Phase I Clinical and Pharmacokinetic Study of Pazopanib in a Population of Frail Elderly Patients According SIOG Criteria

Exclusion Criteria

• •1. Patient with a history of a prior malignancy with the exception of cervical intraepithelial neoplasia; basal cell carcinoma of the skin; adequately treated localized prostate carcinoma with PSA \<1.0; or who has undergone potentially curative therapy with no evidence of that disease for five years, and who is deemed at low risk for recurrence by his/her treating physician,
• •2. History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug.
• •3. Criteria of group 3 according to SIOG classification,
• •4. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
• ••Active peptic ulcer disease
• ••Known intraluminal metastatic lesion/s with risk of bleeding
• ••Inflammatory bowel disease (e.g. ulcerative colitis, crohn's disease), or other gastrointestinal conditions with increased risk of perforation
• ••History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
• •5. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
• ••Malabsorption syndrome
• ••Major resection of the stomach or small bowel.
• •6. Presence of uncontrolled infection.
• •7. Corrected QT interval (QTc) \> 480 msecs using Bazett's formula
• •8. Anti-coagulants treatment (preventive or curative)
• •9. History of any one or more of the following cardiovascular conditions within the past 6 months:
• •• Cardiac angioplasty or stenting
• •• Myocardial infarction
• •• Unstable angina
• •• Coronary artery bypass graft surgery
• •* Symptomatic peripheral vascular disease
• •* Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
• •10. Poorly controlled hypertension
• •11. History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
• •12. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer
• •13. Evidence of active bleeding or bleeding diathesis.
• •14 Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
• •15\. Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks of first dose of study drug.
• •16\. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
• •17\. Unable or unwilling to discontinue use of prohibited medications list in Appendix 7 for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study
• •18\. Treatment with any of the following anti-cancer therapies:
• •radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR
• •chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib
• •19\. Any ongoing toxicity from prior anti-cancer therapy that is \>Grade 1 and/or that is progressing in severity, except alopecia.
• •20\. Patient not affiliated with social system in France.
• •21\. Patient deprived of liberty or under guardianship