Second-line Pazopanib Renal Cell Carcinoma (RCC) Study. CTRIAL-IE (ICORG) 10-01, V5

Exclusion Criteria

• •1. Prior malignancy. Note: Subjects who have had another malignancy and have been disease-free for 3 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
• •2. History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases (surgery plus or minus radiotherapy, radiosurgery, or gamma knife) and meet all 3 of the following criteria are eligible: a) are asymptomatic, b) have had no evidence of active CNS metastases for \> or = 6 months prior to enrolment, and c) have no requirement for steroids or Enzyme -inducing anticonvulsants EIACs.
• •Screening with CNS imaging studies (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) is required only if clinically indicated or if the subject has a history of CNS metastases.
• •3. Clinically significant gastrointestinal abnormalities that may increase the risk for Gastrointestinal (GI) bleeding including, but not limited to:
• •* Active peptic ulcer disease
• •* Known intraluminal metastatic lesion/s with suspected 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.
• •4. 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.
• •5. Presence of uncontrolled infection.
• •6. Prolongation of corrected QT interval (QTc) \> 480 msecs using Bazett's formula
• •7. 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) \[http://www.abouthf.org/questions\_stages.htm, accessed 8th December 2009\]
• •* Class III (Moderate): marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea.
• •* Class IV (Severe): unable to carry out any physical activity without discomfort. Symptoms of cardiac insufficiency at rest. If any physical activity is undertaken, discomfort is increased.
• •8. Poorly controlled hypertension \[defined as systolic blood pressure (SBP) of ≥150 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg\].
• •Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. BP must be re-assessed on two occasions that are separated by a minimum of 1 hour; on each of these occasions, the mean (of 3 readings) SBP / DBP values from each BP assessment must be \<150/90 mmHg in order for a subject to be eligible for the study (see Appendix H for details on BP control and re-assessment prior to study enrollment).
• •Note: A mean BP in 24 hours of \<150/90 mm/Hg is acceptable.
• •9. History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
• •Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible
• •10. 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 (procedures such as catheter placement not considered to be major).
• •11. Evidence of active bleeding or bleeding diathesis.
• •12. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.
• •13. Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks of first dose of study drug.
• •14. 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.
• •15. Unable or unwilling to discontinue use of prohibited medications list in Section 6.2.4 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.
• •16. Treatment with any of the following anti-cancer therapies:
• •* Minor surgical procedure or tumor embolization within 14 days prior to the first dose of pazoapnib
• •* Previous radiotherapy (RT) is permissible provided the measurable disease is outside the RT port. RT must be completed \> 2 weeks prior to registration.
• •* sunitinib, everolimus or temsirolimus within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib Note: No other prior treatment with bevacizumab, sorafenib, immunotherapies, chemotherapy, biologic therapy or investigational therapy is allowed.
• •17. Any ongoing toxicity from prior anti-cancer therapy that is \>Grade 1 and/or that is progressing in severity, except alopecia.
• •18. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib