Plain English Summary
Trial website
Contact information
Type
Scientific
Primary contact
Dr Joshua Savage
ORCID ID
http://orcid.org/0000-0003-0599-0245
Contact details
Cancer Research UK Clinical Trials Unit
School of Cancer Studies
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
-
UKMCC-01@trials.bham.ac.uk
Additional identifiers
EudraCT number
2011-003226-27
ClinicalTrials.gov number
Protocol/serial number
13736
Study information
Scientific title
A Phase II study of pazopanib in metastatic merkel cell carcinoma
Acronym
UKMCC-01
Study hypothesis
Merkel cell carcinoma (MCC) is a rare neuroendocrine cancer of the skin with poor prognosis. The annual incidence is thought to be 0.6 per 100,000 of population, with approximately 400 cases per year in the UK. In this study we aim to determine if pazopanib is clinically active, as determined by response rate using the RECIST scoring, in advanced MCC and thus warrants further investigation in a phase III trial. Furthermore, through a translational sub-study, we aim to explore the biological features of MCC and relate these to clinical outcome in order to identify possible clinical biomarkers and therapeutic targets.
More details can be found at: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=13736
Ethics approval
NRES Committee North West - Haydock, 02/11/2012, ref: 12/WM/0182
Study design
Non-randomised; Interventional; Design type: Treatment
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Topic: National Cancer Research Network; Subtopic: Melanoma; Disease: Melanoma
Intervention
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
Intervention type
Drug
Phase
Phase II
Drug names
Pazopanib
Primary outcome measure
Clinical response rate; Timepoint(s): Proportion of patients with complete response or confirmed partial response throughout trial
Secondary outcome measures
1. Disease control rate; Timepoint(s): % of patients that have stable disease, a PR, or a CR for more than 12 weeks
2. Duration of response; Timepoint(s): Time from date of first response (partial/complete) to date of progression or death from any cause
3. Overall survival; Timepoint(s): Time from entry into the trial until death from any cause
4. PFS; Timepoint(s): Time from entry into the trial until disease progression or death from any cause
Overall trial start date
02/11/2012
Overall trial end date
01/08/2019
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
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 ≥100 X 10 to the power of 9/L
7.6. Coagulation test: International Normalized Ratio ≤1.2 X ULN, unless on therapeutic anticoagulation. For patients on therapeutic anticoagulation, INR should be stable and in target range
8. Able to give written informed consent
9. Women of childbearing potential, or men in a relationship with a woman of childbearing age, prepared to adopt adequate contraceptive measures if sexually active
10. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures
Previous inclusion criteria:
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 >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
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 ≥100 X 10 to the power of 9/L
7.6. Coagulation test: International Normalized Ratio ≤1.2 X ULN
8. Able to give written informed consent
9. Women of childbearing potential, or men in a relationship with a woman of childbearing age, prepared to adopt adequate contraceptive measures if sexually active
10. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 25; UK Sample Size: 25
Participant exclusion criteria
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 nonhealing wound, fracture, or ulcer
16. Radiotherapy <2 weeks prior to starting study medication
17. Known HIV, Hepatitis B or C infection
18. 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)
19. 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
20. 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
21. Any serious and/or unstable preexisting medical, psychiatric, or other conditions that could interfere with patients safety, obtaining informed consent or compliance to the study
22. Other contraindications to study medication
Recruitment start date
21/12/2012
Recruitment end date
21/12/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Cancer Research UK Clinical Trials Unit
School of Cancer Studies
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
Sponsor information
Organisation
University of Birmingham (UK)
Sponsor details
Research Support Group
Aston Webb Building
Edgbaston
Birmingham
B15 2TT
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Industry
Funder name
Cancer Research UK (UK) ; Grant Codes: C17955/A12806; CTAAC
Alternative name(s)
CRUK
Funding Body Type
private sector organisation
Funding Body Subtype
Other non-profit organizations
Location
United Kingdom
Funder name
GlaxoSmithKline
Alternative name(s)
GlaxoSmithKline plc., GSK
Funding Body Type
private sector organisation
Funding Body Subtype
For-profit companies (industry)
Location
United Kingdom
Results and Publications
Publication and dissemination plan
We intend to publish protocol, trial results and translational sub-study results.
Intention to publish date
Participant level data
Not expected to be available
Basic results (scientific)
Publication list