Study of TRC105 Combined With Standard-Dose Bevacizumab for Advanced Solid Tumors for Which Bevacizumab is Indicated
Condition: Adult Solid Tumor
MeSH terms: Neoplasms
Intervention: TRC105 and Bevacizumab
Intervention description: 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.
Intervention MeSH terms: Bevacizumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: TRC105; CD105; Endoglin; Solid Tumors; Avastin; Bevacizumab

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.
    

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