A Phase III Randomised Trial of Peri-Operative Chemotherapy Versus sUrveillance in Upper Tract Urothelial Cancer (POUT)
POUT
5 other identifiers
interventional
261
1 country
61
Brief Summary
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started May 2012
Longer than P75 for phase_3
61 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2012
CompletedFirst Submitted
Initial submission to the registry
November 19, 2013
CompletedFirst Posted
Study publicly available on registry
November 25, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 7, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2022
CompletedMay 4, 2020
April 1, 2020
6.5 years
November 19, 2013
April 30, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (6)
Overall survival
Patients followed-up for 5 years
Metastasis free survival
Patients are followed up for 5 years
Incidence of bladder second primary tumours
Patients are followed up for 5 years
Incidence of contralateral primary tumours
Patients are followed up for 5 years
Acute and late toxicity
Patients are followed up for 5 years
- +1 more secondary outcomes
Study Arms (2)
Surveillance
OTHERPatients allocated to surveillance will be seen at 4, 7, 10 and 13 weeks post randomisation - equivalent to the end of cycle in patients receiving chemotherapy - in order to collect details of early treatment failure in this group and comparative data relating to toxicity and quality of life. Patients on surveillance will then be followed up for signs of recurrence at the same intervals as those who received chemotherapy
Chemotherapy
EXPERIMENTALPatients allocated adjuvant chemotherapy will receive 4 x 21 day cycles of gemcitabine-cisplatin. Patients who have a sub-optimal renal function (GFR 30-49ml/min) will receive carboplatin instead of cisplatin.
Interventions
Patients will be closely monitored for early signs of recurrence, for which they will receive treatment as decided in discussion between the clinician and patient. This may include chemotherapy.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Institute of Cancer Research, United Kingdomlead
- Cancer Research UKcollaborator
Study Sites (61)
William Harvey Hospital
Ashford-Kent, England, TN24 0LZ, United Kingdom
North Devon District Hospital
Barnstaple, England, EX31 4JB, United Kingdom
Basildon University Hospital
Basildon, England, SS16 5NL, United Kingdom
Kent and Canterbury Hospital
Canterbury, England, CT2 3NG, United Kingdom
Royal Free Hospital
Hampstead, London, England, NW3 2QG, United Kingdom
Ipswich Hospital NHS Trust
Ipswich, England, IP4 5PD, United Kingdom
St. James's University Hospital
Leeds, England, LS9 7TF, United Kingdom
Barts and the London School of Medicine
London, England, EC1M 6BQ, United Kingdom
Maidstone Hospital
Maidstone, England, ME16 9QQ, United Kingdom
Christie Hospital NHS Trust
Manchester, England, M20 4BX, United Kingdom
Queen Elizabeth The Queen Mother Hospital
Margate, England, CT9 4AN, United Kingdom
Clatterbridge Centre for Oncology NHS Trust
Merseyside, England, CH63 4JY, United Kingdom
Nottingham City Hospital NHS Trust
Nottingham, England, NG5 1PB, United Kingdom
Peterborough Hospitals Trust
Peterborough, England, PE3 6DA, United Kingdom
Rosemere Cancer Centre at Royal Preston Hospital
Preston, England, PR2 9HT, United Kingdom
Cancer Research Centre at Weston Park Hospital
Sheffield, England, S1O 2SJ, United Kingdom
Royal Marsden Hosital, Sutton
Surrey, England, SM2 5PT, United Kingdom
Southend University Hospital NHS Foundation Trust
Westcliff-on-Sea, England, SS0 0RY, United Kingdom
New Cross Hospital
Wolverhampton, England, WV10 0QP, United Kingdom
Ayr Hospital
Ayr, Scotland, KA6 6DX, United Kingdom
Velindre Cancer Center at Velinde Hospital
Cardiff, Wales, CF14 2TL, United Kingdom
Singleton Hospital
Swansea, Wales, SA 2 8QA, United Kingdom
Bristol Haematology and Oncology Centre
Bristol, United Kingdom
Southmead Hospital
Bristol, United Kingdom
Royal Marsden Hospital
Chelsea, SW3 6JJ, 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, EH4 2XU, United Kingdom
Royal Devon and Exeter Hospital
Exeter, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom
Royal Surrey County Hospital
Guildford, GU2 7XX, United Kingdom
Calderdale Royal Infirmary
Halifax, United Kingdom
Huddersfield Royal Infirmary
Huddersfield, United Kingdom
Caithness General Hospital
Inverness, IV2 3UJ, United Kingdom
Raigmore Hospital
Inverness, IV2 3UJ, United Kingdom
Leicester Royal Infirmary
Leicester, United Kingdom
Lincoln County Hospital
Lincoln, LN2 5QY, United Kingdom
Royal Liverpool University Hospital
Liverpool, L7 8XP, United Kingdom
Guy's Hospital
London, SE1 9RT, United Kingdom
Charing Cross Hospital
London, United Kingdom
Northwick Park Hospital
London, United Kingdom
Manchester Royal Infirmary
Manchester, M13 9WL, United Kingdom
James Cook University Hospital
Middlesbrough, United Kingdom
Freeman Hospital
Newcastle upon Tyne, United Kingdom
Norfolk and Norwich University Hospital
Norwich, NR4 7UY, United Kingdom
Queen Alexandra Hospital,
Portsmouth, United Kingdom
Glan Clywd Hospital
Rhyl, LL18 5UJ, United Kingdom
Queen's Hospital,
Romford, Essex, United Kingdom
Royal Shrewsbury Hospital
Shrewsbury, SY3 8XQ, United Kingdom
Southampton General Hospital
Southampton, United Kingdom
Lister Hospital
Stevenage, SG1 4AA, United Kingdom
University Hospital of North Tees
Stockton-on-Tees, TS19 8PE, United Kingdom
Frimley Park Hospital
Surrey, GU16 7UJ, United Kingdom
The Royal Marsden Hospital
Sutton, SM2 5PT, United Kingdom
Musgrove Park Hospital
Taunton, United Kingdom
Torbay District General Hospital
Torbay, TQ2 7AA, United Kingdom
Royal Cornwall Hospital
Treliske, TR1 3LJ, United Kingdom
Worthing Hospital
Worthing, BN11 2DH, United Kingdom
York District Hospital
York, YO31 8HE, United Kingdom
Related Publications (2)
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 R, Hall E. Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial. Lancet. 2020 Apr 18;395(10232):1268-1277. doi: 10.1016/S0140-6736(20)30415-3. Epub 2020 Mar 5.
PMID: 32145825RESULTBirtle AJ, Jones R, Chester J, Lewis R, Biscombe K, Johnson M, Blacker A, Bryan RT, Catto JWF, Choudhury A, Das P, Jagdev S, Powles T, Wagstaff J, Cheung KC, Cafferty F, Hall E. Improved Disease-Free Survival With Adjuvant Chemotherapy After Nephroureterectomy for Upper Tract Urothelial Cancer: Final Results of the POUT Trial. J Clin Oncol. 2024 May 1;42(13):1466-1471. doi: 10.1200/JCO.23.01659. Epub 2024 Feb 13.
PMID: 38350047DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Dr Alison Birtle
Lancashire Teaching Hospitals NHS Foundation Trust
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 19, 2013
First Posted
November 25, 2013
Study Start
May 1, 2012
Primary Completion
November 7, 2018
Study Completion
May 1, 2022
Last Updated
May 4, 2020
Record last verified: 2020-04