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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
PD Dr. med. Matthias Dollinger, Martin-Luther-Universität Halle-Wittenberg
ClinicalTrials.gov Identifier:
NCT01272557
First received: January 6, 2011
Last updated: March 31, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Liver Carcinoma
Drug: Doxorubicin
Drug: Sorafenib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Sorafenib Plus Doxorubicin Versus Sorafenib Alone for the Treatment of Advanced Hepatocellular Carcinoma: a Randomized Phase II Trial

Resource links provided by NLM:


Further study details as provided by Martin-Luther-Universität Halle-Wittenberg:

Primary Outcome Measures:
  • Time to progression (TTP) according to RECIST 1.1 criteria [ Time Frame: 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • • 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 [ Time Frame: 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). ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 170
Study Start Date: December 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Sorafenib 400 mg bid (oral) continuously
Sorafenib 400 mg bid (oral) continuously until progression or unacceptable toxicity).
Drug: Sorafenib
Sorafenib 400 mg bid (oral) continuously
Experimental: q22d: Doxorubicin 60 mg/m2 i.v d1, Sorafenib 400 mg bid d3-19
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
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).

  Eligibility

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

Inclusion Criteria:

  • 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
  • Total bilirubin ≤ 3 mg/dl
  • ALT and AST ≤ 5 x upper limit of normal
  • Alkaline phosphatase < 4 x upper limit of normal
  • PT-INR/PTT < 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as warfarin, phenprocoumon or heparin will NOT be allowed to participate]
  • Serum creatinine ≤ 1.5 x upper limit of normal
  • Signed and dated informed consent before start of any study specific procedure

Exclusion Criteria:

  • 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
  • Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Women enrolled in this trial must use adequate barrier birth control measures during the course of the trial for at least 6 months after last administration of doxorubicin and 2 months after the last administration of sorafenib.
  • Severe concomitant disease or psychiatric disorders
  • Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
  • Known severe hypersensitivity to sorafenib, doxorubicin or any of the excipients
  • Patients unable to swallow oral medications
  • Incompliance / contraindications against study medication

Excluded therapies and medications, previous and concomitant:

  • Previous systemic therapy for HCC
  • Anticancer chemotherapy or immunotherapy or targeted therapy (except study medication) during the study or within 4 weeks of study entry.
  • Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy will be allowed). Major surgery within 4 weeks of start of study
  • Autologous bone marrow transplant or stem cell rescue within 4 months of study
  • Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. [G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator, however they may not be substituted for a required dose reduction.] [Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study]
  • Patients receiving anticoagulation therapy or ASS >100 mg/d
  • Investigational drug therapy outside of this trial during or within 4 weeks of study entry
  • Prior exposure to the study drug.
  • Any St. John's wort containing remedy
  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: NCT01272557

Locations
Germany
Medizinische Klinik und Poliklinik, Heinrich-Heine-Universität
Düsseldorf, Germany, 40225
Martin-Luther-University Halle-Wittenberg
Halle (Saale), Germany, D-06099
Universitätsklinikum des Saarlande
Homburg/Saar, Germany, 66421
Ortenau Klinikum Lahr-Ettenheim
Lahr, Germany, 77933
Universitätsklinikum Leipzig
Leipzig, Germany, 04013
Klinikum Ludwigsburg
Ludwigsburg, Germany, 71640
Sponsors and Collaborators
PD Dr. med. Matthias Dollinger
  More Information

No publications provided

Responsible Party: PD Dr. med. Matthias Dollinger, PD. Dr. med., Martin-Luther-Universität Halle-Wittenberg
ClinicalTrials.gov Identifier: NCT01272557     History of Changes
Other Study ID Numbers: SoraDox
Study First Received: January 6, 2011
Last Updated: March 31, 2014
Health Authority: Germany: German Institute of Medical Documentation and Information

Keywords provided by Martin-Luther-Universität Halle-Wittenberg:
HCC

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Adenocarcinoma
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Liver Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Doxorubicin
Liposomal doxorubicin
Sorafenib
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 21, 2014