Clinical trial NCT03780010: Study of TRC105 + Paclitaxel/Carboplatin and Bevacizumab in Patients With NSCLC
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non Small Cell Lung Cancer
Lead sponsor: Tracon Pharmaceuticals Inc.
Sponsor class: INDUSTRY
Collaborators: name: University of Alabama at Birmingham
First posted: 2018-12-19
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Treatment-Emergent Adverse Events
timeFrame: from screening until completion of follow-up, on average 6 months
Secondary outcomes:
measure: Overall RECIST 1.1 Response Rate
timeFrame: 6 months
measure: Percent of Patients With Progression-free Survival (PFS) at 6 Months
timeFrame: 6 months
measure: Median Progression Free Survival
timeFrame: months
measure: Pharmacokinetic Profile of TRC105 When Given With Bevacizumab and Paclitaxel/Carboplatin
timeFrame: 3 months
measure: Number of Patients Who Have TRC105 Positive Anti-Product Antibodies
timeFrame: 6 months
Other outcomes:
Locations:
Study officials:
affiliation: TRACON Pharmaceuticals
name: Charles Theuer, MD
role: STUDY_DIRECTOR
References: