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

Overview[ - collapse ][ - ]

Purpose 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).
ConditionHepatocellular Carcinoma
InterventionDrug: Sorafenib
Drug: Doxorubicin
PhasePhase 2
SponsorMemorial Sloan-Kettering Cancer Center
Responsible PartyMemorial Sloan-Kettering Cancer Center
ClinicalTrials.gov IdentifierNCT01840592
First ReceivedApril 23, 2013
Last UpdatedApril 23, 2014
Last verifiedApril 2014

Tracking Information[ + expand ][ + ]

First Received DateApril 23, 2013
Last Updated DateApril 23, 2014
Start DateApril 2013
Estimated Primary Completion DateApril 2015
Current Primary Outcome Measuresoverall survival [Time Frame: 6 months] [Designated as safety issue: No]
Current Secondary Outcome Measures
  • median time to progression [Time Frame: 2 years] [Designated as safety issue: No]
  • median progression free survival [Time Frame: 2 years] [Designated as safety issue: No]
  • median overall survival [Time Frame: 2 years] [Designated as safety issue: No]
  • toxicity [Time Frame: 2 years] [Designated as safety issue: Yes]Toxicity rate will be reported by type and severity according to the NCI common toxicity criteria version 4 and descriptive statistics will be provided.

Descriptive Information[ + expand ][ + ]

Brief TitleSorafenib Plus Doxorubicin in Patients With Advanced Hepatocellular Carcinoma With Disease Progression on Sorafenib
Official TitlePhase II Study of Sorafenib Plus Doxorubicin in Patients With Advanced Hepatocellular Carcinoma With Disease Progression on Sorafenib
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).
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 2
Study DesignEndpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionHepatocellular Carcinoma
InterventionDrug: Sorafenib
Drug: Doxorubicin
Study Arm (s)Experimental: Sorafenib plus Doxorubicin
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.

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment30
Estimated Completion DateApril 2015
Estimated Primary Completion DateApril 2015
Eligibility Criteria
Inclusion Criteria:

- 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.

- Patients with a history of hypertension should be well controlled (< 140/90 mmHg) on
a regimen of anti-hypertensive therapy.

- Brain metastases are allowed if well controlled and without seizures.

- Prior palliative radiation therapy to bone sites is allowed as long as it is
completed more than two weeks ago.

Exclusion Criteria:

- 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.
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: Ghassan Abou-Alfa, MD
646-888-4184
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT01840592
Other Study ID Numbers12-259
Has Data Monitoring CommitteeNot Provided
Information Provided ByMemorial Sloan-Kettering Cancer Center
Study SponsorMemorial Sloan-Kettering Cancer Center
CollaboratorsBayer
Investigators Principal Investigator: Ghassan Abou-Alfa, MD Memorial Sloan-Kettering Cancer Center
Verification DateApril 2014

Locations[ + expand ][ + ]

Memorial Sloan-Kettering Cancer Center at Basking Ridge
Basking Ridge, New Jersey, United States
Contact: Ghassan Abou-Alfa, MD | 646-888-4184
Recruiting
Memorial Sloan-Kettering Cancer Center @ Suffolk
Commack, New York, United States, 11725
Contact: Ghassan Abou-Alfa, MD | 646-888-4184
Recruiting
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Contact: Ghassan Abou-Alfa, MD | 646-888-4184
Principal Investigator: Ghassan Abou-Alfa, MD
Recruiting
Memorial Sloan-Kettering Cancer Center at Mercy Medical Center
Rockville Centre, New York, United States, 11570
Contact: Ghassan Abou-Alfa, MD | 646-888-4184
Recruiting
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center
Sleepy Hollow, New York, United States, 10591
Contact: Ghassan Abou-Alfa, MD | 646-888-4184
Recruiting