Transitional Cell Carcinoma of Ureter Clinical Trial
— POUTOfficial title:
A Phase III Randomised Trial of Peri-Operative Chemotherapy Versus sUrveillance in Upper Tract Urothelial Cancer
| Verified date | April 2020 |
| Source | Institute of Cancer Research, United Kingdom |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
POUT is a multi-centred randomised controlled phase III trial. 345 patients who have
undergone nephro-ureterectomy, are surgically staged pT2-pT4, N0-3 or are pT1 and node
positive, and who are fit for adjuvant chemotherapy, will be randomised to four cycles of
adjuvant platinum based chemotherapy (experimental group) or surveillance (control group).
Participants will be followed up according to routine practice.
Primary endpoint: Disease-free survival (DFS)
Secondary endpoints:
- Overall Survival
- Metastasis free survival
- Incidence of bladder second primary tumours
- Incidence of contralateral primary tumours
- Acute and late toxicity
- Treatment compliance
- Quality of life
| Status | Active, not recruiting |
| Enrollment | 261 |
| Est. completion date | May 2022 |
| Est. primary completion date | November 7, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - Written informed consent - =18 years of age - Post radical nephro-ureterectomy for upper tract tumour with predominant TCC component - squamoid differentiation or mixed TCC/SCC is permitted. - Histologically confirmed TCC staged pT2-pT4 pN0-3 M0 or pTany N1-3 M0 (providing all grossly abnormal nodes are resected). Patients with microscopically positive margins on pathology may be entered (providing all grossly abnormal disease was resected). - Satisfactory haematological profile (ANC> 1.5 x 109/L, platelet count = 100 x 109/L) and liver function tests (bilirubin < 1.5 x ULN, AST and Alkaline phosphatase < 2.5 x ULN), Glomerular filtration rate =30 mls/min. - Fit and willing to receive adjuvant chemotherapy with first cycle to be commenced within 90 days of radical nephro-ureterectomy if allocated - WHO performance status 0-1. - Available for long-term follow-up Exclusion Criteria: - Evidence of distant metastases - Pure adenocarcinoma, squamous cell carcinoma or small cell or other variant histology - Un-resected macroscopic nodal disease - Concurrent muscle invasive bladder cancer (patients with concurrent Non-muscle invasive bladder cancer (NMIBC) will be eligible) - GFR <30 ml/minute. NB Gemcitabine-carboplatin can only be given for patients with suboptimal renal function for cisplatin i.e. for GFR 30-49ml/min. Patients with poor performance status or co-morbidities that would make them unfit for chemotherapy are ineligible for the trial - Significant co-morbid conditions that would interfere with administration of protocol treatment - Pregnancy; lactating women or women of childbearing potential unwilling or unable to use adequate non-hormonal contraception (male patients should also use contraception if sexually active); - Previous malignancy in the last 5 years except for previous NMIBC, adequately controlled non melanoma skin tumours, CIS of cervix or LCIS of breast or localised prostate cancer in patients who have a life expectancy of over 5 years upon trial entry. |
| Country | Name | City | State |
|---|---|---|---|
| United Kingdom | William Harvey Hospital | Ashford-Kent | England |
| United Kingdom | Ayr Hospital | Ayr | Scotland |
| United Kingdom | North Devon District Hospital | Barnstaple | England |
| United Kingdom | Basildon University Hospital | Basildon | England |
| United Kingdom | Bristol Haematology and Oncology Centre | Bristol | |
| United Kingdom | Southmead Hospital | Bristol | |
| United Kingdom | Kent and Canterbury Hospital | Canterbury | England |
| United Kingdom | Velindre Cancer Center at Velinde Hospital | Cardiff | Wales |
| United Kingdom | Royal Marsden Hospital | Chelsea | |
| United Kingdom | University Hospitals Coventry and Warwickshire NHS Trust | Coventry | |
| United Kingdom | Darent Valley Hospital | Dartford | |
| United Kingdom | Royal Derby Hospital | Derby | |
| United Kingdom | Royal Bournemouth General Hospital | Dorset | |
| United Kingdom | Western General Hospital | Edinburgh | |
| United Kingdom | Royal Devon and Exeter Hospital | Exeter | |
| United Kingdom | Beatson West of Scotland Cancer Centre | Glasgow | |
| United Kingdom | Royal Surrey County Hospital | Guildford | |
| United Kingdom | Calderdale Royal Infirmary | Halifax | |
| United Kingdom | Royal Free Hospital | Hampstead, London | England |
| United Kingdom | Huddersfield Royal Infirmary | Huddersfield | |
| United Kingdom | Caithness General Hospital | Inverness | |
| United Kingdom | Raigmore Hospital | Inverness | |
| United Kingdom | Ipswich Hospital NHS Trust | Ipswich | England |
| United Kingdom | St. James's University Hospital | Leeds | England |
| United Kingdom | Leicester Royal Infirmary | Leicester | |
| United Kingdom | Lincoln County Hospital | Lincoln | |
| United Kingdom | Royal Liverpool University Hospital | Liverpool | |
| United Kingdom | Barts and the London School of Medicine | London | England |
| United Kingdom | Charing Cross Hospital | London | |
| United Kingdom | Guy's Hospital | London | |
| United Kingdom | Northwick Park Hospital | London | |
| United Kingdom | Maidstone Hospital | Maidstone | England |
| United Kingdom | Christie Hospital NHS Trust | Manchester | England |
| United Kingdom | Manchester Royal Infirmary | Manchester | |
| United Kingdom | Queen Elizabeth The Queen Mother Hospital | Margate | England |
| United Kingdom | Clatterbridge Centre for Oncology NHS Trust | Merseyside | England |
| United Kingdom | James Cook University Hospital | Middlesbrough | |
| United Kingdom | Freeman Hospital | Newcastle upon Tyne | |
| United Kingdom | Norfolk and Norwich University Hospital | Norwich | |
| United Kingdom | Nottingham City Hospital NHS Trust | Nottingham | England |
| United Kingdom | Peterborough Hospitals Trust | Peterborough | England |
| United Kingdom | Queen Alexandra Hospital, | Portsmouth | |
| United Kingdom | Rosemere Cancer Centre at Royal Preston Hospital | Preston | England |
| United Kingdom | Glan Clywd Hospital | Rhyl | |
| United Kingdom | Queen's Hospital, | Romford, Essex | |
| United Kingdom | Cancer Research Centre at Weston Park Hospital | Sheffield | England |
| United Kingdom | Royal Shrewsbury Hospital | Shrewsbury | |
| United Kingdom | Southampton General Hospital | Southampton | |
| United Kingdom | Lister Hospital | Stevenage | |
| United Kingdom | University Hospital of North Tees | Stockton-on-Tees | |
| United Kingdom | Frimley Park Hospital | Surrey | |
| United Kingdom | Royal Marsden Hosital, Sutton | Surrey | England |
| United Kingdom | The Royal Marsden Hospital | Sutton | |
| United Kingdom | Singleton Hospital | Swansea | Wales |
| United Kingdom | Musgrove Park Hospital | Taunton | |
| United Kingdom | Torbay District General Hospital | Torbay | |
| United Kingdom | Royal Cornwall Hospital | Treliske | |
| United Kingdom | Southend University Hospital NHS Foundation Trust | Westcliff-On-Sea | England |
| United Kingdom | New Cross Hospital | Wolverhampton | England |
| United Kingdom | Worthing Hospital | Worthing | |
| United Kingdom | York District Hospital | York |
| Lead Sponsor | Collaborator |
|---|---|
| Institute of Cancer Research, United Kingdom | Cancer Research UK |
United Kingdom,
Birtle A, Johnson M, Chester J, Jones R, Dolling D, Bryan RT, Harris C, Winterbottom A, Blacker A, Catto JWF, Chakraborti P, Donovan JL, Elliott PA, French A, Jagdev S, Jenkins B, Keeley FX Jr, Kockelbergh R, Powles T, Wagstaff J, Wilson C, Todd R, Lewis — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Disease-free survival (DFS) | To determine whether adjuvant combination chemotherapy improves the disease-free survival for patients with resected histologically confirmed muscle invasive (pT2-T4, N0-3) or node positive upper tract TCC. | 3 years | |
| Secondary | Overall survival | Whether adjuvant platinum-based chemotherapy improves overall survival in this patient group | Patients followed-up for 5 years | |
| Secondary | Metastasis free survival | To determine whether adjuvant platinum-based chemotherapy improves metastasis free survival in this patient group. | Patients are followed up for 5 years | |
| Secondary | Incidence of bladder second primary tumours | Whether adjuvant platinum-based chemotherapy reduces incidence of second primary urothelial cancers | Patients are followed up for 5 years | |
| Secondary | Incidence of contralateral primary tumours | To determine whether adjuvant platinum-based chemotherapy reduces incidence of contralateral primary urothelial cancers. | Patients are followed up for 5 years | |
| Secondary | Acute and late toxicity | To assess the toxicity of chemotherapy in this patient group. | Patients are followed up for 5 years | |
| Secondary | Quality of life (QoL) | To assess the relative quality of life in patients undergoing adjuvant chemotherapy or surveillance in this patient group. | Patients' QoL will be assessed over 2 years |