Sorafenib Plus Doxorubicin Versus Sorafenib Alone for the Treatment of Advanced Hepatocellular Carcinoma: a Randomized Phase II Trial

NCT01272557 | Unknown Phase 2 DMC

• 1 other identifier: SoraDox
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 6

Brief Summary

This study is a prospective, randomized, open-label, multicenter phase IIB trial in order to determine time to progression of the combination therapy sorafenib plus doxorubicin against standard-of-care sorafenib in advanced HCC not amenable to non-systemic treatment.

Conditions

Liver Carcinoma

Keywords

HCC

Outcome Measures

Primary Outcomes (1)

• Time to progression (TTP) according to RECIST 1.1 criteria

  The follow-up period ends 12 months after enrolment of the last patient (end of study visit of the last patient unless he died earlier

Secondary Outcomes (1)

• • Assessment of overall survival (OS) of disease control rate (CR, PR, SD) to RECIST 1.1 criteria and to EASL criteria • Assessment of safety and quality of life (FACT-Hep) and potential of biomarkers to predict the tumor response

  The follow-up period ends 12 months after enrolment of the last patient (end of study visit of the last patient unless he died earlier).

Study Arms (2)

Sorafenib 400 mg bid (oral) continuously

ACTIVE COMPARATOR

Sorafenib 400 mg bid (oral) continuously until progression or unacceptable toxicity).

Drug: Sorafenib

q22d: Doxorubicin 60 mg/m2 i.v d1, Sorafenib 400 mg bid d3-19

EXPERIMENTAL

During trial therapy period in Arm-A treated patients will receive doxorubicin infusion with 60mg/m² on day 1 every 21 days for maximum of 18 weeks (or 6 cycles) until a maximal dose of 360mg/m² are reached. Sorafenib 400mg bid (oral) will be administered from day 3-19 every 21 days during the trial therapy period

Drug: Doxorubicin

Interventions

Doxorubicin DRUG

Doxorubicin 60 mg/m2 i.v. on day 1 every 21 days Sorafenib 400 mg bid (oral) from day 3-19 every 21 days. Maximum accumulative dose of doxorubicin: 360 mg/m2 (thereafter sorafenib monotherapy continuously until progression or unacceptable toxicity).

q22d: Doxorubicin 60 mg/m2 i.v d1, Sorafenib 400 mg bid d3-19

Sorafenib DRUG

Sorafenib 400 mg bid (oral) continuously

Sorafenib 400 mg bid (oral) continuously

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Non-resectable locally advanced or metastasized HCC
• Subjects must have at least one tumor lesion that meets both of the following criteria:
• the lesion can be accurately measured in at least one dimension according to RECIST 1.1
• the lesion has not been previously treated with local therapy (such as surgery, radiation therapy, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation)
• Subjects who have received local therapy (such as surgery, radiation therapy, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation) are eligible, provided that they have a target lesion which has not been subjected to local therapy. Local therapy must be completed at least 4 weeks prior to the baseline scan.
• Confirmation of disease by histology
• Liver function: Child Pugh stage A/B (5-7 points) only
• Tumor stage: BCLC stage C (or better)
• ECOG performance status 0-2
• Life expectancy of at least 12 weeks
• Age ≥ 18 years
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening and within 4 weeks before start of treatment:
• Hemoglobin ≥ 9.0 g/dl
• Absolute neutrophil count (ANC) ≥1.500/mm3
• Platelet count ≥ 70.000/μl

You may not qualify if:

• Patients eligible for resection or transplantation
• Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study. However cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis and T1) or any cancer curatively treated \> 3 years prior to entry is permitted
• Serious myocardial dysfunction: defined as absolute left ventricular ejection fraction (LVEF) \< 50%, instable coronaropathy (MI more than 6 mo prior to study entry is allowed), cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
• Inadequately controlled hepatic complications (varices, encephalopathy)
• Untreated active Hepatitis B including HBs-Ag carriers; patients should be started on (prophylactic) anti-viral medication even without current viral replication
• Concomitant therapy with interferon (e.g. Hepatitis B/C) during study phase
• Uncontrolled arterial hypertension with systolic blood pressure \>160 mmHg or diastolic blood pressure \> 90 mm Hg despite optimal treatment
• Known history of HIV infection
• Active clinically serious infections (\> grade 2 NCI-CTC version 3.0)
• Symptomatic metastatic brain or meningeal tumors (unless the patient is \> 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry)
• Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
• History of organ allograft
• Patients with evidence or history of bleeding diathesis
• Thrombotic or embolic events within the last 6 months
• Serious non-healing wound, fracture, or ulcer

Sponsors & Collaborators

• PD Dr. med. Matthias Dollinger: lead

Study Sites (6)

Medizinische Klinik und Poliklinik, Heinrich-Heine-Universität

Düsseldorf, 40225, Germany

Location

Martin-Luther-University Halle-Wittenberg

Halle, D-06099, Germany

Location

Universitätsklinikum des Saarlande

Homburg/Saar, 66421, Germany

Location

Ortenau Klinikum Lahr-Ettenheim

Lahr, 77933, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04013, Germany

Location

Klinikum Ludwigsburg

Ludwigsburg, 71640, Germany

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Doxorubicin; Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PD. Dr. med.

Study Record Dates

• First Submitted: January 6, 2011
• First Posted: January 7, 2011
• Study Start: December 1, 2010
• Primary Completion: September 1, 2014
• Study Completion: December 1, 2014
• Last Updated: April 1, 2014

Record last verified: 2014-03

Locations

DE (6)