Gestational Trophoblastic NeoplasiaPhase 2NCT02664961
Study of TRC105 and Bevacizumab in Patients With Refractory Gestational Trophoblastic Neoplasia (GTN)
A Phase 2 study testing TRC105 and Bevacizumab in people with Gestational Trophoblastic Neoplasia and Choriocarcinoma, run by Tracon Pharmaceuticals Inc. at 3 sites in United States.
Trial summary
The purpose of the study is to determine the overall response rate of single agent TRC105 and the combination of TRC105 and bevacizumab in patients with refractory GTN (including choriocarcinoma, placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT)). Up to 30 patients will be treated. Read more about this study
- Who is it for?
- Ages 16 to 99 years, women only
- Conditions the study is for
- Gestational Trophoblastic Neoplasia, Choriocarcinoma, Placental Site Trophoblastic Tumor
- What is being tested?
- TRC105 and Bevacizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 3 sitesUnited States
- Study dates
- Mar 2016to Nov 2018
- Phase
- Phase 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 16 to 99 years
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Willingness and ability to consent for self to participate in study
- Willingness and ability to comply with study procedures
- Elevated serum hCG (in cases of choriocarcinoma); elevated hCG or measurable disease (in cases of PSTT or ETT)
- Histologically proven trophoblastic neoplasia, or clinically demonstrated trophoblastic neoplasia that has progressed following treatment with at least one chemotherapy regimen that included 2 or more chemotherapy agents.
- Age of 16 years or older
- ECOG performance status ≤ 1
- Resolution of all acute adverse events resulting from prior cancer therapies to NCI CTCAE grade ≤ 1 or baseline
- Adequate organ function
Who cannot join
- Male
- Prior treatment with TRC105
- . Current treatment on another therapeutic clinical trial
- Uncontrolled chronic hypertension defined as systolic > 150 or diastolic > 90 despite optimal therapy
- Significant pericardial effusion, pleural effusion, or ascites
- Active bleeding or pathologic condition that carries a high risk of bleeding
Show all 20Show fewer
- Tumors located in the central chest or other location where bleeding is associated with high morbidity
- Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy
- Angina, MI, 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 the past 6 months. Deep venous thrombosis within 6 months, unless the patient is therapeutically anti-coagulated for at least 2 weeks. In this situation, low molecular weight heparin is preferred
- Known active viral or nonviral hepatitis
- Pregnant or actively breastfeeding without intention to discontinue prior to initiation of study
- Open wounds or unhealed fractures within 28 days of starting study treatment
- History of peptic ulcer disease or erosive gastritis within the past 6 months, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD) within 28 days of starting study 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
- 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
- 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 brain edema for at least 28 days
- Receipt of systemic anticancer therapy, including investigational agents, within 28 days of starting study treatment. If anticancer therapy was given within 28 days of starting study treatment, patients may be included if 5 times the elimination half-life of the drug has passed
- 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 starting study treatment or those patients who have not recovered adequately from side effects of such therapy
- Major surgical procedure or significant traumatic injury within 6 weeks prior to study registration or not fully recovered from any such procedure
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Ohio State University
Columbus, Ohio, 43210
UT Southwestern
Dallas, Texas, 75390
About this study
Official title: A Phase 2A Study of TRC105 (With Option to Add Bevacizumab) in Patients With Refractory Gestational Trophoblastic Neoplasia (GTN)
The purpose of the study is to determine the overall response rate of single agent TRC105 and the combination of TRC105 and bevacizumab in patients with refractory GTN (including choriocarcinoma, placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT)). Up to 30 patients will be treated.
Read the detailed description
TRC105 is a monoclonal antibody that binds to endoglin, an angiogenic target highly expressed on the tumor vessels and tumor cells in gestational trophoblastic neoplasia (GTN). Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) that inhibits angiogenesis and extends survival in patients with a wide variety of solid tumor types. TRC105 has been well tolerated as a single agent and when combined with bevacizumab. These antibodies may be efficacious in refractory GTN, a tumor type that is highly vascular and has been shown to densely express endoglin.
- Conditions
- Gestational Trophoblastic Neoplasia, Choriocarcinoma, Placental Site Trophoblastic Tumor, Epithelioid Trophoblastic Tumor
- Being tested
- TRC105, Bevacizumab
- Keywords
- TRC105, CD105, Endoglin, Angiogenesis inhibitor, GTN, Bevacizumab, Avastin
- Medical subject headings
- Gestational Trophoblastic Disease, Choriocarcinoma, Trophoblastic Tumor, Placental Site
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TRC105Drug
Also called Chimeric Antibody (TRC105) to CD105
Subjects will begin by receiving TRC105 weekly. Subjects who achieve a complete response on single agent TRC105 may transition to every two week dosing.
BevacizumabDrug
Also called Avastin
Bevacizumab will be dosed every two weeks.
| Study group | Role | What they receive |
|---|---|---|
| TRC105 and/or bevacizumab | Experimental | All subjects will begin by receiving single agent TRC105 weekly. In the case of a complete response to single agent TRC105, subjects will continue to receive single agent TRC105 for at least 3 months following complete response. In the case of a partial response (without a complete response) to single agent TRC105, bevacizumab every two weeks will be added. In the absence of a partial or complete response to single agent TRC105, subjects will receive single agent bevacizumab every two weeks. In the absence of a complete response to single agent bevacizumab, or for subjects who have documented disease progression on a prior bevacizumab containing regimen, subjects will receive TRC105 weekly and bevacizumab every two weeks. Receives: Drug: TRC105; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate on TRC105 Alone and on the Combination of TRC105 and Bevacizumab
Antitumor Activity of Single Agent TRC105 and the Combination of TRC105 and Bevacizumab will be assessed via RECIST 1.1 and by measuring circulating bHCG. Disease progression is defined as >20% increase (the absolute increase must be ≥10 IU/L) above the nadir on consecutive measurements separated by at least two weeks; Partial response is defined as a hCG decrease of 50% or more from starting value on consecutive measurements; Complete response will be defined as normalization of hCG on consecutive measurements separated by at least two weeks; Stable disease will be defined as the absence of response or progression on 3 consecutive measurements separated by at least two weeks.
Measured: 8 weeks
Secondary outcomes (5)
Progression-Free Survival (PFS)
Median Progression-Free Survival (PFS) via Serum hCG levels and response evaluation according to RECIST version 1.1 as a preliminary measure of the antitumor activity of TRC105. Disease progression is defined as >20% increase (the absolute increase must be ≥10 IU/L) above the nadir on consecutive measurements separated by at least two weeks; Partial response is defined as a hCG decrease of 50% or more from starting value on consecutive measurements; Complete response will be defined as normalization of hCG on consecutive measurements separated by at least two weeks; Stable disease will be defined as the absence of response or progression on 3 consecutive measurements separated by at least two weeks. Patients must have screening (baseline) and at least one on study CT scan to be considered evaluable.
Measured: 8 weeks
Overall Response Rate on Bevacizumab Alone
Overall Response Rate on bevacizumab alone according to RECIST 1.1 in combination with serum hCG levels. Disease progression is defined as >20% increase (the absolute increase must be ≥10 IU/L) above the nadir on consecutive measurements separated by at least two weeks; Partial response is defined as a hCG decrease of 50% or more from starting value on consecutive measurements; Complete response will be defined as normalization of hCG on consecutive measurements separated by at least two weeks; Stable disease will be defined as the absence of response or progression on 3 consecutive measurements separated by at least two weeks.
Measured: 8 weeks
Maximum Plasma Concentration (Cmax) of TRC105.
Mean serum TRC105 concentrations were assessed at cycle 1 and cycle 2 on day 1, 8, 15, and 22 and on day 1 of every subsequent cycle using validated methods in order to determine the Cmax of TRC105
Measured: cycle 2 day 1 (28 days after initiation of dosing)
TRC105 Immunogenicity as Assessed by Anti-Product Antibody (APA).
Anti-Product Antibody (APA) concentrations will be measured using validated ELISA methods at the time points specified in the protocol. APA concentrations will be evaluated in the context of pharmacokinetic parameters and AE profiles. Number of patients with positive APA titers on study will be reported.
Measured: 8 weeks
Frequency and Severity of Adverse Events
Determine frequency and severity of adverse events as assessed by NCI CTCAE (Version 4.03)
Measured: 20 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2016 (estimated)
- Study startMar 2016
- Primary completionApr 2018
- Study completionNov 2018
Why it stopped: Rare tumor type, patients eligible via expanded access.
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 Gestational Trophoblastic NeoplasiaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tracon Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Charles Theuer, MD, PhD, Study director, Tracon Pharmaceuticals Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02664961
- Sponsor's protocol ID
- 105GTN201
- Status last verified
- May 2019
- First submitted
- 20 Jan 2016
- Last updated
- 23 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2A Study of TRC105 (With Option to Add Bevacizumab) in Patients With Refractory Gestational Trophoblastic Neoplasia (GTN)
- ClinicalTrials.gov ID
- NCT02664961
- Acronym / sponsor ID
- 105GTN201
- Conditions
- Gestational Trophoblastic Neoplasia, Choriocarcinoma, Placental Site Trophoblastic Tumor, Epithelioid Trophoblastic Tumor
- Keywords
- TRC105, CD105, Endoglin, Angiogenesis inhibitor, GTN, Bevacizumab, Avastin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Rare tumor type, patients eligible via expanded access.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Tracon Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- Mar 2016 (actual)
- Primary completion
- Apr 2018 (actual)
- Study completion
- Nov 2018 (actual)
- First posted
- 27 Jan 2016 (estimated)
- Results
- Posted 4 Jun 2019
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 study is to determine the overall response rate of single agent TRC105 and the combination of TRC105 and bevacizumab in patients with refractory GTN (including choriocarcinoma, placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT)). Up to 30 patients will be treated.
Detailed description
TRC105 is a monoclonal antibody that binds to endoglin, an angiogenic target highly expressed on the tumor vessels and tumor cells in gestational trophoblastic neoplasia (GTN). Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) that inhibits angiogenesis and extends survival in patients with a wide variety of solid tumor types. TRC105 has been well tolerated as a single agent and when combined with bevacizumab. These antibodies may be efficacious in refractory GTN, a tumor type that is highly vascular and has been shown to densely express endoglin.
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/or bevacizumab | Experimental | Drug: TRC105, Drug: BevacizumabAll subjects will begin by receiving single agent TRC105 weekly. In the case of a complete response to single agent TRC105, subjects will continue to receive single agent TRC105 for at least 3 months following complete response. In the case of a partial response (without a complete response) to single agent TRC105, bevacizumab every two weeks will be added. In the absence of a partial or complete response to single agent TRC105, subjects will receive single agent bevacizumab every two weeks. In the absence of a complete response to single agent bevacizumab, or for subjects who have documented disease progression on a prior bevacizumab containing regimen, subjects will receive TRC105 weekly and bevacizumab every two weeks. |
Who may qualify
- Ages
- 16 to 99 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Willingness and ability to consent for self to participate in study
- Willingness and ability to comply with study procedures
- Elevated serum hCG (in cases of choriocarcinoma); elevated hCG or measurable disease (in cases of PSTT or ETT)
- Histologically proven trophoblastic neoplasia, or clinically demonstrated trophoblastic neoplasia that has progressed following treatment with at least one chemotherapy regimen that included 2 or more chemotherapy agents.
- Age of 16 years or older
Key exclusion criteria (20 listed)
- Male
- Prior treatment with TRC105
- . Current treatment on another therapeutic clinical trial
- Uncontrolled chronic hypertension defined as systolic > 150 or diastolic > 90 despite optimal therapy
- Significant pericardial effusion, pleural effusion, or ascites
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 |
|---|---|---|
| TRC105Also: Chimeric Antibody (TRC105) to CD105Subjects will begin by receiving TRC105 weekly. Subjects who achieve a complete response on single agent TRC105 may transition to every two week dosing. | Drug | TRC105 and/or bevacizumab |
| BevacizumabAlso: AvastinBevacizumab will be dosed every two weeks. | Drug | TRC105 and/or bevacizumab |
Primary outcome
Overall Response Rate on TRC105 Alone and on the Combination of TRC105 and Bevacizumab
Time frame: 8 weeks
Antitumor Activity of Single Agent TRC105 and the Combination of TRC105 and Bevacizumab will be assessed via RECIST 1.1 and by measuring circulating bHCG. Disease progression is defined as >20% increase (the absolute increase must be ≥10 IU/L) above the nadir on consecutive measurements separated by at least two weeks; Partial response is defined as a hCG decrease of 50% or more from starting value on consecutive measurements; Complete response will be defined as normalization of hCG on consecutive measurements separated by at least two weeks; Stable disease will be defined as the absence of response or progression on 3 consecutive measurements separated by at least two weeks.
5 secondary outcomes
Progression-Free Survival (PFS)
Time frame: 8 weeks
Overall Response Rate on Bevacizumab Alone
Time frame: 8 weeks
Maximum Plasma Concentration (Cmax) of TRC105.
Time frame: cycle 2 day 1 (28 days after initiation of dosing)
TRC105 Immunogenicity as Assessed by Anti-Product Antibody (APA).
Time frame: 8 weeks
Frequency and Severity of Adverse Events
Time frame: 20 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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, PhD study director
Tracon Pharmaceuticals Inc.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TRC105 and Bevacizumab in people with Gestational Trophoblastic Neoplasia and Choriocarcinoma, run by Tracon Pharmaceuticals Inc. at 3 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 8 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: stopped early, as of the sponsor's last update on 23 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 phase mean?
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 4 Jun 2019). 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?
Overall Response Rate on TRC105 Alone and on the Combination of TRC105 and Bevacizumab (time frame: 8 weeks). 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 23 Jul 2019.