TAPPAS: Trial of TRC105 and Pazopanib Versus Pazopanib Alone in Patients With Advanced Angiosarcoma
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
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:
Drug: Votrient
pazopanib
Other Names:
|
Active Comparator: votrient standard dose votrient by mouth, once daily |
Drug: Votrient
pazopanib
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
- 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)
- 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
Inclusion Criteria:
-
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.
-
Documented progression on or following most recent systemic chemotherapy regimen (not required for chemotherapy-naïve patients), within 4 months prior to screening
-
Measurable disease by RECIST v1.1
-
Age of 18 years or older; in addition, patients age 12 to 17 years may enroll beginning in Cohort 2 if weight ≥ 40 kg
-
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
-
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)
-
Adequate organ function
-
Willingness and ability to consent (and assent if under age 18) for self to participate in study
-
Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
-
Angiosarcoma tumor specimen, if available
-
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
-
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:
-
Prior treatment with TRC105
-
Prior treatment with any VEGF inhibitor
-
More than two prior lines (may be combination regimens) of chemotherapy for angiosarcoma (neoadjuvant/adjuvant treatment does not count as a line of treatment)
-
Current treatment or participation on another therapeutic clinical trial
-
Women who are pregnant or breastfeeding
-
Receipt of systemic anticancer therapy, including investigational agents, within 5 times the agent's elimination half-life of starting study treatment
-
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
-
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
-
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.
-
Ascites or pleural effusion requiring intervention or that required intervention or recurred within three months prior to randomization
-
Pericardial effusion (except trace effusion identified by echocardiogram) within three months prior to randomization
-
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
-
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
-
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
-
Hemoptysis (> ½ teaspoon [2.5 mL] of bright red blood) within 6 months prior to randomization
-
Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to randomization
-
Known active viral or nonviral hepatitis or cirrhosis
-
Peptic ulcer within the past 3 months prior to randomization, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD)
-
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
-
Gastrointestinal perforation or fistula in the 6 months prior to randomization unless underlying risk has been resolved (e.g., through surgical resection or repair)
-
Presence of a malabsorption syndrome, gastrointestinal disorder, or gastrointestinal surgery that could affect the absorption of pazopanib
-
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
-
Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
-
Active infection that requires systemic treatment
-
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)
-
History of severe hypersensitivity reaction to any monoclonal antibody
-
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.- 105SAR301
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
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
|
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%
|
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%
|
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
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 |
ctheuer@traconpharma.com |
- 105SAR301