Clinical trial NCT01993979: A Phase III Randomised Trial of Peri-Operative Chemotherapy Versus sUrveillance in Upper Tract Urothelial Cancer (POUT)
Official title: A Phase III Randomised Trial of Peri-Operative Chemotherapy Versus sUrveillance in Upper Tract Urothelial Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Transitional Cell Carcinoma of Ureter
Keywords: Adjuvant chemotherapy
Surveillance
Nephro-ureterectomy
Lead sponsor: Institute of Cancer Research, United Kingdom
Sponsor class: OTHER
Collaborators: name: Cancer Research UK
First posted: 2013-11-25
Enrollment: 261
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Disease-free survival (DFS)
timeFrame: 3 years
Secondary outcomes:
measure: Overall survival
timeFrame: Patients followed-up for 5 years
measure: Metastasis free survival
timeFrame: Patients are followed up for 5 years
measure: Incidence of bladder second primary tumours
timeFrame: Patients are followed up for 5 years
measure: Incidence of contralateral primary tumours
timeFrame: Patients are followed up for 5 years
measure: Acute and late toxicity
timeFrame: Patients are followed up for 5 years
measure: Quality of life (QoL)
timeFrame: Patients' QoL will be assessed over 2 years
Other outcomes:
Locations:
city: Ashford-Kent
country: United Kingdom
facility: William Harvey Hospital
state: England
city: Barnstaple
country: United Kingdom
facility: North Devon District Hospital
state: England
city: Basildon
country: United Kingdom
facility: Basildon University Hospital
state: England
city: Canterbury
country: United Kingdom
facility: Kent and Canterbury Hospital
state: England
city: Hampstead, London
country: United Kingdom
facility: Royal Free Hospital
state: England
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital NHS Trust
state: England
city: Leeds
country: United Kingdom
facility: St. James's University Hospital
state: England
city: London
country: United Kingdom
facility: Barts and the London School of Medicine
state: England
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Trust
state: England
city: Margate
country: United Kingdom
facility: Queen Elizabeth The Queen Mother Hospital
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology NHS Trust
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital NHS Trust
state: England
city: Peterborough
country: United Kingdom
facility: Peterborough Hospitals Trust
state: England
city: Preston
country: United Kingdom
facility: Rosemere Cancer Centre at Royal Preston Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Surrey
country: United Kingdom
facility: Royal Marsden Hosital, Sutton
state: England
city: Westcliff-On-Sea
country: United Kingdom
facility: Southend University Hospital NHS Foundation Trust
state: England
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
state: England
city: Ayr
country: United Kingdom
facility: Ayr Hospital
state: Scotland
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velinde Hospital
state: Wales
city: Swansea
country: United Kingdom
facility: Singleton Hospital
state: Wales
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
city: Bristol
country: United Kingdom
facility: Southmead Hospital
city: Chelsea
country: United Kingdom
facility: Royal Marsden Hospital
city: Coventry
country: United Kingdom
facility: University Hospitals Coventry and Warwickshire NHS Trust
city: Dartford
country: United Kingdom
facility: Darent Valley Hospital
city: Derby
country: United Kingdom
facility: Royal Derby Hospital
city: Dorset
country: United Kingdom
facility: Royal Bournemouth General Hospital
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
city: Halifax
country: United Kingdom
facility: Calderdale Royal Infirmary
city: Huddersfield
country: United Kingdom
facility: Huddersfield Royal Infirmary
city: Inverness
country: United Kingdom
facility: Caithness General Hospital
city: Inverness
country: United Kingdom
facility: Raigmore Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: Lincoln
country: United Kingdom
facility: Lincoln County Hospital
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: Charing Cross Hospital
city: London
country: United Kingdom
facility: Northwick Park Hospital
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Freeman Hospital
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
city: Portsmouth
country: United Kingdom
facility: Queen Alexandra Hospital,
city: Rhyl
country: United Kingdom
facility: Glan Clywd Hospital
city: Romford, Essex
country: United Kingdom
facility: Queen's Hospital,
city: Shrewsbury
country: United Kingdom
facility: Royal Shrewsbury Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Stevenage
country: United Kingdom
facility: Lister Hospital
city: Stockton-on-Tees
country: United Kingdom
facility: University Hospital of North Tees
city: Surrey
country: United Kingdom
facility: Frimley Park Hospital
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital
city: Torbay
country: United Kingdom
facility: Torbay District General Hospital
city: Treliske
country: United Kingdom
facility: Royal Cornwall Hospital
city: Worthing
country: United Kingdom
facility: Worthing Hospital
city: York
country: United Kingdom
facility: York District Hospital
Study officials:
affiliation: Lancashire Teaching Hospitals NHS Foundation Trust
name: Dr Alison Birtle
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.