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Trial of TRC105 and Sorafenib in Patients With HCC

Sponsor
Tracon Pharmaceuticals Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02560779
Collaborator
(none)
27
Enrollment
3
Locations
1
Arm
33
Actual Duration (Months)
9
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/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.

Study Design

Study Type:
Interventional
Actual Enrollment :
27 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open Label Phase 1B/2 Trial of TRC105 and Sorafenib in Patients With Hepatocellular Carcinoma (HCC)
Actual Study Start Date :
Nov 1, 2016
Actual Primary Completion Date :
Aug 1, 2019
Actual Study Completion Date :
Aug 1, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Carotuximab (TRC105) and Sorafenib

Carotuximab (TRC105) in combination with standard dose Sorafenib.

Drug: Carotuximab (TRC105)
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.
Other Names:
  • Chimeric Antibody (TRC105) to CD105

    • Drug: Sorafenib
    400 mg of sorafenib will be given twice daily.
    Other Names:
  • Nexavar

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Patients Who Experience Dose Limiting Toxicities by Dose Level [4 months]

      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.

    2. Overall Response Rate (ORR) [4 months]

      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

    1. Pharmacokinetic Profile of TRC105 When Given With Sorafenib [5 weeks]

      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.

    2. TRC105 Immunogenicity as Assessed by Anti-Product Antibody (APA) [19 months]

      Number of patients who tested positive for antibodies to TRC105 by dose level. Anti-Product Antibody (APA) concentrations were measured using validated ELISA methods.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Patients must have confirmed hepatocellular carcinoma (HCC) by histopathology or imaging criteria according to AASLD guidelines.

    2. 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.

    3. If liver cirrhosis is present, patient must have a Child-Pugh A or B (7 points) classification.

    4. 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.

    5. Measurable disease by RECIST 1.1 (Phase 2 only)

    6. Age of 18 years or older

    7. ECOG performance status ≤ 1

    8. Resolution of all acute adverse events resulting from prior cancer therapies to NCI CTCAE grade ≤ 1 or baseline

    9. Adequate organ function

    10. Willingness and ability to consent to participate in study

    11. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

    12. 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.

    13. 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:

    1. Prior anticancer systemic therapy

    2. Current treatment on another therapeutic clinical trial

    3. Prior radiation therapy within 28 days of starting the study treatment

    4. No major surgical procedure or significant traumatic injury within 6 weeks prior to study registration, and must have fully recovered from any such procedure.

    5. Proteinuria

    6. Uncontrolled chronic hypertension defined as systolic > 150 or diastolic > 90 despite optimal therapy.

    7. History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.

    8. Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, PTCA or CABG within the past 6 months.

    9. Active bleeding or pathologic condition that carries a high risk of bleeding. No bleeding diathesis.

    10. Thrombolytic use within 10 days prior to first day of study therapy

    11. History of hemorrhage or hemoptysis (> ½ teaspoon bright red blood) within 3 months of starting study treatment

    12. Need for anticoagulation

    13. History of liver transplant

    14. History of bleeding esophageal varices in previous 6 months, which have not been adequately managed with banding or sclerotherapy.

    15. History of peptic ulcer disease within 3 months of treatment.

    16. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness

    17. Patients may not have received a strong CYP3A4 inducer within 12 days prior to registration

    18. Patients with known hypersensitivity to Chinese hamster ovary products or other recombinant human, chimeric, or humanized antibodies.

    19. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality

    20. Ascites or pleural effusion requiring intervention or that required intervention within the last month and has recurred

    21. Pericardial effusion (except trace effusion identified by echocardiogram)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama Birmingham Alabama United States 35294-3300
    2 University Hospitals Cleveland Ohio United States 44106
    3 MD Anderson Houston Texas United States 77030-4009

    Sponsors and Collaborators

    • Tracon Pharmaceuticals Inc.

    Investigators

    • Study Director: Charles Theuer, MD, PhD, Tracon Pharmaceuticals Inc.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Tracon Pharmaceuticals Inc.
    ClinicalTrials.gov Identifier:
    NCT02560779
    Other Study ID Numbers:
    • 105HCC101
    First Posted:
    Sep 25, 2015
    Last Update Posted:
    Jul 17, 2020
    Last Verified:
    Jul 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Tracon Pharmaceuticals Inc.
    TRC105
    CD105
    Endoglin
    Angiogenesis inhibitor
    HCC
    TKI
    Tyrosine Kinase Inhibitor
    Sorafenib
    Nexavar
    Additional relevant MeSH terms:
    Carcinoma
    Carcinoma, Hepatocellular
    Sorafenib

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Carotuximab (10 mg/kg wk to 15 mg/kg Bi-wk) Plus Sorafenib Carotuximab (10 mg/kg Weekly) Plus Sorafenib
    Arm/Group Description Carotuximab (TRC105) given weekly (10 mg/kg) for 2 cycles then bi-weekly iv TRC105 (15 mg/kg) with 400mg sorafenib twice daily Carotuximab (TRC105) given weekly iv (10 mg/kg) with 400mg sorafenib twice daily
    Period Title: Overall Study
    STARTED 14 13
    COMPLETED 14 13
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Carotuximab (10 mg/kg wk to 15 mg/kg Bi-wk) Plus Sorafenib Carotuximab (10 mg/kg Weekly) Plus Sorafenib Total
    Arm/Group Description Carotuximab (TRC105) given weekly (10 mg/kg) for 2 cycles then bi-weekly iv TRC105 (15 mg/kg) with 400mg sorafenib twice daily Carotuximab (TRC105) given weekly iv (10 mg/kg) with 400mg sorafenib twice daily Total of all reporting groups
    Overall Participants 14 13 27
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    6
    42.9%
    6
    46.2%
    12
    44.4%
    >=65 years
    8
    57.1%
    7
    53.8%
    15
    55.6%
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    4
    30.8%
    4
    14.8%
    Male
    14
    100%
    9
    69.2%
    23
    85.2%
    Race/Ethnicity, Customized (Number) [Number]
    Asian
    2
    14.3%
    0
    0%
    2
    7.4%
    White
    9
    64.3%
    7
    53.8%
    16
    59.3%
    Black or African American
    2
    14.3%
    5
    38.5%
    7
    25.9%
    Unknown
    1
    7.1%
    1
    7.7%
    2
    7.4%
    Region of Enrollment (participants) [Number]
    United States
    14
    100%
    13
    100%
    27
    100%

    Outcome Measures

    1. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Patients must have received at least a portion of a dose of TRC105 or sorafenib to be evaluable for assessment of DLT.
    Arm/Group Title Carotuximab (10 mg/kg wk to 15 mg/kg Bi-wk) Plus Sorafenib Carotuximab (10 mg/kg Weekly) Plus Sorafenib
    Arm/Group Description Carotuximab (TRC105) given weekly (10 mg/kg) for 2 cycles then bi-weekly iv TRC105 (15 mg/kg) with 400mg sorafenib twice daily Carotuximab (TRC105) given weekly iv (10 mg/kg) with 400mg sorafenib twice daily
    Measure Participants 14 13
    Count of Participants [Participants]
    1
    7.1%
    0
    0%
    2. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Patients must have had a screening scan and at least 1 on study scan to be eligible for RECIST 1.1 evaluation.
    Arm/Group Title Carotuximab (10 mg/kg wk to 15 mg/kg Bi-wk) Plus Sorafenib Carotuximab (10 mg/kg Weekly) Plus Sorafenib
    Arm/Group Description Carotuximab (TRC105) given weekly (10 mg/kg) for 2 cycles then bi-weekly iv TRC105 (15 mg/kg) with 400mg sorafenib twice daily Carotuximab (TRC105) given weekly iv (10 mg/kg) with 400mg sorafenib twice daily
    Measure Participants 14 11
    Count of Participants [Participants]
    2
    14.3%
    1
    7.7%
    3. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Steady state mean trough serum concentration by dose level after 5 weeks of dosing. Patients must have received all protocol required TRC105 doses to be included in the analysis. Additional analysis were not performed as TRC105 development overall was canceled due to lack of efficacy.
    Arm/Group Title Carotuximab (10 mg/kg wk to 15 mg/kg Bi-wk) Plus Sorafenib Carotuximab (10 mg/kg Weekly) Plus Sorafenib
    Arm/Group Description Carotuximab (TRC105) given weekly (10 mg/kg) for 2 cycles then bi-weekly iv TRC105 (15 mg/kg) with 400mg sorafenib twice daily Carotuximab (TRC105) given weekly iv (10 mg/kg) with 400mg sorafenib twice daily
    Measure Participants 8 3
    Mean (Standard Deviation) [ug/ML]
    14.2
    (12.1)
    44.7
    (9)
    4. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Number of patients who tested positive for antibodies to TRC105. Patients must have tested negative for TRC105 antibodies at baseline and have had an on study test performed to be included in the analysis.
    Arm/Group Title Carotuximab (10 mg/kg wk to 15 mg/kg Bi-wk) Plus Sorafenib Carotuximab (10 mg/kg Weekly) Plus Sorafenib
    Arm/Group Description Carotuximab (TRC105) given weekly (10 mg/kg) for 2 cycles then bi-weekly iv TRC105 (15 mg/kg) with 400mg sorafenib twice daily Carotuximab (TRC105) given weekly iv (10 mg/kg) with 400mg sorafenib twice daily
    Measure Participants 13 5
    Count of Participants [Participants]
    9
    64.3%
    5
    38.5%

    Adverse Events

    Time Frame Adverse events were collected while on study and for 28 days following the last dose of TRC105 or sorafenib. The longest duration of participation of any patient on study was 24 months.
    Adverse Event Reporting Description Only patients who received at least a portion of a dose of TRC105 or sorafenib were included in the safety population. Both dose groups received 10 mg/kg TRC105 for the first month. Patients assigned to the 10 mg/kg weekly (cycle 1) then 15 mg/kg every two weeks (cycle 2+) dose group who discontinued the study prior to initiating cycle 2 dosing were counted in the 10 mg/kg weekly adverse event group.
    Arm/Group Title Carotuximab (10 mg/kg wk to 15 mg/kg Bi-wk) Plus Sorafenib Carotuximab (10 mg/kg Weekly) Plus Sorafenib
    Arm/Group Description Carotuximab (TRC105) given weekly (10 mg/kg) for 2 cycles then bi-weekly iv TRC105 (15 mg/kg) with 400mg sorafenib twice daily Carotuximab (TRC105) given weekly iv (10 mg/kg) with 400mg sorafenib twice daily
    All Cause Mortality
    Carotuximab (10 mg/kg wk to 15 mg/kg Bi-wk) Plus Sorafenib Carotuximab (10 mg/kg Weekly) Plus Sorafenib
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/14 (0%) 0/13 (0%)
    Serious Adverse Events
    Carotuximab (10 mg/kg wk to 15 mg/kg Bi-wk) Plus Sorafenib Carotuximab (10 mg/kg Weekly) Plus Sorafenib
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/14 (35.7%) 9/13 (69.2%)
    Blood and lymphatic system disorders
    Anemia 1/14 (7.1%) 1/13 (7.7%)
    Cardiac disorders
    Cardiac Failure 0/14 (0%) 1/13 (7.7%)
    Gastrointestinal disorders
    Ileus 0/14 (0%) 1/13 (7.7%)
    Nausea 1/14 (7.1%) 1/13 (7.7%)
    Oesophageal Haemorrhage 0/14 (0%) 1/13 (7.7%)
    Pancreatitis 0/14 (0%) 1/13 (7.7%)
    Rectal Haemorrhage 0/14 (0%) 1/13 (7.7%)
    Upper Gastrointestinal Haemorrhage 1/14 (7.1%) 0/13 (0%)
    Vomiting 1/14 (7.1%) 1/13 (7.7%)
    Hepatobiliary disorders
    Cholangitis 1/14 (7.1%) 0/13 (0%)
    Infections and infestations
    Wound Infection 1/14 (7.1%) 0/13 (0%)
    Injury, poisoning and procedural complications
    Infusion Related Reaction 1/14 (7.1%) 0/13 (0%)
    Investigations
    Alanine Aminotransferase Increased 0/14 (0%) 1/13 (7.7%)
    Aspartate Aminotransferase Increase 0/14 (0%) 1/13 (7.7%)
    Blood Bilirubin Increased 0/14 (0%) 1/13 (7.7%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to Central Nervous System 0/14 (0%) 1/13 (7.7%)
    Nervous system disorders
    Encephalopathy 0/14 (0%) 1/13 (7.7%)
    Haemorrhage Intracranial 1/14 (7.1%) 0/13 (0%)
    Renal and urinary disorders
    Acute kidney injury 0/14 (0%) 1/13 (7.7%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 1/14 (7.1%) 0/13 (0%)
    Epstaxis 0/14 (0%) 1/13 (7.7%)
    Pleural Effusion 0/14 (0%) 2/13 (15.4%)
    Respiratory Failure 0/14 (0%) 1/13 (7.7%)
    Vascular disorders
    Hypotension 0/14 (0%) 1/13 (7.7%)
    Other (Not Including Serious) Adverse Events
    Carotuximab (10 mg/kg wk to 15 mg/kg Bi-wk) Plus Sorafenib Carotuximab (10 mg/kg Weekly) Plus Sorafenib
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 14/14 (100%) 13/13 (100%)
    Blood and lymphatic system disorders
    Anemia 6/14 (42.9%) 6/13 (46.2%)
    Microcytic Anaemia 1/14 (7.1%) 0/13 (0%)
    Cardiac disorders
    Atrial Fibrillation 0/14 (0%) 1/13 (7.7%)
    Bradycardia 0/14 (0%) 1/13 (7.7%)
    Cardiac Failure 0/14 (0%) 1/13 (7.7%)
    Coronary Artery Disease 0/14 (0%) 1/13 (7.7%)
    Sinus Tachycardia 2/14 (14.3%) 0/13 (0%)
    Tachycardia 0/14 (0%) 1/13 (7.7%)
    Ear and labyrinth disorders
    Tinnitus 1/14 (7.1%) 1/13 (7.7%)
    Endocrine disorders
    Hypothyroidism 2/14 (14.3%) 1/13 (7.7%)
    Eye disorders
    Eye Pain 1/14 (7.1%) 0/13 (0%)
    Photopsia 1/14 (7.1%) 0/13 (0%)
    Vision Blurred 0/14 (0%) 2/13 (15.4%)
    Gastrointestinal disorders
    Abdominal Pain 1/14 (7.1%) 5/13 (38.5%)
    Abdominal Distension 0/14 (0%) 2/13 (15.4%)
    Abdominal Pain Lower 1/14 (7.1%) 1/13 (7.7%)
    Abdominal Pain Upper 4/14 (28.6%) 1/13 (7.7%)
    Ascites 0/14 (0%) 1/13 (7.7%)
    Constipation 4/14 (28.6%) 6/13 (46.2%)
    Diarrhoea 4/14 (28.6%) 9/13 (69.2%)
    Dry Mouth 2/14 (14.3%) 1/13 (7.7%)
    Dysphagia 0/14 (0%) 2/13 (15.4%)
    Faeces Discoloured 0/14 (0%) 1/13 (7.7%)
    Frequent Bowel Movements 0/14 (0%) 1/13 (7.7%)
    Gastritis 0/14 (0%) 1/13 (7.7%)
    Gastrooesophageal Reflux Disease 1/14 (7.1%) 3/13 (23.1%)
    Gingival Bleeding 2/14 (14.3%) 5/13 (38.5%)
    Glossodynia 0/14 (0%) 1/13 (7.7%)
    Haematemesis 0/14 (0%) 1/13 (7.7%)
    Haematochezia 0/14 (0%) 1/13 (7.7%)
    Haemorrhoids 1/14 (7.1%) 0/13 (0%)
    Hypoaesthesia Oral 0/14 (0%) 1/13 (7.7%)
    Lip Swelling 1/14 (7.1%) 0/13 (0%)
    Melaena 1/14 (7.1%) 1/13 (7.7%)
    Mouth Haemorrhage 1/14 (7.1%) 2/13 (15.4%)
    Nausea 4/14 (28.6%) 5/13 (38.5%)
    Odynophagia 1/14 (7.1%) 0/13 (0%)
    Periodontal Disease 2/14 (14.3%) 0/13 (0%)
    Proctalgia 0/14 (0%) 1/13 (7.7%)
    Rectal Haemorrhage 0/14 (0%) 2/13 (15.4%)
    Rectal Ulcer 0/14 (0%) 1/13 (7.7%)
    Stomatitis 2/14 (14.3%) 2/13 (15.4%)
    Upper Gastrointestinal Haemorrhage 0/14 (0%) 2/13 (15.4%)
    Vomiting 2/14 (14.3%) 2/13 (15.4%)
    General disorders
    Asthenia 1/14 (7.1%) 0/13 (0%)
    Chest Pain 1/14 (7.1%) 1/13 (7.7%)
    Chills 4/14 (28.6%) 7/13 (53.8%)
    Fatigue 7/14 (50%) 13/13 (100%)
    Gait Disturbance 2/14 (14.3%) 0/13 (0%)
    Irritability 1/14 (7.1%) 0/13 (0%)
    Malaise 0/14 (0%) 1/13 (7.7%)
    Medical Device Site Bruise 0/14 (0%) 1/13 (7.7%)
    Mucosal Inflammation 2/14 (14.3%) 0/13 (0%)
    Non-Cardiac Chest Pain 0/14 (0%) 1/13 (7.7%)
    Oedema Peripheral 2/14 (14.3%) 3/13 (23.1%)
    Pyrexia 5/14 (35.7%) 4/13 (30.8%)
    Hepatobiliary disorders
    Bile Duct Obstruction 1/14 (7.1%) 0/13 (0%)
    Cholelithiasis 0/14 (0%) 1/13 (7.7%)
    Portal Vein Thrombosis 0/14 (0%) 2/13 (15.4%)
    Immune system disorders
    Drug Hypersensitivity 1/14 (7.1%) 0/13 (0%)
    Infections and infestations
    Bacteraemia 1/14 (7.1%) 0/13 (0%)
    Bronchitis 1/14 (7.1%) 0/13 (0%)
    Cellulitis 0/14 (0%) 1/13 (7.7%)
    Device Related Infection 0/14 (0%) 1/13 (7.7%)
    Pneumonia 1/14 (7.1%) 0/13 (0%)
    Scrotal Infection 1/14 (7.1%) 0/13 (0%)
    Sinusitis 2/14 (14.3%) 0/13 (0%)
    Subcutaneous Abscess 1/14 (7.1%) 0/13 (0%)
    Tooth Abscess 0/14 (0%) 1/13 (7.7%)
    Upper Respiratory Infection 1/14 (7.1%) 1/13 (7.7%)
    Urinary Tract Infection 0/14 (0%) 1/13 (7.7%)
    Injury, poisoning and procedural complications
    Arthropod Bite 1/14 (7.1%) 0/13 (0%)
    Contusion 1/14 (7.1%) 0/13 (0%)
    Fall 2/14 (14.3%) 3/13 (23.1%)
    Infusion Related Reaction 4/14 (28.6%) 4/13 (30.8%)
    Laceration 1/14 (7.1%) 1/13 (7.7%)
    Thermal Burn 1/14 (7.1%) 0/13 (0%)
    Investigations
    Alanine Aminotransferase Increased 3/14 (21.4%) 4/13 (30.8%)
    Ammonia Increased 1/14 (7.1%) 1/13 (7.7%)
    Aspartate Aminotransferase Increased 1/14 (7.1%) 4/13 (30.8%)
    Blood Alkaline Phosphatase Increased 3/14 (21.4%) 4/13 (30.8%)
    Blood Amylase Increased 4/14 (28.6%) 3/13 (23.1%)
    Blood Bilirubin Increased 2/14 (14.3%) 4/13 (30.8%)
    Blood Creatinine Increased 0/14 (0%) 2/13 (15.4%)
    Blood Phosphorus Decreased 1/14 (7.1%) 0/13 (0%)
    International Normalised Ratio Increased 0/14 (0%) 1/13 (7.7%)
    Lipase Increased 4/14 (28.6%) 4/13 (30.8%)
    Neutrophil Count Decreased 0/14 (0%) 1/13 (7.7%)
    Platelet Count Decreased 1/14 (7.1%) 2/13 (15.4%)
    Weight Decreased 2/14 (14.3%) 3/13 (23.1%)
    Weight Increased 0/14 (0%) 2/13 (15.4%)
    White Blood Cell Count Decreased 0/14 (0%) 1/13 (7.7%)
    Metabolism and nutrition disorders
    Decreased Appetite 5/14 (35.7%) 7/13 (53.8%)
    Dehydration 1/14 (7.1%) 1/13 (7.7%)
    Gout 0/14 (0%) 1/13 (7.7%)
    Hyperammonaemia 0/14 (0%) 1/13 (7.7%)
    Hypercalcaemia 1/14 (7.1%) 0/13 (0%)
    Hyperglycaemia 1/14 (7.1%) 1/13 (7.7%)
    Hyperkalaemia 1/14 (7.1%) 1/13 (7.7%)
    Hypoalbuminaemia 1/14 (7.1%) 1/13 (7.7%)
    Hypocalcaemia 1/14 (7.1%) 1/13 (7.7%)
    Hypoglycaemia 0/14 (0%) 1/13 (7.7%)
    Hypokalaemia 1/14 (7.1%) 1/13 (7.7%)
    Hypomagnesaemia 1/14 (7.1%) 1/13 (7.7%)
    Hyponatraemia 4/14 (28.6%) 2/13 (15.4%)
    Hypophosphataemia 1/14 (7.1%) 2/13 (15.4%)
    Lactic Acidosis 1/14 (7.1%) 0/13 (0%)
    Vitamin D Deficiency 0/14 (0%) 1/13 (7.7%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/14 (7.1%) 1/13 (7.7%)
    Back Pain 1/14 (7.1%) 2/13 (15.4%)
    Flank Pain 1/14 (7.1%) 0/13 (0%)
    Groin Pain 0/14 (0%) 1/13 (7.7%)
    Joint Effusion 0/14 (0%) 1/13 (7.7%)
    Muscle Spasms 1/14 (7.1%) 3/13 (23.1%)
    Muscular Weakness 0/14 (0%) 1/13 (7.7%)
    Musculoskeletal Chest Pain 2/14 (14.3%) 1/13 (7.7%)
    Myalgia 2/14 (14.3%) 0/13 (0%)
    Pain in Extremity 1/14 (7.1%) 1/13 (7.7%)
    Pain in Jaw 0/14 (0%) 1/13 (7.7%)
    Rhabdomyolysis 0/14 (0%) 1/13 (7.7%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lung Squamous Cell Carcinoma Stage Unspecified 0/14 (0%) 1/13 (7.7%)
    Nervous system disorders
    Ataxia 1/14 (7.1%) 0/13 (0%)
    Dizziness 1/14 (7.1%) 3/13 (23.1%)
    Dysarthria 0/14 (0%) 1/13 (7.7%)
    Dysgeusia 0/14 (0%) 1/13 (7.7%)
    Encephalopathy 0/14 (0%) 1/13 (7.7%)
    Headache 6/14 (42.9%) 11/13 (84.6%)
    Neuropathy Peripheral 1/14 (7.1%) 1/13 (7.7%)
    Paraesthesia 1/14 (7.1%) 0/13 (0%)
    Paraplegia 0/14 (0%) 1/13 (7.7%)
    Peripheral Sensory Neuropathy 0/14 (0%) 1/13 (7.7%)
    Spinal Cord Compression 0/14 (0%) 1/13 (7.7%)
    Tremor 0/14 (0%) 1/13 (7.7%)
    Viith Nerve Paralysis 0/14 (0%) 1/13 (7.7%)
    Psychiatric disorders
    Agitation 1/14 (7.1%) 0/13 (0%)
    Anxiety 4/14 (28.6%) 1/13 (7.7%)
    Confusional State 0/14 (0%) 3/13 (23.1%)
    Depression 3/14 (21.4%) 0/13 (0%)
    Insomnia 2/14 (14.3%) 2/13 (15.4%)
    Restlessness 1/14 (7.1%) 0/13 (0%)
    Renal and urinary disorders
    Acute Kidney Injury 0/14 (0%) 2/13 (15.4%)
    Dysuria 2/14 (14.3%) 0/13 (0%)
    Haematuria 1/14 (7.1%) 2/13 (15.4%)
    Pollakiuria 1/14 (7.1%) 0/13 (0%)
    Polyuria 0/14 (0%) 1/13 (7.7%)
    Proteinuria 1/14 (7.1%) 0/13 (0%)
    Urinary Hesitation 0/14 (0%) 1/13 (7.7%)
    Reproductive system and breast disorders
    Testicular Swelling 0/14 (0%) 1/13 (7.7%)
    Respiratory, thoracic and mediastinal disorders
    Aspiration 0/14 (0%) 1/13 (7.7%)
    Chronic Obstructive Pulmonary Disease 0/14 (0%) 1/13 (7.7%)
    Cough 4/14 (28.6%) 3/13 (23.1%)
    Dysphonia 4/14 (28.6%) 1/13 (7.7%)
    Dyspnoea 4/14 (28.6%) 5/13 (38.5%)
    Dyspnoea Exertional 2/14 (14.3%) 0/13 (0%)
    Epistaxis 9/14 (64.3%) 11/13 (84.6%)
    Nasal Congestion 1/14 (7.1%) 0/13 (0%)
    Oropharyngeal Blistering 0/14 (0%) 1/13 (7.7%)
    Oropharyngeal Pain 4/14 (28.6%) 1/13 (7.7%)
    Pleural Effusion 1/14 (7.1%) 3/13 (23.1%)
    Pleuritic Pain 1/14 (7.1%) 0/13 (0%)
    Productive Cough 0/14 (0%) 2/13 (15.4%)
    Pulmonary Embolism 0/14 (0%) 1/13 (7.7%)
    Rhinalgia 0/14 (0%) 1/13 (7.7%)
    Rhinitis Allergic 0/14 (0%) 1/13 (7.7%)
    Sinus Congestion 1/14 (7.1%) 1/13 (7.7%)
    Upper-Airway Cough Syndrome 1/14 (7.1%) 0/13 (0%)
    Wheezing 0/14 (0%) 1/13 (7.7%)
    Skin and subcutaneous tissue disorders
    Alopecia 1/14 (7.1%) 2/13 (15.4%)
    Angioedema 1/14 (7.1%) 0/13 (0%)
    Blood Blister 1/14 (7.1%) 0/13 (0%)
    Dermatitis Acneiform 1/14 (7.1%) 0/13 (0%)
    Dry Skin 1/14 (7.1%) 0/13 (0%)
    Hyperhidrosis 1/14 (7.1%) 0/13 (0%)
    Palmar-Plantar Erythrodysaesthesia Syndrome 6/14 (42.9%) 8/13 (61.5%)
    Photosensitivity Reaction 1/14 (7.1%) 0/13 (0%)
    Pruritus 2/14 (14.3%) 1/13 (7.7%)
    Purpura 0/14 (0%) 1/13 (7.7%)
    Rash 2/14 (14.3%) 4/13 (30.8%)
    Rash Maculo-Papular 5/14 (35.7%) 2/13 (15.4%)
    Seborrhoeic Dermatitis 1/14 (7.1%) 0/13 (0%)
    Skin Abrasion 1/14 (7.1%) 0/13 (0%)
    Skin Discolouration 1/14 (7.1%) 0/13 (0%)
    Skin Lesion 1/14 (7.1%) 1/13 (7.7%)
    Skin Papilloma 0/14 (0%) 1/13 (7.7%)
    Skin Ulcer 0/14 (0%) 1/13 (7.7%)
    Telangiectasia 1/14 (7.1%) 0/13 (0%)
    Urticaria 1/14 (7.1%) 0/13 (0%)
    Vascular disorders
    Flushing 0/14 (0%) 1/13 (7.7%)
    Hypertension 4/14 (28.6%) 8/13 (61.5%)
    Hypotension 1/14 (7.1%) 1/13 (7.7%)

    Limitations/Caveats

    TRC105 development has been discontinued due to lack of efficacy. Secondary endpoints including PFS, OS, duration of response, sorafenib PK, circulating angiogenic biomarkers and assessment of IGF-1-modified Child-Pugh score were not performed.

    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 Charles Theuer
    Organization TRACON Pharmaceuticals Inc.
    Phone (858) 550-0780
    Email ctheuer@traconpharma.com
    Responsible Party:
    Tracon Pharmaceuticals Inc.
    ClinicalTrials.gov Identifier:
    NCT02560779
    Other Study ID Numbers:
    • 105HCC101
    First Posted:
    Sep 25, 2015
    Last Update Posted:
    Jul 17, 2020
    Last Verified:
    Jul 1, 2020