A Phase II study of pazopanib in metastatic merkel cell carcinoma
Topic: National Cancer Research Network; Subtopic: Melanoma; Disease: Melanoma
Treatment with Pazopanib, 4 x 200 mg tablets once daily by mouth for 28 days. Treatment will continue until disease progression. Follow Up Length: 60 month(s) Study Entry Details: Registration, followed by trial entry on completion of successful screening
Current inclusion criteria as of 17/01/2014: 1. Patients with histologically proven, unresectable, MCC that is metastatic and/or for which durable control cannot be achieved with surgery or radiotherapy 2. RECIST measurable disease, as per RECIST version 1.1 3. Age ≥18 years, either sex 4. Performance status 0, 1 or 2 assessed using the Eastern Cooperative Oncology Group scale 5. Received previous first line chemotherapy or considered unsuitable for chemotherapy 6. Toxicities from first line chemotherapy resolved to at least grade 1 7. Adequate end organ function 7.1. Renal function tests: serum creatinine ≤150 μmol/L. If serum creatinine is >150 μmol/L, calculated creatinine clearance must be ≥30 ml/min Urine Protein to Creatinine ratio (UPC) <1. If UPC ≥1, then a 24-hour protein must be assessed. Patients must have 24-hour protein value <1 g to be eligible. Alternatively, Albumin/Creatinine ratio may be measured (in accordance with institutional policy, same test to be used for study duration) 7.2. Liver function tests: Total serum bilirubin ≤1.5 X Upper Limit Normal (ULN), Alanine Aminotransferase or Aspartate Aminotransferase (in accordance with institutional policy, same test to be used for study duration) ≤2.5 X ULN (or ≤5 X ULN if liver metastases are present) 7.3. Haematology: Absolute Neutrophil Count (ANC) ≥1.5 X 109/L, Serum creatinine ≤150 μmol/L. If serum creatinine >150 μmol/L, calculated creatinine clearance must be ≥30 ml/min, Urine Protein to Creatinine ratio (UPC) <1. If UPC ≥1, then a 24-hour protein must be assessed. Patients must have 24hour protein value <1 g to be eligible 7.4. Liver function tests: Total serum bilirubin ≤1.5 X Upper Limit Normal (ULN), Alanine Aminotransferase or Aspartate Aminotransferase (in accordance with institutional policy, same test to be used for study duration) ≤2.5 X ULN (or ≤5 X ULN if liver metastases are present) 7.5. Haematology: Absolute Neutrophil Count (ANC) ≥1.5 X 109/L Haemoglobin ≥10 g/dL Platelets
1. Previous malignancies. (Unless agreed in writing by the Chief Investigator or a clinical Coinvestigator, investigators are advised to call the Trial Office). 2. Known brain metastases unless radically treated with surgery or radiotherapy >6 months prior to study entry and without evidence of central nervous system progression since treatment 3. History in the past 6 months of cerebral or clinically significant gastrointestinal haemorrhage 4. Haemoptysis within 6 weeks prior to first dose of study medication 5. Evidence of active bleeding or bleeding diathesis 6. Uncontrolled hypertension defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg. Initiation or adjustment of antihypertensive medication(s) is permitted prior to trial entry 7. Presence of uncontrolled infection 8. History of malabsorption, major gastrointestinal tract resection or other pathology likely to affect absorption of study medication 9. Prolongation of the QT interval (QTc) >480 milliseconds 10. 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 Functional Classification 11. History of cerebrovascular accident including transient ischemic attack within the past 12 months 12. History of pulmonary embolism or untreated deep venous thrombosis within the past 6 months. Patients with a history of thromboembolic disease who are on treatment with therapeutic anticoagulating agents are eligible 13. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels 14. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drug chemically related to pazopanib 15. Major surgery or trauma <4 weeks prior to starting study medication and/or presence of any nonhea