Pharmacodynamic Study of Axitinib in Patients With Advanced Solid Malignancies

Exclusion Criteria

• •Must not havehad chemotherapy, radiotherapy, experimental therapy or major surgery within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered (to grade less than or equal to 1 or baseline) from clinically significant adverse events due to agents administered more than 4 weeks earlier (alopecia and fatigue excluded).
• •* Patients may not be receiving any other investigational agents.
• •* Prior anti-VEGF directed therapy may be allowed only if approved by the PI
• •* Must not have history of allergic reactions attributed to compounds of similar chemical or biologic composition to axitinib.
• •* Must not have poorly controlled hypertension (systolic blood pressure of 140 mmHg or higher or diastolic blood pressure of 90 mmHg or higher)
• •Must not require use of therapeutic doses of coumarin-derivative anticoagulants such as warfarin, although doses of up to 2 mg daily are permitted for prophylaxis of thrombosis.
• •* Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain axitinib tablets are excluded.
• •* Patients with any of the following conditions are excluded:
• •* Serious or non-healing wound, ulcer, or bone fracture.
• •* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment.
• •* Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry.
• •* History of myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry.
• •* History of pulmonary embolism within the past 12 months.
• •* Class III or IV heart failure as defined by the NYHA functional classification system.
• •* Patients without appropriate lesion on CT scan for FLT-PET/CT imaging will be excluded.
• •* The eligibility of patients taking medications that are potent inducers or inhibitors of that enzyme will be determined following a review of their case by the Principal Investigator.
• •* Steroid use is not recommended during axitinib treatment unless absolutely necessary
• •* Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible. Patients with a history of hypothyroidism are eligible provided they are currently euthyroid.
• •* Must not have known brain metastases are excluded.
• •* Must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infections or psychiatric illness/social situations that would limit compliance with study requirements
• •* Must not be pregnant or breastfeeding.
• •* Must not be HIV-positive on combination antiretroviral therapy