Study of TRC105 Combined With Standard-Dose Bevacizumab for Advanced Solid Tumors for Which Bevacizumab is Indicated

Phase 1

Completed

• Conditions: Adult Solid Tumor
• Interventions: Drug: TRC105 and Bevacizumab

• Registration Number: NCT01332721
• Lead Sponsor: Tracon Pharmaceuticals Inc.

Brief Summary

The purpose of the study is to evaluate safety and tolerability and determine a recommended Phase 2 dose for TRC105 when added to standard dose bevacizumab in patients with advanced solid tumors for which bevacizumab is indicated.

Detailed Description

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, a monoclonal antibody to CD105, is a novel angiogenesis inhibitor that complements bevacizumab in preclinical models. Together, these antibodies may result in more effective angiogenesis inhibition and improved clinical efficacy over that seen with bevacizumab alone. The purpose of the study is to evaluate safety and tolerability and determine a recommended Phase 2 dose for TRC105 when added to standard dose bevacizumab in patients with advanced solid tumors for which bevacizumab is indicated.

Study Timeline

• Study Start: 2011-04
• Study First Submitted: 2011-04-07
• Study First Submitted QC: 2011-04-08
• Study First Posted: 2011-04-11
• Primary Completion: 2012-09
• Study Completion: 2013-12
• Results First Submitted: 2014-02-12
• Results First Submitted QC: 2014-02-12
• Results First Posted: 2014-03-28
• Status Verified: 2018-11
• Last Update Submitted: 2018-11-07
• Last Update Posted: 2018-12-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

1. Histologically proven advanced or metastatic solid cancer
2. Measurable disease, evaluable disease or elevation of a relevant soluble tumor marker (e.g., CEA, PSA, CA125)
3. Age of 18 years or older
4. ECOG performance status of 0 or 1
5. Resolution of all acute AEs resulting from prior cancer therapies to NCI CTCAE Grade ≤ 1 or baseline (except alopecia)
6. Adequate organ function
7. Willing and able to consent for self to participate in study

Exclusion Criteria

1. Prior treatment with TRC105
2. Serious dose-limiting toxicity related to prior bevacizumab
3. Current treatment on another therapeutic clinical trial
4. Receipt of an investigational agent within 28 days of starting study treatment
5. Prior surgery (including open biopsy) within 28 days of starting the study treatment
6. Prior radiation therapy or systemic therapy within 21 days of starting the study treatment
7. Minor surgical procedures such as fine needle aspirations, Mediport placement or core biopsies within 7 days of study treatment
8. Uncontrolled chronic hypertension defined as systolic > 140 or diastolic > 90 despite optimal therapy (initiation or adjustment of BP medication prior to study entry allowed provided that the average of 3 BP readings at a visit prior to enrollment is < 140/90 mm Hg)
9. Symptomatic pericardial or pleural effusions
10. Uncontrolled peritoneal effusions requiring paracentesis more frequently than every 2 weeks
11. History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease (except in the expansion cohort at the MTD where brain metastases or primary brain tumors are eligible)
12. Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, DVT, PTCA or CABG within the past 6 months
13. Active bleeding or pathologic condition that carries a high risk of bleeding
14. Thrombolytic or anticoagulant use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy
15. Cardiac dysrhythmias of NCI CTCAE Grade ≥ 2 within the last 28 days
16. Known active viral or nonviral hepatitis
17. Centrally located non-small cell lung cancer (regardless of histologic sub-type), or non-small cell lung cancer of squamous histology.
18. History of hemorrhage or hemoptysis (>½ teaspoon bright red blood) within 6 months of starting study treatment
19. Open wounds or unhealed fractures within 28 days of starting study treatment
20. 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
21. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
22. Pregnancy or breastfeeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TRC105 and Bevacizumab	TRC105 and Bevacizumab	Escalating doses of i.v. TRC105 will be administered weekly beginning with 3 mg/kg in combination with 15 mg/kg bevacizumab given every 3 weeks. Patients will receive TRC105 treatment on Days 1, 8, and 15 and bevacizumab treatment on Day 1 of each 21-day cycle.

Primary Outcome Measures

Name	Time	Method
Determine Maximum Tolerated Dose of TRC105 in Combination With Bevacizumab	1.5 years	Three patients will be initially enrolled and treated at each dose level. If none of these 3 patients experiences a dose-limiting toxicity (DLT) during the 28-day evaluation period, dose escalation will proceed following review of safety data with appropriate site staff including the principal investigators at all sites. If 1 of 3 patients experiences DLT, the cohort will be expanded to 6 patients. The maximum tolerated dose (MTD) will have been exceeded if ≥ 33% of patients experience DLT in a given cohort. DLT will have occurred when a patient has 1 or more toxicity listed in the table below that is at least possibly related to the combination of bevacizumab and TRC105 during the first 28 days (cycle 1).

Secondary Outcome Measures

Name	Time	Method
Objective Response According to RECIST 1.1	1.5 years	The best response according to RECIST 1.1 for each patient with measurable disease and who received at least one dose of study drug will be listed by cohort and tumor type
Immune Response to TRC105	1.5 years	HAMA and HACA titers will be measured at specified time-points.
TRC105 Pharmacokinetic Concentrations	1.5 years	Plasma TRC105 concentrations will be measured at specified timepoints.

Trial Locations

Locations (4)

UCLA Hematology and Oncology; 🇺🇸 Santa Monica, California, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Indiana University Simon Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

Pinnacle Oncology Hematology; 🇺🇸 Scottsdale, Arizona, United States