Phase II randomized study of nemorubicin hydrochloride (PNU-152243A) or doxorubicin administered in adult patients with unresectable hepatocellular carcinoma

• Conditions: Hepatocellular Carcinoma; MedDRA version: 8.1Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectable

• Registration Number: EUCTR2006-000798-31-DE
• Lead Sponsor: erviano Medical Sciences S.r.l.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-10-11
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 95

Inclusion Criteria

1 - Presence of unresectable HCC, not amenable to radiofrequency ablation (or other ablative techniques), microscopically confirmed HCC, either newly diagnosed or relapsing after prior surgery or other prior ablative techniques (e.g., embolization, radiofrequency, percuteneous ethanol injection [PEI], provided that the lesion(s) present at study entry are vascularized through hepatic artery). If biopsy is contraindicated, the following will be accepted as evidence of HCC:
a computerized tomography (CT) or magnetic resonance imaging (MRI) and an AFP level of >/= 400 ng/mL or two separate imaging assessments, independently of AFP value.
2 - Tumor staging at study entry CLIP 0 or 1 or 2, no Child-Pugh stage C and no portal vein thrombosis
3 - At least one bidimensionally measurable lesion that is >/= 2 cm in at least 1 diameter with conventional CT scan or MRI or >/= 1 cm in at least 1 diameter with spiral CT scan
4 - Resolution of all acute toxic effects of any prior surgical procedure or other ablative techniques to NCI CTC Grade 5 - Age >/= 18 yrs of age and 6 - ECOG performance status of 0 or 1
7 - Life expectancy of at least 12 weeks
8 - Laboratory data for study entry as specified
9 - Signed and dated informed consent document indicating that the patient (or legally acceptable representative or witness in case of oral consent) has been informed of all pertinent aspects of the trial and he/she is able to comply with the treatment plan, scheduled clinic visits, laboratory tests, oncologic tests, and other study procedures.

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

1 - Histologic classification of HCC, fibrolamellar variant
2 - Child-Pugh stage C
3 - Current enrollment in another clinical trial
4 - Administration of any prior systemic treatment or intra-arterial anticancer therapy for HCC (eg, chemoembolization, chemotherapy, antibody therapy, immunotherapy, hormonal therapy, gene therapy, vaccine therapy, cytokine therapy, or experimental agents)
5 - Prior liver transplantation
6 - Administration of any prior radiotherapy to treat the tumor lesion(s) present at study entry
7 - Extrahepatic metastatic disease including known brain or leptomeningeal disease (baseline CT or MRI scan of the brain required only in case of clinical suspicion of central nervous system metastases)
8 - Patients with vascular invasion
9 - Complete obstruction of the portal vein as documented by angiography or CT or MRI scans
10 - Presence of clinically detectable ascites or pleural effusions
11 - Symptomatic ulceration of the gastric or duodenal mucosa 12 - Any known bleeding diathesis
13 - Vascular anatomical abnormalities interfering with the perfusion of the whole liver or leading to perfusion of other organs than liver
14 - Currently active second malignancy, other than non-melanoma skin cancers and /or cone-biopsied in situ carcinoma of the cervix uteri. Patients with other malignancies must have been disease free for >/= 2 years
15 - Any prior history of symptomatic congestive heart failure
16 - Any of the following in the past within the last year: myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other significant thromboembolic event
17 - Irreversible cardiac arrhythmias requiring permanent medication or uncontrolled arterial hypertension (arterial pressure >/= 200/110 mmHg)
18 - Active infection other than chronic active hepatitis. Patients with known human immunodeficiency virus (HIV) positivity or acquired-immunodeficiency-syndrome (AIDS)-related illness are not eligible
19 - Pregnancy or breast-feeding. Female patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the treatment period and in the following 90 days after the end of the treatment. Male patients must be surgically sterile or must agree to use effective contraception during the treatment period and in the following 180 days after the end of the treatment. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate
20 - Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: Evaluation of the survival rate at 7 months;Primary end point(s): Survival at 7 months: the survival time is defined as the time from the date of enrolment to the date of death. Patients known to be alive at >/= 7 months will be considered as successes in the primary efficacy analysis.;Secondary Objective: Evaluation of the antitumor efficacy in terms of response rate (RR, i.e. the proportion of patients with confirmed objective tumor response [CR or PR], or tumor downstaging, relative to the number of patients evaluable for efficacy assessment) and frequency of stable disease lasting >/= 3 months.<br>Evaluation of tumor response characteristics (including duration of response, duration of stable disease, progression free survival [PFS], and changes in alpha-fetoprotein [AFP] tumor marker levels).<br>Evaluation of overall survival.<br>Evaluation of safety.<br>Evaluation of the CYP3A4 activity by means of quinine test<br>