Trial of TRC105 and Sorafenib in Patients With HCC
Primary Purpose
Hepatocellular Carcinoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Carotuximab (TRC105)
Sorafenib
Sponsored by

About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring TRC105, CD105, Endoglin, Angiogenesis inhibitor, HCC, TKI, Tyrosine Kinase Inhibitor, Sorafenib, Nexavar
Eligibility Criteria
Inclusion Criteria:
- Patients must have confirmed hepatocellular carcinoma (HCC) by histopathology or imaging criteria according to AASLD guidelines.
- Patients must have disease that is not amenable to potentially curative resection or ablative techniques or that has recurred following ablative techniques. In addition, disease must not be amenable to transhepatic arterial chemoembolization (TACE) or must have progressed on TACE. Patients must not be candidates for liver transplantation.
- If liver cirrhosis is present, patient must have a Child-Pugh A or B (7 points) classification.
- No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission per investigators' clinical judgment.
- Measurable disease by RECIST 1.1 (Phase 2 only)
- Age of 18 years or older
- ECOG performance status ≤ 1
- Resolution of all acute adverse events resulting from prior cancer therapies to NCI CTCAE grade ≤ 1 or baseline
- Adequate organ function
- Willingness and ability to consent to participate in study
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
- Men who are sterile OR agree to use at least two forms of a reliable and highly effective method of birth control and to not donate sperm and for at least 180 days following last dose of TRC105 or sorafenib.
- Woman of non-child bearing potential due to surgical sterilization confirmed by medical history or menopause, OR woman of child bearing potential who test negative for pregnancy at time of enrollment based on serum pregnancy test and agree to use at least 2 forms of a reliable and highly effective method of birth control during the study and for at least 180 days after stopping TRC105 or sorafenib.
Exclusion Criteria:
- Prior anticancer systemic therapy
- Current treatment on another therapeutic clinical trial
- Prior radiation therapy within 28 days of starting the study treatment
- No major surgical procedure or significant traumatic injury within 6 weeks prior to study registration, and must have fully recovered from any such procedure.
- Proteinuria
- Uncontrolled chronic hypertension defined as systolic > 150 or diastolic > 90 despite optimal therapy.
- History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
- Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, PTCA or CABG within the past 6 months.
- Active bleeding or pathologic condition that carries a high risk of bleeding. No bleeding diathesis.
- Thrombolytic use within 10 days prior to first day of study therapy
- History of hemorrhage or hemoptysis (> ½ teaspoon bright red blood) within 3 months of starting study treatment
- Need for anticoagulation
- History of liver transplant
- History of bleeding esophageal varices in previous 6 months, which have not been adequately managed with banding or sclerotherapy.
- History of peptic ulcer disease within 3 months of treatment.
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
- Patients may not have received a strong CYP3A4 inducer within 12 days prior to registration
- Patients with known hypersensitivity to Chinese hamster ovary products or other recombinant human, chimeric, or humanized antibodies.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality
- Ascites or pleural effusion requiring intervention or that required intervention within the last month and has recurred
- Pericardial effusion (except trace effusion identified by echocardiogram)
Sites / Locations
- University of Alabama
- University Hospitals
- MD Anderson
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Carotuximab (TRC105) and Sorafenib
Arm Description
Carotuximab (TRC105) in combination with standard dose Sorafenib.
Outcomes
Primary Outcome Measures
Number of Patients Who Experience Dose Limiting Toxicities by Dose Level
If 1 of 3 patients experienced a DLT, the dose level was expanded to 6 patients. The maximum tolerated dose (MTD) would have been exceeded if ≥ 33% of patients experience DLT at a given dose level. DLT occurred when a patient had 1 or more toxicities outlined in the protocol that was considered at least possibly related to TRC105 during the first 4 months of participation in the trial. The number of DLTs by dose cohort have been presented.
Overall Response Rate (ORR)
Number of patients with a response (PR or CR) are included by dose level. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Patients must have had a screening scan and at least 1 on study scan to be eligible for RECIST 1.1 evaluation.
Secondary Outcome Measures
Pharmacokinetic Profile of TRC105 When Given With Sorafenib
Steady state mean trough serum concentrations by dose level of TRC105 after 5 weeks of dosing were measured using validated methods after 5 weeks of dosing.
TRC105 Immunogenicity as Assessed by Anti-Product Antibody (APA)
Number of patients who tested positive for antibodies to TRC105 by dose level. Anti-Product Antibody (APA) concentrations were measured using validated ELISA methods.
Full Information
NCT ID
NCT02560779
First Posted
September 10, 2015
Last Updated
July 2, 2020
Sponsor
Tracon Pharmaceuticals Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02560779
Brief Title
Trial of TRC105 and Sorafenib in Patients With HCC
Official Title
An Open Label Phase 1B/2 Trial of TRC105 and Sorafenib in Patients With Hepatocellular Carcinoma (HCC)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
November 2016 (Actual)
Primary Completion Date
August 2019 (Actual)
Study Completion Date
August 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tracon Pharmaceuticals Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of the phase 1b portion is to evaluate safety and tolerability and determine a recommended phase 2 dose for TRC105 when added to standard dose sorafenib in patients with hepatocellular carcinoma. Up to 18 patients will be treated.
The purpose of the phase 2 portion is to estimate the ORR of patients with hepatocellular carcinoma by RECIST 1.1. Up to 21 patients will be treated in phase 2.
Detailed Description
Sorafenib is an oral multikinase inhibitor targeting several receptor tyrosine kinases, including the VEGF receptor (VEGFR), implicated in pathologic angiogenesis, tumor growth, and cancer progression. Sorafenib is approved for the treatment of unresectable hepatocellular carcinoma (HCC). TRC105 is an antibody to endoglin, an important angiogenic target on proliferating endothelial cells that is distinct from VEGFR. TRC105 inhibits angiogenesis, tumor growth and metastases and complements the activity of bevacizumab and multi-kinase inhibitors that target the VEGFR in preclinical models. Together, the use of TRC105 with sorafenib may result in more effective angiogenesis inhibition and improved clinical efficacy over that seen with sorafenib alone.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
TRC105, CD105, Endoglin, Angiogenesis inhibitor, HCC, TKI, Tyrosine Kinase Inhibitor, Sorafenib, Nexavar
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Carotuximab (TRC105) and Sorafenib
Arm Type
Experimental
Arm Description
Carotuximab (TRC105) in combination with standard dose Sorafenib.
Intervention Type
Drug
Intervention Name(s)
Carotuximab (TRC105)
Other Intervention Name(s)
Chimeric Antibody (TRC105) to CD105
Intervention Description
Bi-weekly iv TRC105 (15 mg/kg) will be given with 400mg sorafenib twice daily in the phase 1B portion of the study. Weekly iv TRC105 (10 mg/kg) will be given with 400mg sorafenib twice daily in the phase 2 portion of the study.
Intervention Type
Drug
Intervention Name(s)
Sorafenib
Other Intervention Name(s)
Nexavar
Intervention Description
400 mg of sorafenib will be given twice daily.
Primary Outcome Measure Information:
Title
Number of Patients Who Experience Dose Limiting Toxicities by Dose Level
Description
If 1 of 3 patients experienced a DLT, the dose level was expanded to 6 patients. The maximum tolerated dose (MTD) would have been exceeded if ≥ 33% of patients experience DLT at a given dose level. DLT occurred when a patient had 1 or more toxicities outlined in the protocol that was considered at least possibly related to TRC105 during the first 4 months of participation in the trial. The number of DLTs by dose cohort have been presented.
Time Frame
4 months
Title
Overall Response Rate (ORR)
Description
Number of patients with a response (PR or CR) are included by dose level. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Patients must have had a screening scan and at least 1 on study scan to be eligible for RECIST 1.1 evaluation.
Time Frame
4 months
Secondary Outcome Measure Information:
Title
Pharmacokinetic Profile of TRC105 When Given With Sorafenib
Description
Steady state mean trough serum concentrations by dose level of TRC105 after 5 weeks of dosing were measured using validated methods after 5 weeks of dosing.
Time Frame
5 weeks
Title
TRC105 Immunogenicity as Assessed by Anti-Product Antibody (APA)
Description
Number of patients who tested positive for antibodies to TRC105 by dose level. Anti-Product Antibody (APA) concentrations were measured using validated ELISA methods.
Time Frame
19 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must have confirmed hepatocellular carcinoma (HCC) by histopathology or imaging criteria according to AASLD guidelines.
Patients must have disease that is not amenable to potentially curative resection or ablative techniques or that has recurred following ablative techniques. In addition, disease must not be amenable to transhepatic arterial chemoembolization (TACE) or must have progressed on TACE. Patients must not be candidates for liver transplantation.
If liver cirrhosis is present, patient must have a Child-Pugh A or B (7 points) classification.
No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission per investigators' clinical judgment.
Measurable disease by RECIST 1.1 (Phase 2 only)
Age of 18 years or older
ECOG performance status ≤ 1
Resolution of all acute adverse events resulting from prior cancer therapies to NCI CTCAE grade ≤ 1 or baseline
Adequate organ function
Willingness and ability to consent to participate in study
Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
Men who are sterile OR agree to use at least two forms of a reliable and highly effective method of birth control and to not donate sperm and for at least 180 days following last dose of TRC105 or sorafenib.
Woman of non-child bearing potential due to surgical sterilization confirmed by medical history or menopause, OR woman of child bearing potential who test negative for pregnancy at time of enrollment based on serum pregnancy test and agree to use at least 2 forms of a reliable and highly effective method of birth control during the study and for at least 180 days after stopping TRC105 or sorafenib.
Exclusion Criteria:
Prior anticancer systemic therapy
Current treatment on another therapeutic clinical trial
Prior radiation therapy within 28 days of starting the study treatment
No major surgical procedure or significant traumatic injury within 6 weeks prior to study registration, and must have fully recovered from any such procedure.
Proteinuria
Uncontrolled chronic hypertension defined as systolic > 150 or diastolic > 90 despite optimal therapy.
History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, PTCA or CABG within the past 6 months.
Active bleeding or pathologic condition that carries a high risk of bleeding. No bleeding diathesis.
Thrombolytic use within 10 days prior to first day of study therapy
History of hemorrhage or hemoptysis (> ½ teaspoon bright red blood) within 3 months of starting study treatment
Need for anticoagulation
History of liver transplant
History of bleeding esophageal varices in previous 6 months, which have not been adequately managed with banding or sclerotherapy.
History of peptic ulcer disease within 3 months of treatment.
Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
Patients may not have received a strong CYP3A4 inducer within 12 days prior to registration
Patients with known hypersensitivity to Chinese hamster ovary products or other recombinant human, chimeric, or humanized antibodies.
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality
Ascites or pleural effusion requiring intervention or that required intervention within the last month and has recurred
Pericardial effusion (except trace effusion identified by echocardiogram)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charles Theuer, MD, PhD
Organizational Affiliation
Tracon Pharmaceuticals Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-3300
Country
United States
Facility Name
University Hospitals
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
MD Anderson
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Trial of TRC105 and Sorafenib in Patients With HCC
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