Study of TRC105 + Paclitaxel/Carboplatin and Bevacizumab in Patients With NSCLC

Study Overview
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Brief Summary
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This is a single center, open-label, nonrandomized, phase 1b, dose-finding study of TRC105 in combination with standard dose bevacizumab and paclitaxel/carboplatin in treatment-naive patients with stage IV non-squamous NSCLC.

Detailed Description
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Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) that inhibits angiogenesis and extends survival in non-squamous non-small cell lung cancer (NSCLC) patients when given with carboplatin and paclitaxel. TRC105 is an antibody to endoglin, an essential angiogenic target expressed on proliferating endothelial cells that is distinct from the VEGFR and overexpressed in response to VEGF inhibition. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical models and complements the activity of antibodies and small molecules that target the VEGFR. 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 was also well tolerated with chemotherapy in a trial with capecitabine in breast cancer patients. The use of TRC105 with bevacizumab and paclitaxel/carboplatin may result in more effective angiogenesis inhibition and improved clinical efficacy over that seen with bevacizumab and paclitaxel/carboplatin alone.

Official Title
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A Phase 1b Dose-escalation Study of TRC105 in Combination With Paclitaxel/Carboplatin and Bevacizumab in Patients With Stage 4 Non-Squamous Cell Lung Cancer

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: TRC105


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Stage 4 Non-Squamous Cell Lung Cancer that has not been treated previously with systemic chemotherapy or bevacizumab, but may have received prior targeted treatment (e.g., alk1 inhibitor) ECOG performance status ≤ 1 Measurable disease by RECIST Key Exclusion Criteria: Non-small cell lung cancer of squamous histology Current treatment on another therapeutic clinical trial 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 study registration or those patients who have not recovered adequately from side effects of such therapy Active bleeding or pathologic condition that carries a high risk of bleeding (e.g. hereditary hemorrhagic telangiectasia). Patients who have been uneventfully anti-coagulated with low molecular weight heparin are eligible.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TRC105 + B + P + C<br>TRC105 in combination with standard dose bevacizumab and paclitaxel/carboplatin in treatment-naive patients with stage IV non-squamous NSCLC. | Drug: TRC105<br>* Dose-finding study of TRC105 in combination with standard dose bevacizumab and paclitaxel/carboplatin in treatment-naive patients with stage IV non-squamous NSCLC.<br>* Other names: Carboplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-Emergent Adverse Events | Incidence of treatment-emergent (i.e. TRC105, bevacizumab, paclitaxel and/or carboplatin) adverse events by CTCAE v4.03 | from screening until completion of follow-up, on average 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall RECIST 1.1 Response Rate | Response rate determined according to RECIST 1.1 criteria | 6 months | 
| Percent of Patients With Progression-free Survival (PFS) at 6 Months | Number of patients with progression-free survival at 6 months determined according to RECIST 1.1 criteria | 6 months | 
| Median Progression Free Survival | Median duration of progression free survival according to RECIST 1.1 criteria | months | 
| Pharmacokinetic Profile of TRC105 When Given With Bevacizumab and Paclitaxel/Carboplatin | Trough serum TRC105 pharmacokinetic concentrations at steady state (cycle 3 day 1) will be measured using validated ELISA methods. | 3 months | 
| Number of Patients Who Have TRC105 Positive Anti-Product Antibodies | 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. | 6 months |