TAPPAS: Trial of TRC105 and Pazopanib Versus Pazopanib Alone in Patients With Advanced Angiosarcoma

Sponsor
Tracon Pharmaceuticals Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02979899
Collaborator
(none)
128
39
2
30.5
3.3
0.1

Study Details

Study Description

Brief Summary

This is a study of TRC105 in combination with standard dose pazopanib compared to single agent pazopanib in patients with angiosarcoma not amenable to curative intent surgery (e.g., metastatic or bulky disease, and disease for which surgical resection would carry an unacceptable risk to the patient) who have not received pazopanib or TRC105 previously.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

TRC105 (carotuximab) is a monoclonal antibody to endoglin (CD105), an essential angiogenic target highly expressed on tumor vessels that is distinct from VEGFR. Endoglin is also expressed directly on tumor cells in angiosarcoma and is upregulated following VEGF inhibition. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical models and complements the activity of bevacizumab and multi-kinase inhibitors that target the VEGFR.

Pazopanib is an oral inhibitor of multiple receptor tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, and VEGFR-3 at therapeutic plasma concentrations. These receptors are implicated in pathologic angiogenesis, tumor growth, and cancer progression.

By targeting a non-VEGF pathway that is upregulated following VEGF inhibition, TRC105 has the potential to complement VEGFR tyrosine kinase inhibitors (TKIs) and could represent a major advance in the treatment of angiosarcoma. Together, the use of TRC105 with pazopanib may result in more effective angiogenesis inhibition and improved clinical efficacy over that seen with pazopanib alone.

Study Design

Study Type:
Interventional
Actual Enrollment :
128 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Phase 3 Trial of TRC105 and Pazopanib Versus Pazopanib Alone in Patients With Advanced Angiosarcoma (TAPPAS)
Actual Study Start Date :
Feb 13, 2017
Actual Primary Completion Date :
Apr 11, 2019
Actual Study Completion Date :
Aug 31, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: TRC105 plus votrient

weekly TRC105 i.v. in combination with standard dose votrient by mouth, once daily

Biological: TRC105
TRC105 antibody
Other Names:
  • anti-endoglin antibody
  • carotuximab
  • Drug: Votrient
    pazopanib
    Other Names:
  • pazopanib
  • Active Comparator: votrient

    standard dose votrient by mouth, once daily

    Drug: Votrient
    pazopanib
    Other Names:
  • pazopanib
  • Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival of Patients With Unresectable Angiosarcoma [from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to cut off date of interim analysis (25 months)]

      Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Progression free survival is defined as time from randomization to either first disease progression (per independent radiology review of images by RECIST 1.1) or death from any cause.

    Secondary Outcome Measures

    1. Objective Response Rate of Patients With Unresectable Angiosarcoma [from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to cut off date of interim analysis (25 months)]

      Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions: Complete Response (CR) is disappearance of all target lesions; Partial Response (PR) is >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Overall response rate is defined as the number of patients with a best response designation of complete response or partial response recorded between the date of randomization and the date of documented progression.

    2. Overall Survival of Patients With Unresectable Angiosarcoma [from beginning of study to cut off date of interim analysis (25 months)]

      Overall survival is the number of death events at 25 months, including all on-study and off-study deaths (past post-treatment 28-day follow up visit)

    3. To Characterize Patient Reported Outcomes Between the Two Arms of the Study [Screening and 9 weeks (Cycle 3 Day 1)]

      Patient reported outcomes as measured by the EuroQol five dimensions questionnaire (EQ-5D-5L) and the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30). The EORTC QLQ-C30 health scale is on a scale of 1 to 7, with 1 being poor health and 7 being excellent health. The EQ-5D-5L scale is on a scale of 0 to 100, with 0 being the worst health one can imagine, and 100 being the best health one can imagine.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Histologically-confirmed angiosarcoma that is not amenable to curative intent surgery (e.g., metastatic or bulky disease and disease for which surgical resection would carry an unacceptable risk to the patient). Pathology report will be reviewed by sponsor prior to randomization.

    2. Documented progression on or following most recent systemic chemotherapy regimen (not required for chemotherapy-naïve patients), within 4 months prior to screening

    3. Measurable disease by RECIST v1.1

    4. Age of 18 years or older; in addition, patients age 12 to 17 years may enroll beginning in Cohort 2 if weight ≥ 40 kg

    5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

    6. Resolution of all acute AEs resulting from prior cancer therapies to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03) grade ≤ 1 or to that patient's pre-study baseline (except alopecia or neuropathy)

    7. Adequate organ function

    8. Willingness and ability to consent (and assent if under age 18) for self to participate in study

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

    10. Angiosarcoma tumor specimen, if available

    11. Men who are sterile (including vasectomy confirmed by post vasectomy semen analysis) OR agree to use a condom with spermicide (refer to Section 2.6.1.3) and to not donate sperm during the study and for at least 180 days following last dose of TRC105 or pazopanib

    12. Woman of non-child bearing potential due to surgical sterilization (at least 6 weeks following surgical bilateral oophorectomy with or without hysterectomy or tubal ligation) confirmed by medical history or menopause (i.e., no menstrual bleeding for more than 12 months in a women aged 45 years or more), 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 acceptable methods of birth control, one of which must be highly effective, during the study and for at least 180 days after stopping TRC105 or pazopanib

    Exclusion Criteria:
    1. Prior treatment with TRC105

    2. Prior treatment with any VEGF inhibitor

    3. More than two prior lines (may be combination regimens) of chemotherapy for angiosarcoma (neoadjuvant/adjuvant treatment does not count as a line of treatment)

    4. Current treatment or participation on another therapeutic clinical trial

    5. Women who are pregnant or breastfeeding

    6. Receipt of systemic anticancer therapy, including investigational agents, within 5 times the agent's elimination half-life of starting study treatment

    7. Major surgical procedure or significant traumatic injury within 4 weeks prior to randomization and must have fully recovered from any such procedure or injury; planned surgery (if applicable) or the anticipated need for a major surgical procedure within the next six months. Note: the following are not considered to be major procedures and are permitted up to 7 days before randomization: Thoracentesis, paracentesis, port placement, laparoscopy, thoracoscopy, tube thoracostomy, bronchoscopy, endoscopic ultrasonographic procedures, mediastinoscopy, skin biopsies, and imaging-guided biopsy for diagnostic purposes

    8. Patients who have received wide field radiotherapy ≤ 28 days (defined as > 50% of volume of pelvic bones or equivalent) or limited field radiation for palliation < 14 days prior to randomization

    9. Uncontrolled hypertension defined as systolic > 150 or diastolic > 100 mm Hg on the average of the 3 most recent BP readings. Anti-hypertensives may be started prior to randomization.

    10. Ascites or pleural effusion requiring intervention or that required intervention or recurred within three months prior to randomization

    11. Pericardial effusion (except trace effusion identified by echocardiogram) within three months prior to randomization

    12. History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease. Patients with radiated or resected lesions are permitted, provided the lesions are fully treated and inactive, patients are asymptomatic, and no steroids have been administered for at least 28 days prior to randomization

    13. Angina, myocardial infarction, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism , pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) within 6 months prior to randomization. Deep venous thrombosis within 3 months prior to randomization unrelated to a central venous catheter, unless the patient is anti-coagulated without the use of warfarin for at least 2 weeks prior to randomization. In this situation, low molecular weight heparin is preferred

    14. Active bleeding or pathologic condition that carries a high risk of bleeding (e.g., hereditary hemorrhagic telangiectasia). Patients with bleeding cutaneous lesions not actively requiring transfusions are eligible. Patients who have been uneventfully anti-coagulated with low molecular weight heparin are eligible

    15. Hemoptysis (> ½ teaspoon [2.5 mL] of bright red blood) within 6 months prior to randomization

    16. Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to randomization

    17. Known active viral or nonviral hepatitis or cirrhosis

    18. Peptic ulcer within the past 3 months prior to randomization, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD)

    19. Presence of tumor(s) invading into the heart or great vessels (including carotid artery) or another location where bleeding is associated with high morbidity including patients with primary cardiac or great vessel angiosarcoma

    20. Gastrointestinal perforation or fistula in the 6 months prior to randomization unless underlying risk has been resolved (e.g., through surgical resection or repair)

    21. Presence of a malabsorption syndrome, gastrointestinal disorder, or gastrointestinal surgery that could affect the absorption of pazopanib

    22. History of prior malignancy except adequately treated basal cell or squamous cell skin cancer or adequately treated, with curative intent, cancer from which the patient is currently in complete remission per Investigator's judgment; patients with history of breast cancer and no evidence of disease on hormonal therapy to prevent recurrence and patients with prostate cancer on adjuvant hormonal therapy with undetectable PSA are eligible

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

    24. Active infection that requires systemic treatment

    25. Concurrent use or receipt of a strong CYP3A4 inducer within 12 days prior to randomization or a strong CYP3A4 inhibitor within 7 days prior to randomization (see Table 10)

    26. History of severe hypersensitivity reaction to any monoclonal antibody

    27. Other severe acute or chronic medical (including bone marrow suppressive diseases) or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation, impede the ability of the patient to complete all protocol-specified activities, or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for this study

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Arizona Cancer Center Tucson Arizona United States 85724
    2 Stanford University Palo Alto California United States 94304
    3 Sarcoma Oncology Center Santa Monica California United States 90403
    4 University of Colorado Denver Aurora Colorado United States 80045
    5 Mayo Clinic Jacksonville Jacksonville Florida United States 32224
    6 Moffitt Cancer Center Tampa Florida United States 33612
    7 Northside Hospital Sandy Springs Georgia United States 30342
    8 University of Iowa Iowa City Iowa United States 52242
    9 Johns Hopkins Baltimore Maryland United States 21231
    10 Massachusetts General Hospital Boston Massachusetts United States 02114
    11 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    12 Mayo Clinic Rochester Rochester Minnesota United States 55905
    13 Washington University St. Louis Saint Louis Missouri United States 63110
    14 Roswell Park Cancer Institute Buffalo New York United States 14263
    15 Northwell Health Lake Success New York United States 11042
    16 MSKCC New York New York United States 10017
    17 Duke University Durham North Carolina United States 27705
    18 Cleveland Clinic Cleveland Ohio United States 44195
    19 Ohio State University Columbus Ohio United States 43202
    20 Thomas Jefferson University Philadelphia Pennsylvania United States 19107
    21 UPMC Pittsburgh Pennsylvania United States 15232
    22 Vanderbilt University Nashville Tennessee United States 37212
    23 MD Anderson Houston Texas United States 77230
    24 University of Utah, Huntsman Cancer Institute Salt Lake City Utah United States 84112
    25 University of Washinton Seattle Washington United States 98109
    26 Medical College of Wisconsin Milwaukee Wisconsin United States 53226
    27 Medical University,Vienna Wien Austria
    28 Institut Bergonié Bordeaux France
    29 Centre Oscar Lambret Lille France
    30 Centre Léon Bérard Lyon France
    31 Institut Gustave Roussy Villejuif France
    32 Helios Klinikum Bad Saarow Germany
    33 Mannheim University Medical Center Mannheim Germany
    34 Klinikum derUniversitat Munchen Munich Germany
    35 Fondazione IRCCS Istituto Nazionale dei Tumori Milano Italy
    36 Memorial Cancer Center and Institute of Oncology Warszawa Poland
    37 Institut Català d'Oncologia (ICO) Barcelona Spain
    38 12 de Octubre University Hospital Madrid Spain
    39 Royal Marsden NHS Chelsea United Kingdom

    Sponsors and Collaborators

    • Tracon Pharmaceuticals Inc.

    Investigators

    • Study Director: Charles Theuer, MD, TRACON Pharmaceuticals

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Tracon Pharmaceuticals Inc.
    ClinicalTrials.gov Identifier:
    NCT02979899
    Other Study ID Numbers:
    • 105SAR301
    First Posted:
    Dec 2, 2016
    Last Update Posted:
    May 12, 2020
    Last Verified:
    May 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Tracon Pharmaceuticals Inc.
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title TRC105 + Votrient Votrient
    Arm/Group Description Weekly TRC105 i.v. in combination with standard dose votrient by mouth, once daily TRC105: TRC105 antibody Votrient: pazopanib Standard dose votrient by mouth, once daily Votrient: pazopanib
    Period Title: Overall Study
    STARTED 64 64
    COMPLETED 64 64
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title TRC105 + Votrient Votrient Total
    Arm/Group Description Weekly TRC105 i.v. in combination with standard dose votrient by mouth, once daily TRC105: TRC105 antibody Votrient: pazopanib Standard dose votrient by mouth, once daily Votrient: pazopanib Total of all reporting groups
    Overall Participants 64 64 128
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    69
    67
    68
    Sex: Female, Male (Count of Participants)
    Female
    35
    54.7%
    42
    65.6%
    77
    60.2%
    Male
    29
    45.3%
    22
    34.4%
    51
    39.8%
    Race/Ethnicity, Customized (Count of Participants)
    Hispanic or Latino
    6
    9.4%
    3
    4.7%
    9
    7%
    Not Hispanic or Latino
    55
    85.9%
    56
    87.5%
    111
    86.7%
    Not Reported
    1
    1.6%
    1
    1.6%
    2
    1.6%
    Unknown
    2
    3.1%
    4
    6.3%
    6
    4.7%
    Region of Enrollment (participants) [Number]
    United States
    50
    78.1%
    46
    71.9%
    96
    75%
    Poland
    0
    0%
    4
    6.3%
    4
    3.1%
    United Kingdom
    8
    12.5%
    9
    14.1%
    17
    13.3%
    France
    6
    9.4%
    5
    7.8%
    11
    8.6%
    ECOG Performance Status (Count of Participants)
    ECOG Grade 0
    30
    46.9%
    27
    42.2%
    57
    44.5%
    ECOG Grade 1
    32
    50%
    36
    56.3%
    68
    53.1%
    Not Available
    2
    3.1%
    1
    1.6%
    3
    2.3%

    Outcome Measures

    1. Primary Outcome
    Title Progression Free Survival of Patients With Unresectable Angiosarcoma
    Description Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Progression free survival is defined as time from randomization to either first disease progression (per independent radiology review of images by RECIST 1.1) or death from any cause.
    Time Frame from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to cut off date of interim analysis (25 months)

    Outcome Measure Data

    Analysis Population Description
    All patients randomized onto study by cut off date of interim analysis
    Arm/Group Title TRC105 + Votrient Votrient
    Arm/Group Description Weekly TRC105 i.v. in combination with standard dose votrient by mouth, once daily TRC105: TRC105 antibody Votrient: pazopanib Standard dose votrient by mouth, once daily Votrient: pazopanib
    Measure Participants 62 61
    PFS by RECIST 1.1
    4.2
    4.3
    PFS by Investigator Assessment
    3.5
    2.9
    2. Secondary Outcome
    Title Objective Response Rate of Patients With Unresectable Angiosarcoma
    Description Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions: Complete Response (CR) is disappearance of all target lesions; Partial Response (PR) is >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Overall response rate is defined as the number of patients with a best response designation of complete response or partial response recorded between the date of randomization and the date of documented progression.
    Time Frame from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to cut off date of interim analysis (25 months)

    Outcome Measure Data

    Analysis Population Description
    All patients randomized onto study by cut off date of interim analysis
    Arm/Group Title TRC105 + Votrient Votrient
    Arm/Group Description Weekly TRC105 i.v. in combination with standard dose votrient by mouth, once daily TRC105: TRC105 antibody Votrient: pazopanib Standard dose votrient by mouth, once daily Votrient: pazopanib
    Measure Participants 62 61
    Count of Participants [Participants]
    3
    4.7%
    8
    12.5%
    3. Secondary Outcome
    Title Overall Survival of Patients With Unresectable Angiosarcoma
    Description Overall survival is the number of death events at 25 months, including all on-study and off-study deaths (past post-treatment 28-day follow up visit)
    Time Frame from beginning of study to cut off date of interim analysis (25 months)

    Outcome Measure Data

    Analysis Population Description
    All patients randomized onto study by cut off date of interim analysis
    Arm/Group Title TRC105 + Votrient Votrient
    Arm/Group Description Weekly TRC105 i.v. in combination with standard dose votrient by mouth, once daily TRC105: TRC105 antibody Votrient: pazopanib Standard dose votrient by mouth, once daily Votrient: pazopanib
    Measure Participants 62 61
    Count of Participants [Participants]
    17
    26.6%
    19
    29.7%
    4. Secondary Outcome
    Title To Characterize Patient Reported Outcomes Between the Two Arms of the Study
    Description Patient reported outcomes as measured by the EuroQol five dimensions questionnaire (EQ-5D-5L) and the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30). The EORTC QLQ-C30 health scale is on a scale of 1 to 7, with 1 being poor health and 7 being excellent health. The EQ-5D-5L scale is on a scale of 0 to 100, with 0 being the worst health one can imagine, and 100 being the best health one can imagine.
    Time Frame Screening and 9 weeks (Cycle 3 Day 1)

    Outcome Measure Data

    Analysis Population Description
    All patients who completed the questionnaire during specified intervals listed below
    Arm/Group Title TRC105 + Votrient Votrient
    Arm/Group Description Weekly TRC105 i.v. in combination with standard dose votrient by mouth, once daily TRC105: TRC105 antibody Votrient: pazopanib Standard dose votrient by mouth, once daily Votrient: pazopanib
    Measure Participants 64 62
    EORTC QLQ-C30 Health Score at Screening
    5
    5
    EQ-5D-5L Health Score at Screening
    75
    75
    EORTC QLQ-C30 Health Score at Cycle 3 Day 1
    4
    5
    EQ-5D-5L Health Score at Cycle 3 Day 1
    70
    70

    Adverse Events

    Time Frame Adverse events were collected over the entire duration of the study (a period of 26 months).
    Adverse Event Reporting Description AEs were collected for each patient that received at least 1 dose of study drug from informed consent through 28 days following the last dose of study drug. Related AEs were followed until they resolved or became stable. All-Cause Mortality was monitored in all randomized participants as overall survival (OS) was a secondary endpoint of the study. OS was followed until death regardless of subsequent treatment. Patients were eligible for participation in the trial until they progressed.
    Arm/Group Title TRC105 + Votrient Votrient
    Arm/Group Description All patients that received at least one dose of TRC105 in combination with pazopanib All patients that received at least one dose of pazopanib alone.
    All Cause Mortality
    TRC105 + Votrient Votrient
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 23/64 (35.9%) 20/64 (31.3%)
    Serious Adverse Events
    TRC105 + Votrient Votrient
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 27/63 (42.9%) 12/57 (21.1%)
    Blood and lymphatic system disorders
    Platelet Disorder 0/63 (0%) 1/57 (1.8%)
    Anemia 1/63 (1.6%) 0/57 (0%)
    Cardiac disorders
    Myocardial Infarction 1/63 (1.6%) 0/57 (0%)
    Cardiac Failure 1/63 (1.6%) 0/57 (0%)
    Eye disorders
    Retinal Detachment 1/63 (1.6%) 0/57 (0%)
    Gastrointestinal disorders
    Pyrexia 1/63 (1.6%) 1/57 (1.8%)
    Upper Gastrointestinal Hemorrhage 1/63 (1.6%) 0/57 (0%)
    Proctalgia 1/63 (1.6%) 0/57 (0%)
    Pancreatitis 1/63 (1.6%) 0/57 (0%)
    Nausea 1/63 (1.6%) 0/57 (0%)
    Hematemesis 1/63 (1.6%) 0/57 (0%)
    Gastrointestinal Hemorrhage 1/63 (1.6%) 0/57 (0%)
    General disorders
    Disease Progression 4/63 (6.3%) 0/57 (0%)
    Fatigue 3/63 (4.8%) 0/57 (0%)
    Multi-Organ Failure 0/63 (0%) 1/57 (1.8%)
    Chest Pain 1/63 (1.6%) 0/57 (0%)
    Hepatobiliary disorders
    Acute Hepatic Failure 0/63 (0%) 1/57 (1.8%)
    Infections and infestations
    Wound infection 2/63 (3.2%) 1/57 (1.8%)
    Sepsis 0/63 (0%) 3/57 (5.3%)
    Urinary Tract Infection 1/63 (1.6%) 0/57 (0%)
    Osteomyelitis 1/63 (1.6%) 0/57 (0%)
    Meningitis Aseptic 1/63 (1.6%) 0/57 (0%)
    Influenza 1/63 (1.6%) 0/57 (0%)
    Bacteremia 1/63 (1.6%) 0/57 (0%)
    Injury, poisoning and procedural complications
    Subdural Hematoma 1/63 (1.6%) 0/57 (0%)
    Rib Fracture 1/63 (1.6%) 0/57 (0%)
    Infusion Related Reaction 1/63 (1.6%) 0/57 (0%)
    Fall 0/63 (0%) 1/57 (1.8%)
    Clavicle Fracture 1/63 (1.6%) 0/57 (0%)
    Investigations
    Aspartate Aminotransferase Increased 0/63 (0%) 1/57 (1.8%)
    Alanine Aminotransferase Increased 0/63 (0%) 1/57 (1.8%)
    Metabolism and nutrition disorders
    Tumor Lysis Syndrome 1/63 (1.6%) 0/57 (0%)
    Hyponatremia 1/63 (1.6%) 0/57 (0%)
    Failure To Thrive 0/63 (0%) 1/57 (1.8%)
    Dehydration 1/63 (1.6%) 0/57 (0%)
    Musculoskeletal and connective tissue disorders
    Musculoskeletal Chest Pain 0/63 (0%) 1/57 (1.8%)
    Nervous system disorders
    Headache 1/63 (1.6%) 0/57 (0%)
    Haemorrhage Intracranial 0/63 (0%) 1/57 (1.8%)
    Encephalopathy 1/63 (1.6%) 0/57 (0%)
    Tumor Hemorrhage 0/63 (0%) 1/57 (1.8%)
    Psychiatric disorders
    Mental Status Change 0/63 (0%) 1/57 (1.8%)
    Respiratory, thoracic and mediastinal disorders
    Respiratory Failure 1/63 (1.6%) 0/57 (0%)
    Respiratory Distress 1/63 (1.6%) 0/57 (0%)
    Pneumonitis 1/63 (1.6%) 0/57 (0%)
    Pleural Effusion 1/63 (1.6%) 0/57 (0%)
    Hypoxia 1/63 (1.6%) 0/57 (0%)
    Hydropneumothorax 0/63 (0%) 1/57 (1.8%)
    Dyspnea 1/63 (1.6%) 0/57 (0%)
    Vascular disorders
    Embolism 3/63 (4.8%) 0/57 (0%)
    Other (Not Including Serious) Adverse Events
    TRC105 + Votrient Votrient
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 63/63 (100%) 57/57 (100%)
    Blood and lymphatic system disorders
    Anemia 33/63 (52.4%) 5/57 (8.8%)
    Thrombocytopenia 3/63 (4.8%) 3/57 (5.3%)
    Cardiac disorders
    Sinus Tachycardia 3/63 (4.8%) 3/57 (5.3%)
    Bradycardia 4/63 (6.3%) 0/57 (0%)
    Tachycardia 3/63 (4.8%) 1/57 (1.8%)
    Endocrine disorders
    Hypothyroidism 11/63 (17.5%) 5/57 (8.8%)
    Hyperthyroidism 3/63 (4.8%) 1/57 (1.8%)
    Eye disorders
    Vision Blurred 6/63 (9.5%) 5/57 (8.8%)
    Lacrimation Increased 4/63 (6.3%) 0/57 (0%)
    Gastrointestinal disorders
    Diarrhea 38/63 (60.3%) 31/57 (54.4%)
    Nausea 34/63 (54%) 26/57 (45.6%)
    Vomiting 25/63 (39.7%) 13/57 (22.8%)
    Abdominal Pain 14/63 (22.2%) 10/57 (17.5%)
    Constipation 13/63 (20.6%) 9/57 (15.8%)
    Stomatitis 16/63 (25.4%) 5/57 (8.8%)
    Gingival Bleeding 17/63 (27%) 2/57 (3.5%)
    Dyspepsia 7/63 (11.1%) 5/57 (8.8%)
    Abdominal Pain Upper 6/63 (9.5%) 3/57 (5.3%)
    Dry Mouth 6/63 (9.5%) 3/57 (5.3%)
    Mouth Hemorrhage 7/63 (11.1%) 0/57 (0%)
    Oral Pain 6/63 (9.5%) 1/57 (1.8%)
    Gastrooesophageal Reflux Disease 3/63 (4.8%) 4/57 (7%)
    Flatulence 2/63 (3.2%) 5/57 (8.8%)
    Abdominal Distension 2/63 (3.2%) 3/57 (5.3%)
    Gingival Pain 4/63 (6.3%) 0/57 (0%)
    Hematemesis 4/63 (6.3%) 0/57 (0%)
    Oral Dysesthesia 3/63 (4.8%) 2/57 (3.5%)
    Hemorrhoids 3/63 (4.8%) 1/57 (1.8%)
    General disorders
    Fatigue 42/63 (66.7%) 33/57 (57.9%)
    Edema Peripheral 13/63 (20.6%) 6/57 (10.5%)
    Pyrexia 11/63 (17.5%) 4/57 (7%)
    Chills 10/63 (15.9%) 4/57 (7%)
    Mucosal Inflammation 7/63 (11.1%) 4/57 (7%)
    Asthenia 7/63 (11.1%) 2/57 (3.5%)
    Pain 5/63 (7.9%) 1/57 (1.8%)
    Chest Pain 4/63 (6.3%) 1/57 (1.8%)
    Disease Progression 4/63 (6.3%) 0/57 (0%)
    Non-Cardiac Chest Pain 3/63 (4.8%) 2/57 (3.5%)
    Facial Pain 3/63 (4.8%) 1/57 (1.8%)
    Hepatobiliary disorders
    Hyperbilirubinemia 2/63 (3.2%) 3/57 (5.3%)
    Infections and infestations
    Urinary Tract Infection 9/63 (14.3%) 2/57 (3.5%)
    Sepsis 0/63 (0%) 3/57 (5.3%)
    Injury, poisoning and procedural complications
    Infusion Related Reaction 8/63 (12.7%) 1/57 (1.8%)
    Fall 5/63 (7.9%) 3/57 (5.3%)
    Investigations
    Weight Decreased 23/63 (36.5%) 10/57 (17.5%)
    Aspartate Aminotransferase Increased 16/63 (25.4%) 14/57 (24.6%)
    Alanine Aminotransferase Increased 15/63 (23.8%) 12/57 (21.1%)
    Platelet Count Decreased 9/63 (14.3%) 7/57 (12.3%)
    Lipase Increased 9/63 (14.3%) 6/57 (10.5%)
    Blood Bilirubin Increased 6/63 (9.5%) 9/57 (15.8%)
    Blood Thyroid Stimulating Hormone Increased 6/63 (9.5%) 4/57 (7%)
    Neutrophil Count Decreased 5/63 (7.9%) 4/57 (7%)
    Blood Alkaline Phosphatase Increased 7/63 (11.1%) 1/57 (1.8%)
    Lymphocyte Count Decreased 7/63 (11.1%) 1/57 (1.8%)
    Blood Creatinine Increased 3/63 (4.8%) 4/57 (7%)
    White Blood Cell Count Decreased 4/63 (6.3%) 2/57 (3.5%)
    Blood Amylase Increased 3/63 (4.8%) 3/57 (5.3%)
    Metabolism and nutrition disorders
    Decreased Appetite 26/63 (41.3%) 19/57 (33.3%)
    Hypokalemia 14/63 (22.2%) 4/57 (7%)
    Dehydration 10/63 (15.9%) 3/57 (5.3%)
    Hypoalbuminaemia 9/63 (14.3%) 1/57 (1.8%)
    Hypomagnesaemia 7/63 (11.1%) 3/57 (5.3%)
    Hyponatraemia 6/63 (9.5%) 3/57 (5.3%)
    Hyperglycemia 5/63 (7.9%) 3/57 (5.3%)
    Hypocalcaemia 5/63 (7.9%) 0/57 (0%)
    Hypoxia 4/63 (6.3%) 1/57 (1.8%)
    Hyperkalemia 4/63 (6.3%) 0/57 (0%)
    Hypophosphatemia 3/63 (4.8%) 1/57 (1.8%)
    Musculoskeletal and connective tissue disorders
    Back Pain 13/63 (20.6%) 6/57 (10.5%)
    Myalgia 8/63 (12.7%) 6/57 (10.5%)
    Arthralgia 7/63 (11.1%) 5/57 (8.8%)
    Muscular Weakness 3/63 (4.8%) 6/57 (10.5%)
    Musculoskeletal Pain 5/63 (7.9%) 3/57 (5.3%)
    Muscle Spasms 5/63 (7.9%) 2/57 (3.5%)
    Pain In Extremity 2/63 (3.2%) 5/57 (8.8%)
    Musculoskeletal Chest Pain 4/63 (6.3%) 1/57 (1.8%)
    Pain In Jaw 4/63 (6.3%) 0/57 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumor Pain 4/63 (6.3%) 4/57 (7%)
    Nervous system disorders
    Headache 42/63 (66.7%) 14/57 (24.6%)
    Dysgeusia 15/63 (23.8%) 15/57 (26.3%)
    Dizziness 7/63 (11.1%) 3/57 (5.3%)
    Migraine 4/63 (6.3%) 0/57 (0%)
    Psychiatric disorders
    Anxiety 6/63 (9.5%) 5/57 (8.8%)
    Insomnia 7/63 (11.1%) 3/57 (5.3%)
    Depression 3/63 (4.8%) 1/57 (1.8%)
    Renal and urinary disorders
    Proteinuria 3/63 (4.8%) 5/57 (8.8%)
    Hematuria 3/63 (4.8%) 1/57 (1.8%)
    Respiratory, thoracic and mediastinal disorders
    Epistaxis 44/63 (69.8%) 4/57 (7%)
    Dyspnea 16/63 (25.4%) 6/57 (10.5%)
    Oropharyngeal Pain 5/63 (7.9%) 6/57 (10.5%)
    Cough 5/63 (7.9%) 5/57 (8.8%)
    Dysphonia 5/63 (7.9%) 4/57 (7%)
    Pleural effusion 5/63 (7.9%) 1/57 (1.8%)
    Nasal Congestion 4/63 (6.3%) 0/57 (0%)
    Skin and subcutaneous tissue disorders
    Palmar-Plantar Erythrodysaesthesia Syndrome 9/63 (14.3%) 9/57 (15.8%)
    Pruritus 4/63 (6.3%) 4/57 (7%)
    Dry Skin 3/63 (4.8%) 5/57 (8.8%)
    Erythema 4/63 (6.3%) 3/57 (5.3%)
    Rash 5/63 (7.9%) 1/57 (1.8%)
    Rash Maculo-Papular 5/63 (7.9%) 1/57 (1.8%)
    Alopecia 3/63 (4.8%) 3/57 (5.3%)
    Telangiectasia 5/63 (7.9%) 0/57 (0%)
    Skin Lesion 1/63 (1.6%) 3/57 (5.3%)
    Pain Of Skin 3/63 (4.8%) 1/57 (1.8%)
    Vascular disorders
    Hypertension 24/63 (38.1%) 32/57 (56.1%)
    Hypotension 11/63 (17.5%) 3/57 (5.3%)
    Flushing 11/63 (17.5%) 1/57 (1.8%)
    Embolism 6/63 (9.5%) 0/57 (0%)

    Limitations/Caveats

    [Not Specified]

    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, Medical Monitor
    Organization TRACON Pharmaceuticals Inc
    Phone 8585500780
    Email ctheuer@traconpharma.com
    Responsible Party:
    Tracon Pharmaceuticals Inc.
    ClinicalTrials.gov Identifier:
    NCT02979899
    Other Study ID Numbers:
    • 105SAR301
    First Posted:
    Dec 2, 2016
    Last Update Posted:
    May 12, 2020
    Last Verified:
    May 1, 2020