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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborators:
Bayer
National Comprehensive Cancer Network
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01840592
First received: April 23, 2013
Last updated: May 6, 2014
Last verified: May 2014
  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).


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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Sorafenib Plus Doxorubicin in Patients With Advanced Hepatocellular Carcinoma With Disease Progression on Sorafenib

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • overall survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]

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.


Estimated Enrollment: 30
Study Start Date: April 2013
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Sorafenib Drug: Doxorubicin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01840592

Contacts
Contact: Ghassan Abou-Alfa, MD 646-888-4184
Contact: Leonard Saltz, MD 646-888-4181

Locations
United States, New Jersey
Memorial Sloan-Kettering Cancer Center at Basking Ridge Recruiting
Basking Ridge, New Jersey, United States
Contact: Ghassan Abou-Alfa, MD    646-888-4184      
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Ghassan Abou-Alfa, MD    646-888-4184      
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Ghassan Abou-Alfa, MD    646-888-4184      
Contact: Leonard Saltz, MD    646-888-4181      
Principal Investigator: Ghassan Abou-Alfa, MD         
Memorial Sloan-Kettering Cancer Center at Mercy Medical Center Recruiting
Rockville Centre, New York, United States, 11570
Contact: Ghassan Abou-Alfa, MD    646-888-4184      
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Ghassan Abou-Alfa, MD    646-888-4184      
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Bayer
National Comprehensive Cancer Network
Investigators
Principal Investigator: Ghassan Abou-Alfa, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01840592     History of Changes
Other Study ID Numbers: 12-259
Study First Received: April 23, 2013
Last Updated: May 6, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Liver
Sorafenib
Doxorubicin
12-259

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

ClinicalTrials.gov processed this record on September 14, 2014