Pharmacodynamic Study of Axitinib in Patients With Advanced Solid Malignancies

Inclusion criteria

• Must have histologically or cytologically confirmed solid malignancy (excluding lymphoma) that is metastatic or unresectable and for which no standard therapy exists (although all solid malignancies will be enrolled, a subset will be designated for NSCL cancer will be given due to planned trials in this disease.

• must have measurable disease
• Must be greater than or equal to 18 years old.
• Life expectancy of greater than 12 weeks.
• ECOG performance status less than or equal to 2.
• Patients must have normal organ and marrow function
• Must be willing to undergo planned pharmacodynamic assessments, including serial PET imaging, plasma markers, and pharmacokinetic sampling.
• Women of childbearing potential and men must use adequate form of birth (hormonal or barrier method of birth control
• must have ability to understand and willingness to sign a written informed consent document.

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