnant or breastfeeding
4) Women with a positive blood serum pregnancy test on enrollment or prior to study drug administration.

Target Disease Exceptions
5) Exclude patients with CLIP score >3.

Medical History and Concurrent Diseases
6) Active bacterial infections, HIV/AIDS or other severe disease that would preclude study participation.
7) Gastrointestinal tract disease or prior surgery, resulting in an inability to take or absorb oral medication.
8) Other primary malignancy except carcinoma in situ of the cervix or urinary bladder or non-melanoma skin cancer.
9) Mental incapacitation or psychiatric illness that would preclude study participation
10) Uncontrolled or significant cardiovascular disease including: myocardial infarction within 12 months, uncontrolled angina within 6 months, Class III-IV New York Heart Association (NYHA) congestive heart failure, grade 3 cardiac valve dysfunction

Physical and Laboratory Test Findings
11) Clinically significant ascites refractory to diuretic therapy
12) Presence of portal-systemic encephalopathy
13) Evidence of portal hypertension with bleeding esophageal or gastric varices within the past 2 months
a) Prior variceal bleed permitted if patient has undergone banding and there has been no evidence of bleeding for 2 months
14) Hyponatremia with sodium < 125 mEq/L

Allergies and Adverse Drug Reactions
15) History of allergy to BMS-582664 or related compounds.

Prohibited Therapies and/or Medications
16) Prior systemic therapy for HCC, including systemic chemotherapy, biological therapy, or hormone therapy.
17) Patients with previous thalidomide or anti-angiogenesis therapy

Other Exclusion Criteria
18) Prisoners or patients who are compulsorily detained
19) Subjects with a history of bleeding disorders and thrombosis, including portal vein thrombosis coagulopathy, and are on chronic anti-platelet therapy (aspirin > 300 mg/day, clopidrogel; patients entering trial on warfarin should have frequent monitoring of INR for at least the first month on study and may require longer monitoring to insure that degree of anticoagulation does not go outside the therapeutic range.)
20) Subjects with fibrolamellar disease
21) Subjects with portal-caval shunts
22) Subjects who are on a liver transplant list
23) Subjects who have any known history of known brain metastases. Should patient have any signs and symptoms of possible brain metastases, a CT/MRI of the brain should be conducted prior to enrollment as clinically indicated.
24) Subjects with hepatitis B DNA levels = 1,650 IU/ml using the Roche Taqman assay.
25) Subjects with centrally located cavitating lung lesions.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified