Sorafenib Plus Doxorubicin in Patients With Advanced Hepatocellular Carcinoma With Disease Progression on Sorafenib
Primary Purpose
Hepatocellular Carcinoma
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sorafenib
Doxorubicin
Sponsored by
About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Liver, Sorafenib, Doxorubicin, 12-259
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.
Sites / Locations
- Memorial Sloan Kettering Cancer Center at Basking Ridge
- Memorial Sloan Kettering Cancer Center @ Suffolk
- Memorial Sloan Kettering West Harrison
- Memorial Sloan Kettering Cancer Center
- Memorial Sloan Kettering Cancer Center at Mercy Medical Center
- Memorial Sloan Kettering Cancer Center at Phelps Memorial Hospital Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Sorafenib plus Doxorubicin
Arm Description
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.
Outcomes
Primary Outcome Measures
overall survival
Secondary Outcome Measures
median time to progression
median progression free survival
median overall survival
toxicity
Toxicity rate will be reported by type and severity according to the NCI common toxicity criteria version 4 and descriptive statistics will be provided.
Full Information
NCT ID
NCT01840592
First Posted
April 23, 2013
Last Updated
May 1, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Bayer, National Comprehensive Cancer Network
1. Study Identification
Unique Protocol Identification Number
NCT01840592
Brief Title
Sorafenib Plus Doxorubicin in Patients With Advanced Hepatocellular Carcinoma With Disease Progression on Sorafenib
Official Title
Phase II Study of Sorafenib Plus Doxorubicin in Patients With Advanced Hepatocellular Carcinoma With Disease Progression on Sorafenib
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 2013 (Actual)
Primary Completion Date
April 2024 (Anticipated)
Study Completion Date
April 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Bayer, National Comprehensive Cancer Network
4. Oversight
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
Liver, Sorafenib, Doxorubicin, 12-259
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sorafenib plus Doxorubicin
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Sorafenib
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Primary Outcome Measure Information:
Title
overall survival
Time Frame
6 months
Secondary Outcome Measure Information:
Title
median time to progression
Time Frame
2 years
Title
median progression free survival
Time Frame
2 years
Title
median overall survival
Time Frame
2 years
Title
toxicity
Description
Toxicity rate will be reported by type and severity according to the NCI common toxicity criteria version 4 and descriptive statistics will be provided.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ghassan Abou-Alfa, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center at Basking Ridge
City
Basking Ridge
State/Province
New Jersey
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center @ Suffolk
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
Memorial Sloan Kettering West Harrison
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center at Mercy Medical Center
City
Rockville Centre
State/Province
New York
ZIP/Postal Code
11570
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center at Phelps Memorial Hospital Center
City
Sleepy Hollow
State/Province
New York
ZIP/Postal Code
10591
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
32841541
Citation
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.
Results Reference
derived
Links:
URL
http://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center
Learn more about this trial
Sorafenib Plus Doxorubicin in Patients With Advanced Hepatocellular Carcinoma With Disease Progression on Sorafenib
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