A Phase 3 interventional study of TRC105 and Votrient in Advanced Angiosarcoma, sponsored by Tracon Pharmaceuticals Inc.. Completed at 39 sites in 8 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2020-05-12.
Sponsored by Tracon Pharmaceuticals Inc. · Phase 3, Interventional, and Treatment
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.
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.
99 studies on the registry are indexed under Hemangiosarcoma; 16 are open to participants now.
This study's enrollment of 128 is above the median of 64 across 83 interventional studies indexed under Hemangiosarcoma.
Browse Hemangiosarcoma studies →Tracon Pharmaceuticals Inc. is the lead sponsor of 20 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
weekly TRC105 i.v. in combination with standard dose votrient by mouth, once daily
Biological: TRC105 · Drug: Votrient
standard dose votrient by mouth, once daily
Drug: Votrient
Progression Free Survival of Patients With Unresectable Angiosarcoma
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)
Objective Response Rate of Patients With Unresectable Angiosarcoma
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)
Overall Survival of Patients With Unresectable Angiosarcoma
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)
To Characterize Patient Reported Outcomes Between the Two Arms of the Study
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)
| Milestone | TRC105 + Votrient | Votrient |
|---|---|---|
| Started | 64 | 64 |
| Completed | 64 | 64 |
| Not completed | 0 | 0 |
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.
| months | TRC105 + Votrient | Votrient |
|---|---|---|
| PFS by RECIST 1.1 | 4.2 (2.8 to 8.3) | 4.3 (2.9 to NA) |
| PFS by Investigator Assessment | 3.5 (2.6 to 5.5) | 2.9 (2.6 to 4.1) |
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.
| Participants | TRC105 + Votrient | Votrient |
|---|---|---|
| Objective Response Rate of Patients With Unresectable Angiosarcoma | 3 | 8 |
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)
| Participants | TRC105 + Votrient | Votrient |
|---|---|---|
| Overall Survival of Patients With Unresectable Angiosarcoma | 17 | 19 |
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.
| units on a scale | TRC105 + Votrient | Votrient |
|---|---|---|
| EORTC QLQ-C30 Health Score at Screening | 5 (1 to 7) | 5 (1 to 7) |
| EQ-5D-5L Health Score at Screening | 75 (5 to 100) | 75 (20 to 100) |
| EORTC QLQ-C30 Health Score at Cycle 3 Day 1 | 4 (1 to 6) | 5 (1 to 6) |
| EQ-5D-5L Health Score at Cycle 3 Day 1 | 70 (20 to 100) | 70 (20 to 97) |
Collected over Adverse events were collected over the entire duration of the study (a period of 26 months).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| TRC105 + Votrient | 23/64 (35.9%) | 27/63 (42.9%) | 63/63 (100%) |
| Votrient | 20/64 (31.3%) | 12/57 (21.1%) | 57/57 (100%) |
| Event | TRC105 + Votrient | Votrient |
|---|---|---|
| Disease ProgressionGeneral disorders | 4/63 | 0/57 |
| SepsisInfections and infestations | 0/63 | 3/57 |
| EmbolismVascular disorders | 3/63 | 0/57 |
| FatigueGeneral disorders | 3/63 | 0/57 |
| Wound infectionInfections and infestations | 2/63 | 1/57 |
| PyrexiaGastrointestinal disorders | 1/63 | 1/57 |
| HydropneumothoraxRespiratory, thoracic and mediastinal disorders | 0/63 | 1/57 |
| Mental Status ChangePsychiatric disorders | 0/63 | 1/57 |
| Haemorrhage IntracranialNervous system disorders | 0/63 | 1/57 |
| Tumor HemorrhageNervous system disorders | 0/63 | 1/57 |
| Event | TRC105 + Votrient | Votrient |
|---|---|---|
| EpistaxisRespiratory, thoracic and mediastinal disorders | 44/63 | 4/57 |
| FatigueGeneral disorders | 42/63 | 33/57 |
| HeadacheNervous system disorders | 42/63 | 14/57 |
| DiarrheaGastrointestinal disorders | 38/63 | 31/57 |
| HypertensionVascular disorders | 24/63 | 32/57 |
| NauseaGastrointestinal disorders | 34/63 | 26/57 |
| AnemiaBlood and lymphatic system disorders | 33/63 | 5/57 |
| Decreased AppetiteMetabolism and nutrition disorders | 26/63 | 19/57 |
| VomitingGastrointestinal disorders | 25/63 | 13/57 |
| Weight DecreasedInvestigations | 23/63 | 10/57 |
| Age, Continuous(years) | TRC105 + Votrient | Votrient | Total |
|---|---|---|---|
| Median | 69 (32 to 82) | 67 (25 to 84) | 68 (25 to 84) |
| Sex: Female, Male(Participants) | TRC105 + Votrient | Votrient | Total |
|---|---|---|---|
| Female | 35 | 42 | 77 |
| Male | 29 | 22 | 51 |
| Race/Ethnicity, Customized(Participants) | TRC105 + Votrient | Votrient | Total |
|---|---|---|---|
| Hispanic or Latino | 6 | 3 | 9 |
| Not Hispanic or Latino | 55 | 56 | 111 |
| Not Reported | 1 | 1 | 2 |
| Unknown | 2 | 4 | 6 |
| Region of Enrollment(participants) | TRC105 + Votrient | Votrient | Total |
|---|---|---|---|
| United States | 50 | 46 | 96 |
| Poland | 0 | 4 | 4 |
| United Kingdom | 8 | 9 | 17 |
| France | 6 | 5 | 11 |
| ECOG Performance Status(Participants) | TRC105 + Votrient | Votrient | Total |
|---|---|---|---|
| ECOG Grade 0 | 30 | 27 | 57 |
| ECOG Grade 1 | 32 | 36 | 68 |
| Not Available | 2 | 1 | 3 |
PDFs hosted by the registry, ClinicalTrials.gov.
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Studies of the drug tested here: Carotuximab
Tracon Pharmaceuticals Inc.