Sorafenib Plus Doxorubicin in Patients With Advanced Hepatocellular Carcinoma With Disease Progression on Sorafenib

NCT01840592 | Active Not Recruiting Phase 2

• 1 other identifier: 12-259
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to find out what effects, good and/or bad, the combination of the drug sorafenib in combination with the drug doxorubicin might have on the growth and spread of liver cancer (HCC).

Conditions

Hepatocellular Carcinoma

Keywords

Liver; Sorafenib; Doxorubicin; 12-259

Outcome Measures

Primary Outcomes (1)

• overall survival

  6 months

Secondary Outcomes (4)

• median time to progression

  2 years

• median progression free survival

  2 years

• median overall survival

  2 years

• toxicity

  2 years

Study Arms (1)

Sorafenib plus Doxorubicin

EXPERIMENTAL

Doxorubicin 60 mg/m2 IV on Day 1 of each 3 weeks cycle until unacceptable toxicity Sorafenib 400 mg PO BID or last dose patient from previous sorafenib based therapy, until unacceptable toxicity or disease progression, after which sorafenib can be continued as a single agent.

Drug: Sorafenib; Drug: Doxorubicin

Interventions

Sorafenib DRUG

Sorafenib plus Doxorubicin

Doxorubicin DRUG

Sorafenib plus Doxorubicin

Eligibility Criteria

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

You may qualify if:

• Diagnosis of HCC confirmed histologically, excluding mixed HCC histology (e.g. HCC plus cholangiocarcinoma) or fibrolamellar variant.
• Prior treatment with sorafenib as single agent or in combination, with no less than 200 mg once every other day dose of sorafenib, with radiologic evidence of progression of disease.
• Measurable disease using RECIST 1.1 criteria.
• Non-cirrhotic or no more than Child-Pugh A cirrhosis.
• Expected survival of at least 3 months.
• Age ≥ 18 years.
• KPS ≥ 70%
• Fully recovered from any prior surgery and/or radiation and none within 2 weeks of initiating treatment.
• Patients may have been treated with locoregional liver directed therapies such as embolization, chemo-embolization including drug-eluting beads doxorubicin chemoembolization (prior non drug eluting beads chemoembolization with doxorubicin is excluded), radiation, radioactive microspheres, etc., provided that they either have a target lesion that has not been subjected to local therapy and/or the target lesion(s) within the field of the local therapy has shown an increase of ≥25% in the size since last treatment. Such therapy must be completed at least 4 weeks prior to treatment initiation. Patients that have received palliative radiation therapy to the bone need not wait 4 weeks to begin protocol therapy.
• Informed consent must be obtained prior to study initiation.
• Total bilirubin ≤3.0 mg/dL and no evidence of bile obstruction.
• Absolute neutrophil count (ANC) ≥1,500/μL.
• Platelets ≥75,000/μL.
• Serum creatinine ≤ 1.5 x the upper limit of normal range, or, if serum creatinine \>1.5 x the upper limit of normal range, then the creatinine clearance must be ≥ 60 mL/min.
• Subjects with active hepatitis B or C on anti-viremic compounds may remain on such treatment, except for interferon.

You may not qualify if:

• Significant cardiac disease:
• Congestive heart failure \> Class II New York Heart Association (NYHA).
• Myocardial infarction within 6 months prior to study entry.
• Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin.
• Serious myocardial dysfunction, defined as scintigraphically (MUGA, myocardial scintigram) or echocardiogram determined absolute left ventricular ejection fraction (LVEF) below normal (\<50%).
• Participation in concurrent investigational studies.
• Prior loco-regional therapy including drug-eluting beads doxorubicin chemoembolization (prior non drug eluting beads chemoembolization with doxorubicin is excluded) is allowed.
• Prior exposure to systemic intravenously given doxorubicin.
• Pregnancy or lactation.
• Uncontrolled inter-current illness or psychiatric illness or social situations that would limit compliance with study requirements.
• Subjects with history of another primary cancer, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present in the opinion of the investigator will not affect patient outcome in the setting of current HCC diagnosis. Allografts, including but not limited to liver and bone marrow transplants.
• Bleeding esophageal or gastric varices within 30 days prior to treatment initiation.
• Concomitant treatment with Rifampin or St John's Wort. Patients should discontinue these drugs at least 4 weeks prior to starting protocol treatment.
• Subjects known to be HIV positive.
• History of bleeding diathesis.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Bayer: collaborator
• National Comprehensive Cancer Network: collaborator

Study Sites (6)

Memorial Sloan Kettering Cancer Center at Basking Ridge

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering West Harrison

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Cancer Center at Mercy Medical Center

Rockville Centre, New York, 11570, United States

Location

Memorial Sloan Kettering Cancer Center at Phelps Memorial Hospital Center

Sleepy Hollow, New York, 10591, United States

Location

Related Publications (1)

• El Dika I, Capanu M, Chou JF, Harding JJ, Ly M, Hrabovsky AD, Do RKG, Shia J, Millang B, Ma J, O'Reilly EM, Abou-Alfa GK. Phase II trial of sorafenib and doxorubicin in patients with advanced hepatocellular carcinoma after disease progression on sorafenib. Cancer Med. 2020 Oct;9(20):7453-7459. doi: 10.1002/cam4.3389. Epub 2020 Aug 25.

  PMID: 32841541 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Sorafenib; Doxorubicin

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)

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

Study Officials

• Ghassan Abou-Alfa, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2013
• First Posted: April 25, 2013
• Study Start: April 1, 2013
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

US (6)