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Sorafenib and TRC105 in Hepatocellular Cancer

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ClinicalTrials.gov Identifier: NCT01306058
Recruitment Status : Completed
First Posted : March 1, 2011
Results First Posted : January 23, 2018
Last Update Posted : January 23, 2018
Sponsor:
Information provided by (Responsible Party):
Tim Greten, M.D., National Institutes of Health Clinical Center (CC)

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions: Hepatoma
Liver Neoplasms
Adenoma, Liver Cell
Carcinoma, Hepatocellular
Liver Neoplasms, Experimental
Interventions: Drug: TRC 105
Drug: Sorafenib

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
27 patients were enrolled. One patient signed consent but developed rapid disease progression and did not receive any treatment.

Reporting Groups
  Description
Sorafenib & TRC105 in Hepatocellular CA

CA (cancer); 15 mg/kg TRC105 intravenous (IV) every 2 weeks and 400 mg sorafenib by mouth (PO) twice per day

TRC 105: 15 mg/kg IV every 2 weeks

Sorafenib: 400 mg twice a day (bid) continuously in a 28 days cycle


Participant Flow:   Overall Study
    Sorafenib & TRC105 in Hepatocellular CA
STARTED   27 
COMPLETED   25 
NOT COMPLETED   2 
Death                1 
Enrolled but did not get treatment                1 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sorafenib & TRC105 in Hepatocellular CA

CA (cancer); 15 mg/kg TRC105 intravenous (IV) every 2 weeks and 400 mg sorafenib by mouth (PO) twice per day

TRC 105: 15 mg/kg IV every 2 weeks

Sorafenib: 400 mg twice a day (bid) continuously in a 28 days cycle


Baseline Measures
   Sorafenib & TRC105 in Hepatocellular CA 
Overall Participants Analyzed 
[Units: Participants]
 27 
Age 
[Units: Participants]
Count of Participants
 
Participants Analyzed   27 
<=18 years      0   0.0% 
Between 18 and 65 years      25  92.6% 
>=65 years      2   7.4% 
Age 
[Units: Years]
Mean (Standard Deviation)
 
Participants Analyzed   27 
   55.3  (13) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
 
Participants Analyzed   27 
Female      7  25.9% 
Male      20  74.1% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
 
Participants Analyzed   27 
Hispanic or Latino      1   3.7% 
Not Hispanic or Latino      26  96.3% 
Unknown or Not Reported      0   0.0% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
 
Participants Analyzed   27 
American Indian or Alaska Native      1   3.7% 
Asian      2   7.4% 
Native Hawaiian or Other Pacific Islander      0   0.0% 
Black or African American      10  37.0% 
White      13  48.1% 
More than one race      0   0.0% 
Unknown or Not Reported      1   3.7% 
Region of Enrollment 
[Units: Participants]
Count of Participants
 
United States   
Participants Analyzed   27 
United States   27 
Participant Etiology of Hepatocellular Cancer (HCC) [1] [2] 
[Units: Participants]
Count of Participants
 
Hepatitis B Virus (HBV)   
Participants Analyzed   25 
Hepatitis B Virus (HBV)   3 
Hepatitis C Virus (HCV)   
Participants Analyzed   25 
Hepatitis C Virus (HCV)   15 
Cryptogenic   
Participants Analyzed   25 
Cryptogenic   6 
Hematochromatosis   
Participants Analyzed   25 
Hematochromatosis   1 
[1] Hepatitis B virus is a viral infection that affects the liver. Hepatitis C virus is a virus spread by infected blood (e.g. share needles). Crytogenic means the cause of the disease is unknown. Hematochromatosis is an iron disorder in which the body has an excess of iron in the blood.
[2] One patient was enrolled and signed consent but developed rapid disease progression and did not receive any treatment. One patient developed a fatal myocardial infarction.
Baseline Child Pugh Score [1] [2] 
[Units: Participants]
Count of Participants
 
Child Pugh Score - 5   
Participants Analyzed   25 
Child Pugh Score - 5   10 
Child Pugh Score - 6   
Participants Analyzed   25 
Child Pugh Score - 6   4 
Child Pugh Score - 7   
Participants Analyzed   25 
Child Pugh Score - 7   1 
NA   
Participants Analyzed   25 
NA   10 
[1] The Modified Child-Pugh classifies the severity of liver disease according to the degree of ascites, plasma concentrations of bilirubin and albumin, the prothrombin time and degree of encephalopathy. A total score of 5-6 is considered grade A (well-compensated disease); 7-9 grade B (significant functional compromise) and 10-15 is grade C (decompensated disease). NA = not all patients had cirrhosis. You only do a Pugh Score if cirrhosis is present.
[2] One patient was enrolled and signed consent but developed rapid disease progression and did not receive any treatment. One patient developed a fatal myocardial infarction.
Number of Participants with Extrahepatic disease [1] [2] 
[Units: Participants]
Count of Participants
 
Yes   
Participants Analyzed   25 
Yes   17 
No   
Participants Analyzed   25 
No   8 
[1] Extrahepatic is defined as disease outside of the liver.
[2] One patient was enrolled and signed consent but developed rapid disease progression and did not receive any treatment. One patient developed a fatal myocardial infarction.
Prior Therapies [1] 
[Units: Participants]
Count of Participants
 
No prior intervention   
Participants Analyzed   27 
No prior intervention   9 
≥2 locoregional procedures   
Participants Analyzed   27 
≥2 locoregional procedures   7 
Previous TACE   
Participants Analyzed   27 
Previous TACE   8 
Surgery   
Participants Analyzed   27 
Surgery   5 
Ablation   
Participants Analyzed   27 
Ablation   2 
Radioembolization   
Participants Analyzed   27 
Radioembolization   2 
Transplant   
Participants Analyzed   27 
Transplant   2 
[1] Of note, some patients received more than one prior therapeutic intervention. Transcatheter arterial chemoembolization (TACE) is performed to restrict blood flow. Ablation is a procedure to destroy cardiac tissue. Radioembolization is a combination of embolization and radiation therapy to treat liver cancer. Locoregional is a recurrence of cancer at the same original site of disease. Transplant refers to a liver transplant.
Number of Participants with Liver Cirrhosis [1] [2] 
[Units: Participants]
Count of Participants
 
Yes   
Participants Analyzed   25 
Yes   15 
No   
Participants Analyzed   25 
No   10 
[1] Cirrhosis is scar tissue on the liver.
[2] One patient was enrolled and signed consent but developed rapid disease progression and did not receive any treatment. One patient developed a fatal myocardial infarction.
Eastern Cooperative Oncology Group (ECOG) Performance Status [1] [2] 
[Units: Participants]
Count of Participants
 
Grade 0   
Participants Analyzed   25 
Grade 0   8 
Grade 1   
Participants Analyzed   25 
Grade 1   17 
[1] ECOG Grade 0 is normal activity. Fully active, able to carry on all-pre-disease performance without restriction. Grade 1 is symptoms, but ambulatory. Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature. Grade 2 is in bed <50% of the time. Ambulatory and capable of all self-care, but unable to carry out any work activities. Grade 3 is in bed >50% of the time. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. Grade 4 is 100% bedridden. Completely disabled. Grade 5 is dead.
[2] One patient was enrolled and signed consent but developed rapid disease progression and did not receive any treatment. One patient developed a fatal myocardial infarction.
Participants with Hepatocellular Cancer & Fibrolamellar [1] [2] 
[Units: Participants]
Count of Participants
 
Hepatocellular Cancer (HCC)   
Participants Analyzed   25 
Hepatocellular Cancer (HCC)   24 
Fibrolamellar   
Participants Analyzed   25 
Fibrolamellar   1 
[1] HCC is liver cancer usually found in patients with cirrhosis or liver disease. Fibolamellar is a rare form of HCC. The tumor cells are mixed with fibrous layers.
[2] One patient was enrolled and signed consent but developed rapid disease progression and did not receive any treatment. One patient developed a fatal myocardial infarction.


  Outcome Measures

1.  Primary:   Phase I: Maximum Tolerated Dose (MTD) of TRC105 When Given With Standard-dose Sorafenib for Hepatocellular Cancer (HCC)   [ Time Frame: Completed in the first 28 days of treatment (cycle 1) ]

2.  Primary:   Phase II: Time to Progression (TTP) for the Combination of TR105 With Sorafenib in Hepatocellular Cancer (HCC)   [ Time Frame: 2 years ]

3.  Secondary:   Overall Response Rate (ORR) as Determined by the Standard Response Evaluation Criteria in Solid Tumors (RECIST) Criteria   [ Time Frame: 2 years ]

4.  Secondary:   Overall Response Rate (ORR) as Determined by the European Association for the Study of the Liver (EASL)-Modified Response Evaluation Criteria in Solid Tumors (RECIST) Criteria   [ Time Frame: 2 years ]

5.  Secondary:   Patients Who Developed Antidrug Antibodies   [ Time Frame: Cycle 1 Day 1, 28 days post end of study (up to 2 years) ]

6.  Secondary:   Number of Participants With Serious and Non-serious Adverse Events by Common Terminology Criteria in Adverse Events (CTCAE)v4.0   [ Time Frame: 4 years and 10.5 months ]

7.  Secondary:   Number of Participants With Dose Limiting Toxicity (DLT)   [ Time Frame: First 28 days of treatment (cycle 1) ]

8.  Secondary:   Treatment-emergent Adverse Events   [ Time Frame: 4 years and 10.5 months ]

9.  Secondary:   Median Progression-free Survival (PFS)   [ Time Frame: up to 6 months ]

10.  Secondary:   Percentage of Participants With Progression Free Survival (PFS) at 3 and 6 Months   [ Time Frame: 3 and 6 months ]

11.  Secondary:   Median Overall Survival (OS)   [ Time Frame: up to 2 years ]

12.  Secondary:   Percentage of Participants With Overall Survival (OS) at 6 and 12 Months   [ Time Frame: 6 and 12 months ]

13.  Secondary:   Number of Participants With Stable Disease, Partial Response, and Progressive Disease on Phase I and Phase II of the Clinical Trial   [ Time Frame: Every 8 weeks, up to 180 days ]

14.  Secondary:   Area Under the Plasma Concentration   [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, and prior to start of TRC105 infusion ]

15.  Secondary:   Changes in Biomarkers Vascular Endothelial Growth Factor (VEGF) and Placenta Growth Factor (PIGF)   [ Time Frame: Cycle 1 day 1, cycle 1 day 15, cycle 2 day 1, or end of study, an average of 12 weeks ]

16.  Secondary:   Changes in Biomarker Cluster of Differentiation 105 (CD105)   [ Time Frame: Cycle 1 day 1, cycle 1 day 15, cycle 2 day 1, or end of study (eos), an average of 12 weeks ]

17.  Secondary:   Percentage Signal Change in Response on Magnetic Resonance Imaging (MRI)   [ Time Frame: Baseline and Cycle 1 Day 2 and Cycle 2 Day 1, an average of 12 weeks ]

18.  Secondary:   Immunogenicity of TRC105 as Measured by Human Anti-mouse Antibody (HAMA) Formation   [ Time Frame: Baseline and then 28 days following the end of the study treatment ]
Results not yet reported.   Anticipated Reporting Date:   11/2018  


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Dr. Tim Greten
Organization: Principal Investigator
phone: 301-451-4723
e-mail: tim.greten@nih.hhs.gov


Publications:

Responsible Party: Tim Greten, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT01306058     History of Changes
Other Study ID Numbers: 110102
11-C-0102
First Submitted: February 26, 2011
First Posted: March 1, 2011
Results First Submitted: May 23, 2017
Results First Posted: January 23, 2018
Last Update Posted: January 23, 2018