GlioblastomaPhase 2105GM201NCT01564914
A Phase 2 Evaluation of TRC105 In Combination With Bevacizumab in Patients With Glioblastoma
A Phase 2 study testing TRC105 and Bevacizumab in people with Glioblastoma and Glioblastoma Multiforme, run by Tracon Pharmaceuticals Inc. at 4 sites in United States.
Trial summary
The purpose of this study is to evaluate the safety and efficacy of TRC105 in patients with recurrent or progressive glioblastoma after prior antiangiogenic therapy (including anti-VEGF therapy) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Glioblastoma Multiforme
- What is being tested?
- TRC105 and Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 4 sitesUnited States
- Study dates
- May 2012to Jun 2015
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with histologically confirmed glioblastoma, recurrent after prior external-beam fractionated radiotherapy and temozolomide chemotherapy.
- Patients with documented radiographic progression following bevacizumab therapy for treatment of glioblastoma.
- Patients with up to 3 prior recurrences are allowed.
- Karnofsky performance status ≥ 70%.
- Age ≥ 18 years old.
- Normal organ function
Who cannot join
- Patients who have had previous treatment with TRC105.
- Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
- Patients with cirrhosis, or active viral or nonviral hepatitis.
- Patients with active bleeding or pathologic conditions that carry a high risk of bleeding,(i.e. hereditary hemorrhagic telangiectasia).
- Patients who are currently receiving anticoagulation treatment
- Patients unwilling or unable to comply with the protocol
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Cincinnati
Cincinnati, Ohio, 45267
University Hospitals of Cleveland
Cleveland, Ohio, 44106
Cleveland Clinic
Cleveland, Ohio, 44195
Ohio State University
Columbus, Ohio, 43210
About this study
Official title: A Phase 2 Evaluation of TRC105 In Combination With Bevacizumab for the Treatment Of Recurrent or Progressive Glioblastoma That Has Progressed on Bevacizumab
The purpose of this study is to evaluate the safety and efficacy of TRC105 in patients with recurrent or progressive glioblastoma after prior antiangiogenic therapy (including anti-VEGF therapy)
Read the detailed description
Angiogenesis plays a central role in the progression of solid cancer. TRC105 is an antibody to CD105, an important non-VEGF angiogenic target on proliferating endothelial cells. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical models. TRC105 has been well tolerated in patients with glioblastoma (GBM) as a single agent. The combination of TRC105 in combination with bevacizumab has demonstrated activity in bevacizumab refractory cancer patients. We hypothesize that TRC105 when administered with bevacizumab will have activity in GBM patients who progress on bevacizumab. By targeting a non-VEGF pathway, TRC105 has the potential to complement VEGF inhibition by bevacizumab, which could represent a major advance in GBM therapy.
- Conditions
- Glioblastoma, Glioblastoma Multiforme
- Being tested
- TRC105, Bevacizumab
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TRC105Drug
Also called carotuximab
10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle
BevacizumabDrug
Also called Avastin
IV
| Study group | Role | What they receive |
|---|---|---|
| TRC105, Bevacizumab | Experimental | Single arm study Receives: Drug: TRC105; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median Overall Survival (OS)
Overall survival assessed by determination from time of informed consent on trial to the date of death of each patient enrolled in the trial
Measured: 6 Months
Secondary outcomes (3)
Median Duration That Patients Remained Progression Free on Study
The median number of months that patients remained progression free was calculated using modified RANO criteria to determine progression. Modified RANO criteria is defined as follows: The largest cross-sectional area on the T1-weighted contrast-enhanced images was selected and measured in 2 dimensions with linear measures on the baseline MRI axial sequence. In addition, the largest cross-sectional area of a contiguous hyperintense lesion on FLAIR sequences was measured on the baseline MRI axial sequence. All subsequent scans were compared against these baseline measures (for both CE and FLAIR). New foci of FLAIR signal abnormality were recorded on each subsequent evaluation. Response was scored.
Measured: Patients are scanned every 8 weeks for approximately 6 months
Number of Participants With Adverse Events
Adverse event frequency per patient according to CTCAE version 4.0.
Measured: Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, an average of 4 months
Number of Patients Who Respond to Study Treatment According to Modified RANO Criteria (Objective Response Rate (ORR)).
Number of patients who respond to study treatment according to modified RANO criteria was calculated (Objective Response Rate (ORR)). Modified RANO criteria is defined as follows: The largest cross-sectional area on the T1-weighted contrast-enhanced images was selected and measured in 2 dimensions with linear measures on the baseline MRI axial sequence. In addition, the largest cross-sectional area of a contiguous hyperintense lesion on FLAIR sequences was measured on the baseline MRI axial sequence. All subsequent scans were compared against these baseline measures (for both CE and FLAIR). New foci of FLAIR signal abnormality were recorded on each subsequent evaluation. Response was scored.
Measured: Patients are scanned every 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2012 (estimated)
- Study startMay 2012
- Primary completionJun 2015
- Study completionJun 2015
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 GlioblastomaStudies 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
- Model description
- A total of 6 initial patients were treated with 10 mg/kg of TRC105 monotherapy. All patients progressed within 2 months of initiating treatment, reflecting the rapid progression. Due to the lack of activity in this disease setting with TRC105 alone, the study was amended to treat patients with 10 mg/kg TRC105 weekly in combination with 10 mg/kg bevacizumab every two weeks.
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tracon Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- The Cleveland Clinic, Case Comprehensive Cancer Center
- Responsible party
- Sponsor
- Investigators
- Charles Theuer, MD PhD, Study director, Tracon Pharmaceuticals Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01564914
- Sponsor's protocol ID
- 105GM201/Case 1312
- Acronym
- 105GM201
- Status last verified
- May 2019
- First submitted
- 26 Mar 2012
- Last updated
- 12 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Evaluation of TRC105 In Combination With Bevacizumab for the Treatment Of Recurrent or Progressive Glioblastoma That Has Progressed on Bevacizumab
- ClinicalTrials.gov ID
- NCT01564914
- Acronym / sponsor ID
- 105GM201 / 105GM201/Case 1312
- Conditions
- Glioblastoma, Glioblastoma Multiforme
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Tracon Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Collaborators
- The Cleveland Clinic, Case Comprehensive Cancer Center
- Study start
- May 2012
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 28 Mar 2012 (estimated)
- Results
- Posted 12 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 this study is to evaluate the safety and efficacy of TRC105 in patients with recurrent or progressive glioblastoma after prior antiangiogenic therapy (including anti-VEGF therapy)
Detailed description
Angiogenesis plays a central role in the progression of solid cancer. TRC105 is an antibody to CD105, an important non-VEGF angiogenic target on proliferating endothelial cells. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical models. TRC105 has been well tolerated in patients with glioblastoma (GBM) as a single agent. The combination of TRC105 in combination with bevacizumab has demonstrated activity in bevacizumab refractory cancer patients. We hypothesize that TRC105 when administered with bevacizumab will have activity in GBM patients who progress on bevacizumab. By targeting a non-VEGF pathway, TRC105 has the potential to complement VEGF inhibition by bevacizumab, which could represent a major advance in GBM therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- A total of 6 initial patients were treated with 10 mg/kg of TRC105 monotherapy. All patients progressed within 2 months of initiating treatment, reflecting the rapid progression. Due to the lack of activity in this disease setting with TRC105 alone, the study was amended to treat patients with 10 mg/kg TRC105 weekly in combination with 10 mg/kg bevacizumab every two weeks.
| Arm | Type | Receives |
|---|---|---|
| TRC105, Bevacizumab | Experimental | Drug: TRC105, Drug: BevacizumabSingle arm study |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients with histologically confirmed glioblastoma, recurrent after prior external-beam fractionated radiotherapy and temozolomide chemotherapy.
- Patients with documented radiographic progression following bevacizumab therapy for treatment of glioblastoma.
- Patients with up to 3 prior recurrences are allowed.
- Karnofsky performance status ≥ 70%.
- Age ≥ 18 years old.
Key exclusion criteria (6 listed)
- Patients who have had previous treatment with TRC105.
- Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
- Patients with cirrhosis, or active viral or nonviral hepatitis.
- Patients with active bleeding or pathologic conditions that carry a high risk of bleeding,(i.e. hereditary hemorrhagic telangiectasia).
- Patients who are currently receiving anticoagulation treatment
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: carotuximab10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle | Drug | TRC105, Bevacizumab |
| BevacizumabAlso: AvastinIV | Drug | TRC105, Bevacizumab |
Primary outcome
Median Overall Survival (OS)
Time frame: 6 Months
Overall survival assessed by determination from time of informed consent on trial to the date of death of each patient enrolled in the trial
3 secondary outcomes
Median Duration That Patients Remained Progression Free on Study
Time frame: Patients are scanned every 8 weeks for approximately 6 months
Number of Participants With Adverse Events
Time frame: Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, an average of 4 months
Number of Patients Who Respond to Study Treatment According to Modified RANO Criteria (Objective Response Rate (ORR)).
Time frame: Patients are scanned every 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2019.
- 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 PhD study director
Tracon Pharmaceuticals Inc.
4 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 Glioblastoma and Glioblastoma Multiforme, run by Tracon Pharmaceuticals Inc. at 4 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 6 inclusion and 6 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 12 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 12 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?
Median Overall Survival (OS) (time frame: 6 Months). 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 12 Jun 2019.