Open Label Dose-Finding Study of TRC105 Plus Capecitabine for Metastatic Breast Cancer

• TRC105 pharmacokinetic concentrations [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
  Peak and trough concentrations will be evaluated.
• Immune response to TRC105 [ Time Frame: 1.5 years ] [ Designated as safety issue: Yes ]
  Serial blood samples will be tested for immune response to TRC105.
• Objective response according to RECIST 1.1 [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
  The best response according to RECIST 1.1 for each patient with measurable disease who received at least one dose of study drug will be listed by cohort and tumor type
• Angiogenic biomarker sample analysis [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
  Serial blood samples will be tested for change in angiogenic biomarkers.

The purpose of this study is to determine the recommended phase 2 dose and overall safety and tolerability of TRC105 when given in combination with capecitabine for the treatment of patients with progressive or recurrent metastatic breast cancer.

Inclusion Criteria:

• Histologically proven advanced solid cancer for which curative therapy is not available (Part 1 only)
• Histologically proven metastatic Her-2-negative breast cancer (Part 2 only)
• Measurable disease by RECIST 1.1 criteria (Part 2 only)
• Willing and able to consent for self to participate in study
• Progressive or recurrent disease after prior systemic chemotherapy regimen
• Age ≥ 18 years
• ECOG performance status of 0 or 1
• Resolution of all acute toxic effects of prior therapy to NCI CTCAE Grade ≤ 1 or baseline (except alopecia)
• Adequate organ function

Exclusion Criteria:

• Prior treatment with more than one systemic chemotherapy regimen for metastatic disease.
• Prior treatment with TRC105
• History of hypersensitivity reaction to antimetabolite therapy
• Receipt of an investigational agent within 28 days of starting study treatment
• Prior surgery (including open biopsy), radiation therapy or systemic therapy within 28 days of starting study treatment
• Minor surgical procedures within 14 days prior to first dose of TRC105
• History of brain metastasis, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease
• Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, DVT, PTCA or CABG within the past 6 months
• Uncontrolled chronic hypertension defined as systolic > 140 or diastolic > 90 despite optimal therapy
• Past medical history of acquired or inherited coagulopathy including patients with known hereditary hemorrhagic telangiectasia
• Thrombolytic or anticoagulant use (except to maintain i.v. catheters) within 10 days prior to first dose with TRC105
• Cardiac dysrhythmias of NCI CTCAE Grade ≥ 2 within the last month
• Hemorrhage within 28 days of starting study treatment
• Unhealed wounds within 28 days of starting study treatment
• History of peptic ulcer disease or 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
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
• Known active viral or nonviral hepatitis
• History of hypersensitivity reaction to human or mouse antibody products
• Lung cancer with central chest lesions
• Pregnancy or breastfeeding

• Roswell Park Cancer Institute
• Department of Defense