Advanced Soft Tissue SarcomaPhase 1/2NCT01975519
A Phase 1B Dose-escalation and Phase 2a Study of Carotuximab (TRC105) in Combination With Pazopanib in Patients With Advanced Soft Tissue Sarcoma
A Phase 1/2 study testing TRC105 and Pazopanib in people with Advanced Soft Tissue Sarcoma, run by Tracon Pharmaceuticals Inc. at 9 sites in United States.
Trial 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 pazopanib in patients with advanced soft tissue sarcoma. Up to 30 patients will be treated. Read more about this study
- Who is it for?
- Ages 12 to 120 years
- Conditions the study is for
- Advanced Soft Tissue Sarcoma
- What is being tested?
- TRC105 and Pazopanib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 111 participants
- Where
- 9 sitesUnited States
- Study dates
- 10 Dec 2013to 11 Mar 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 120 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Histologically confirmed unresectable soft tissue sarcoma that has progressed following treatment with chemotherapy. Prior pazopanib is allowed if the drug was not discontinued for toxicity ( Phase 1b only)
- Histologically confirmed metastatic soft tissue sarcoma that has progressed by RECIST following treatment with anthracycline chemotherapy. Patients may have received up to four lines of systemic therapy for metastatic disease and no more than two lines of combination treatment ( Phase 2 only)
- Histologically confirmed locally advanced (e.g. unresectable) or metastatic angiosarcoma that has progressed following treatment with prior systemic therapy. Progression must be documented on or following the most recent systemic therapy. Prior pazopanib is allowed if the drug was not discontinued for toxicity (Phase 2 angiosarcoma cohorts only)
- Measurable disease by RECIST
- Age of 12 years or older (patient must weigh ≥ 40 kg)
- ECOG performance status ≤ 1
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- Resolution of all acute adverse events resulting from prior cancer therapies to NCI CTCAE grade ≤ 1 or baseline (except alopecia or neuropathy)
- Adequate organ function.
- Willingness and ability to consent for self to participate in study
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
- Available archival tumor specimen of the soft tissue sarcoma that meets inclusion criterion #1, #2 or #3
Who cannot join
- Prior treatment with TRC105
- Prior treatment with a VEGFR TKI (including pazopanib) (Phase 2 only)
- Current treatment on another therapeutic clinical trial
- Receipt of systemic anticancer therapy, including investigational agents, within 28 days of starting study treatment.
- No major surgical procedure or significant traumatic injury within 6 weeks prior to study registration, and must have fully recovered from any such procedure; date of surgery (if applicable) or the anticipated need for a major surgical procedure within the next six months.
- Patients who have received wide field radiotherapy ≤ 28 days or limited field radiation for palliation < 14 days prior to cycle 1 day 1 or those patients who have not recovered adequately from side effects of such therapy
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- Uncontrolled chronic hypertension
- Significant ascites or pericardial or pleural effusion
- History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
- Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, PTCA or CABG within the past 6 months. Deep venous thrombosis within 6 months, unless the patient is anti-coagulated without the use of warfarin for at least 2 weeks. In this situation, low molecular weight heparin is preferred.
- Active bleeding or pathologic condition that carries a high risk of bleeding. Patients who have been uneventfully anti-coagulated with low molecular weight heparin are eligible.
- Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy
- Known active viral or nonviral hepatitis or cirrhosis
- History of hemorrhage or hemoptysis within 3 months of starting study treatment
- History of peptic ulcer within the past 3 months of treatment
- History of gastrointestinal perforation or fistula in the past 6 months, or while previously on antiangiogenic therapy, unless underlying risk has been resolved
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
- Receipt of a strong CYP3A4 inducer within 12 days prior to cycle 1 day 1 or a strong CYP3A4 inhibitor within 7 days prior to cycle 1 day 1.
- Pregnancy or breastfeeding. Female patients must be surgically sterile (i.e.: hysterectomy) or be postmenopausal, or must agree to use effective contraception during the study and for 3 months following last dose of TRC105. All female patients of reproductive potential must have a negative pregnancy test (serum or urine) within 7 days prior to first dose. Male patients must be surgically sterile or must agree to use effective contraception during the study and for 3 months following last dose of TRC105. The definition of effective contraception will be based on the judgment of the Principal Investigator or a designated associate.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for this study.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35243
Roswell Park Cancer Institute
Buffalo, New York, 92122
Mary Crowley Cancer Research Center
Dallas, Texas, 75230
Duke University
Durham, North Carolina, 27710
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224
Mount Sinai School of Medicine-Tisch Cancer Institute
New York, New York, 10029
Mayo Clinic Rochester
Rochester, Minnesota, 55905
University of Utah
Salt Lake City, Utah, 84112
Sarcoma Oncology Center
Santa Monica, California, 90403
About this study
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 pazopanib in patients with advanced soft tissue sarcoma. Up to 30 patients will be treated.
The purpose of the phase 2 portion is to estimate the PFS of patients with advanced soft tissue sarcoma by RECIST 1.1 and estimate ORR in a separate cohort of patients with angiosarcoma by RECIST 1.1. Up to 89 patients will be treated in phase 2, including two cohorts of up to 13 patients with angiosarcoma.
Read the detailed description
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. Pazopanib is approved for the treatment of advanced soft tissue sarcoma, following progression on one prior systemic therapy, based on improved progression free survival. TRC105 is an antibody to CD105, an important angiogenic target on vascular endothelial cells that is distinct from VEGFR. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical models and complements the activity of bevacizumab and multi-kinase inhibitors that target the VEGFR. In a phase 1 study of advanced solid tumors, TRC105 therapy caused a global reduction in angiogenic biomarkers and reduced tumor burden at doses that were well-tolerated. In a phase 1b study, the combination of TRC105 and bevacizumab produced radiographic reductions in tumor volume in bevacizumab-refractory patients, and was well tolerated. TRC105 potentiates bevacizumab and VEGFR tyrosine kinases (VEGFR TKI) in preclinical models. By targeting a non-VEGF pathway that is upregulated following VEGF inhibition, TRC105 has the potential to complement VEGFR TKIs and could represent a major advance in cancer therapy. Together, the use of TRC105 with pazopanib may result in more effective angiogenesis inhibition and improved clinical efficacy over that seen with pazopanib alone.
- Conditions
- Advanced Soft Tissue Sarcoma
- Being tested
- TRC105 and Pazopanib
- Keywords
- TRC105, CD105, Endoglin, Angiogenesis Inhibitor, STS, Soft Tissue Sarcoma, TKI, Tyrosine Kinase Inhibitor, Pazopanib, Votrient, Advanced Soft Tissue Sarcoma, Angiosarcoma
- Medical subject headings
- Sarcoma, Hemangiosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TRC105 and PazopanibDrug
Also called Chimeric Antibody (TRC105) to CD105, Votrient
Weekly TRC105 in combination with standard dose Pazopanib.
| Study group | Role | What they receive |
|---|---|---|
| TRC105 and Pazopanib | Experimental | Weekly TRC105 in combination with standard dose pazopanib or every two week administration during cycle 1, and starting on cycle 2 day 1 and beyond, TRC105 may be administered every two weeks. This is also in combination with standard dose pazopanib. Receives: Drug: TRC105 and Pazopanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicity (DLT)
For DLT evaluation, severity (grade) was classified according to common terminology criteria for adverse events version 4.0 (CTCAE v4.0). DLTs were defined as grade 4 neutropenia persisting for ≥ 5 days, febrile neutropenia (grade 4 neutropenia with fever > 38.5 ºC both sustained over a 24 hour period), neutropenic infection (grade ≥ 3 neutropenia with grade ≥ 3 infection), anemia ≥ grade 4, grade > 4 thrombocytopenia or grade ≥ 3 thrombocytopenia and grade ≥ 3 hemorrhage, or grade 3 or 4 nonhematologic toxicity with the following exceptions: nausea, vomiting, or diarrhea for <48 hours, asymptomatic electrolyte abnormalities that are corrected to grade 1 or better in < 72 hours, or headache lasting less than 48 hours.
Measured: 56 days
Progression Free Survival of Patients With Advanced Soft Tissue Sarcoma (Phase 1 and 2)
Number of patients with progression free survival, as defined as time from screening to either first disease progression or death from any cause per RECIST version 1.1
Measured: from screening to either disease progression or death
Objective Response Rate in a Cohort of Patients With Angiosarcoma
The best response according to RECIST 1.1 for each patient in the phase 2 angiosarcoma cohort with measurable disease and who received at least one dose of study drug will be listed by cohort and tumor type
Measured: 1.5 years
Secondary outcomes (5)
Trough Concentrations of TRC105 (Phase 2)
Trough serum TRC105 concentrations will be measured using validated ELISA methods.
Measured: 4, 6, 8, and 10 weeks
Number of Patients With and Without Development of Immunogenicity Antibodies (Phase 1 and 2)
Anti-product antibody concentrations will be measured using validated ELISA methods. Anti-product antibody concentrations will be evaluated in the context of pharmacokinetic parameters and AE profiles.
Measured: 32 months
Number of Patients With and Without Expression of Endoglin on Sarcoma Tissue (Phase 1 and 2)
Expression will be determined by immunohistochemistry for each patient who received at least one dose of TRC105
Measured: 12 months
Objective Response Rate in Patients With Advanced Soft Tissue Sarcoma by RECIST 1.1
The best response (CR, PR, SD or PD according to RECIST 1.1) for each patient (phase 1 and phase 2) with measurable disease who received at least one dose of TRC105 study drug
Measured: 12 months
Progression Free Survival in a Cohort of Patients With Angiosarcoma (Phase 2)
Time from screening to either first disease progression or death from any cause per RECIST version 1.1
Measured: 26 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2013 (estimated)
- Study start10 Dec 2013
- Primary completion11 Mar 2019
- Study completion11 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced Soft Tissue SarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 111 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tracon Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Charles Theuer, MD, Study director, Tracon Pharmaceuticals Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01975519
- Sponsor's protocol ID
- 105SAR101
- Status last verified
- May 2020
- First submitted
- 23 Oct 2013
- Last updated
- 20 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1B Dose-escalation and Phase 2a Study of Carotuximab (TRC105) in Combination With Pazopanib in Patients With Advanced Soft Tissue Sarcoma
- ClinicalTrials.gov ID
- NCT01975519
- Acronym / sponsor ID
- 105SAR101
- Conditions
- Advanced Soft Tissue Sarcoma
- Keywords
- TRC105, CD105, Endoglin, Angiogenesis Inhibitor, STS, Soft Tissue Sarcoma, TKI, Tyrosine Kinase Inhibitor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 111 participants (actual)
- Lead sponsor
- Tracon Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- 10 Dec 2013 (actual)
- Primary completion
- 11 Mar 2019 (actual)
- Study completion
- 11 Mar 2019 (actual)
- First posted
- 4 Nov 2013 (estimated)
- Results
- Posted 12 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 pazopanib in patients with advanced soft tissue sarcoma. Up to 30 patients will be treated.
The purpose of the phase 2 portion is to estimate the PFS of patients with advanced soft tissue sarcoma by RECIST 1.1 and estimate ORR in a separate cohort of patients with angiosarcoma by RECIST 1.1. Up to 89 patients will be treated in phase 2, including two cohorts of up to 13 patients with angiosarcoma.
Detailed description
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. Pazopanib is approved for the treatment of advanced soft tissue sarcoma, following progression on one prior systemic therapy, based on improved progression free survival. TRC105 is an antibody to CD105, an important angiogenic target on vascular endothelial cells that is distinct from VEGFR. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical models and complements the activity of bevacizumab and multi-kinase inhibitors that target the VEGFR. In a phase 1 study of advanced solid tumors, TRC105 therapy caused a global reduction in angiogenic biomarkers and reduced tumor burden at doses that were well-tolerated. In a phase 1b study, the combination of TRC105 and bevacizumab produced radiographic reductions in tumor volume in bevacizumab-refractory patients, and was well tolerated. TRC105 potentiates bevacizumab and VEGFR tyrosine kinases (VEGFR TKI) in preclinical models. By targeting a non-VEGF pathway that is upregulated following VEGF inhibition, TRC105 has the potential to complement VEGFR TKIs and could represent a major advance in cancer therapy. 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TRC105 and Pazopanib | Experimental | Drug: TRC105 and PazopanibWeekly TRC105 in combination with standard dose pazopanib or every two week administration during cycle 1, and starting on cycle 2 day 1 and beyond, TRC105 may be administered every two weeks. This is also in combination with standard dose pazopanib. |
Who may qualify
- Ages
- 12 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Histologically confirmed unresectable soft tissue sarcoma that has progressed following treatment with chemotherapy. Prior pazopanib is allowed if the drug was not discontinued for toxicity ( Phase 1b only)
- Histologically confirmed metastatic soft tissue sarcoma that has progressed by RECIST following treatment with anthracycline chemotherapy. Patients may have received up to four lines of systemic therapy for metastatic disease and no more than two lines of combination treatment ( Phase 2 only)
- Histologically confirmed locally advanced (e.g. unresectable) or metastatic angiosarcoma that has progressed following treatment with prior systemic therapy. Progression must be documented on or following the most recent systemic therapy. Prior pazopanib is allowed if the drug was not discontinued for toxicity (Phase 2 angiosarcoma cohorts only)
- Measurable disease by RECIST
- Age of 12 years or older (patient must weigh ≥ 40 kg)
Key exclusion criteria (20 listed)
- Prior treatment with TRC105
- Prior treatment with a VEGFR TKI (including pazopanib) (Phase 2 only)
- Current treatment on another therapeutic clinical trial
- Receipt of systemic anticancer therapy, including investigational agents, within 28 days of starting study treatment.
- No major surgical procedure or significant traumatic injury within 6 weeks prior to study registration, and must have fully recovered from any such procedure; date of surgery (if applicable) or the anticipated need for a major surgical procedure within the next six months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TRC105 and PazopanibAlso: Chimeric Antibody (TRC105) to CD105, VotrientWeekly TRC105 in combination with standard dose Pazopanib. | Drug | TRC105 and Pazopanib |
Primary outcome
Number of Participants With Dose Limiting Toxicity (DLT)
Time frame: 56 days
For DLT evaluation, severity (grade) was classified according to common terminology criteria for adverse events version 4.0 (CTCAE v4.0). DLTs were defined as grade 4 neutropenia persisting for ≥ 5 days, febrile neutropenia (grade 4 neutropenia with fever > 38.5 ºC both sustained over a 24 hour period), neutropenic infection (grade ≥ 3 neutropenia with grade ≥ 3 infection), anemia ≥ grade 4, grade > 4 thrombocytopenia or grade ≥ 3 thrombocytopenia and grade ≥ 3 hemorrhage, or grade 3 or 4 nonhematologic toxicity with the following exceptions: nausea, vomiting, or diarrhea for <48 hours, asymptomatic electrolyte abnormalities that are corrected to grade 1 or better in < 72 hours, or headache lasting less than 48 hours.
Progression Free Survival of Patients With Advanced Soft Tissue Sarcoma (Phase 1 and 2)
Time frame: from screening to either disease progression or death
Number of patients with progression free survival, as defined as time from screening to either first disease progression or death from any cause per RECIST version 1.1
Objective Response Rate in a Cohort of Patients With Angiosarcoma
Time frame: 1.5 years
The best response according to RECIST 1.1 for each patient in the phase 2 angiosarcoma cohort with measurable disease and who received at least one dose of study drug will be listed by cohort and tumor type
5 secondary outcomes
Trough Concentrations of TRC105 (Phase 2)
Time frame: 4, 6, 8, and 10 weeks
Number of Patients With and Without Development of Immunogenicity Antibodies (Phase 1 and 2)
Time frame: 32 months
Number of Patients With and Without Expression of Endoglin on Sarcoma Tissue (Phase 1 and 2)
Time frame: 12 months
Objective Response Rate in Patients With Advanced Soft Tissue Sarcoma by RECIST 1.1
Time frame: 12 months
Progression Free Survival in a Cohort of Patients With Angiosarcoma (Phase 2)
Time frame: 26 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charles Theuer, MD study director
Tracon Pharmaceuticals Inc.
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TRC105 and Pazopanib in people with Advanced Soft Tissue Sarcoma, run by Tracon Pharmaceuticals Inc. at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose Limiting Toxicity (DLT) (time frame: 56 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2020.