Clinical trial NCT01332721: Study of TRC105 Combined With Standard-Dose Bevacizumab for Advanced Solid Tumors for Which Bevacizumab is Indicated
Official title: An Open Label Phase 1B Dose-Escalation Study of TRC105 Combined With Standard-Dose Bevacizumab for Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Adult Solid Tumor
Keywords: TRC105
CD105
Endoglin
Solid Tumors
Avastin
Bevacizumab
Lead sponsor: Tracon Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2011-04-11
Enrollment: 38
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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Determine Maximum Tolerated Dose of TRC105 in Combination With Bevacizumab
timeFrame: 1.5 years
Secondary outcomes:
measure: TRC105 Pharmacokinetic Concentrations
timeFrame: 1.5 years
measure: Immune Response to TRC105
timeFrame: 1.5 years
measure: Objective Response According to RECIST 1.1
timeFrame: 1.5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: Pinnacle Oncology Hematology
state: Arizona
city: Santa Monica
country: United States
facility: UCLA Hematology and Oncology
state: California
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
Study officials:
affiliation: Tracon Pharmaceuticals Inc.
name: Charles P Theuer, MD
role: STUDY_DIRECTOR
References: