A Phase II Study of Pazopanib in Metastatic Merkel Cell Carcinoma (called UKMCC-01)

Conditions: Metastatic Merkel Cell Carcinoma
MedDRA version: 14.1Level: PTClassification code 10029266Term: Neuroendocrine carcinoma of the skinSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2011-003226-27-GB

Lead Sponsor: niversity of Birmingham

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

• Patients with histologically proven, unresectable, MCC that is metastatic and/or for which durable control cannot be achieved with surgery or radiotherapy
• RECIST measurable disease, as per RECIST version 1.1
• Age =18 years
• Performance status 0, 1 or 2 assessed using the Eastern Cooperative Oncology Group scale
• Received previous first line chemotherapy or considered unsuitable for chemotherapy
• Toxicities from first line chemotherapy resolved to at least grade 1
• Adequate end organ function
o Renal function tests:
- 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 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).
o 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)
o Haematology:
- Absolute Neutrophil Count (ANC) =1.5 X 109/L
- Haemoglobin =10 g/dL
- Platelets =100 X 10 to the power of 9/L
o Coagulation test:
- International Normalized Ratio =1.2 X ULN, unless on therapeutic anti-coagulation. For patients on therapeutic anti-coagulation, INR should be stable and in target range.
• Able to give written informed consent
• Women of child-bearing potential, or men in a relationship with a woman of child- bearing age, prepared to adopt adequate contraceptive measures if sexually active
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

• Previous malignancies. (Unless agreed in writing by the Chief Investigator or a clinical Co-investigator, investigators are advised to call the Trial Office).
• 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
• History in the past 6 months of cerebral or clinically significant gastrointestinal haemorrhage
• Haemoptysis within 6 weeks prior to first dose of study medication
• Evidence of active bleeding or bleeding diathesis
• 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
• Presence of uncontrolled infection
• History of malabsorption, major gastrointestinal tract resection or other pathology likely to affect absorption of study medication
• Prolongation of the QT interval (QTc) >480 milliseconds
• 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 by-pass graft surgery
- Symptomatic peripheral vascular disease
- Class III or IV congestive heart failure, as defined by the New York Heart Association Functional Classification
• History of cerebrovascular accident including transient ischemic attack within the past 12 months
• History of pulmonary embolism or untreated deep venous thrombosis within the past 6 months. Patients with a history of thrombo-embolic disease who are on treatment with therapeutic anticoagulating agents are eligible
• Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drug chemically related to pazopanib
• Major surgery or trauma <4 weeks prior to starting study medication and/or presence of any non-healing wound, fracture, or ulcer
• Radiotherapy <2 weeks prior to starting study medication
• Known HIV, Hepatitis B or C infection
• Pregnant (female patients of child bearing potential should have a urine or blood Human Chorionic Gonadotropin test performed to rule out pregnancy prior to trial entry)
• Lactating females. Patients who agree to discontinue nursing 14 days prior to commencing treatment and do not nurse throughout all the treatment period are eligible
• The use of the following medication is prohibited:
- Previous therapy with agents that target the Vascular Endothelial Growth Factor (VEGF) or Platelet-derived Growth Factor (PDGF) pathways
- Chemotherapy, immunotherapy, biologic therapy, investigational therapy, hormone therapy or use of any prohibited medications within 14 days prior to the first dose of study medication
- Use of drugs which are known strong CYP3A4 inhibitors or inducers within 14 days prior to the first dose of study medication
• Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with patient’s safety, obtaining informed consent or compliance to the study
• Other contraindications to study medication