A Phase III Randomised Trial of Peri-Operative Chemotherapy Versus sUrveillance in Upper Tract Urothelial Cancer (POUT)

NCT ID: NCT01993979

Last Updated: 2020-05-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

261 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-05-31

Study Completion Date

2022-05-31

Brief Summary

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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

Detailed Description

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Conditions

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Transitional Cell Carcinoma of Ureter

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Surveillance

Patients 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

Group Type OTHER

Surveillance

Intervention Type OTHER

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.

Chemotherapy

Patients 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.

Group Type EXPERIMENTAL

Chemotherapy

Intervention Type DRUG

Interventions

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Chemotherapy

Intervention Type DRUG

Surveillance

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.

Intervention Type OTHER

Other Intervention Names

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Gemcitabine Cisplatin Carboplatin

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cancer Research UK

OTHER

Sponsor Role collaborator

Institute of Cancer Research, United Kingdom

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dr Alison Birtle

Role: PRINCIPAL_INVESTIGATOR

Lancashire Teaching Hospitals NHS Foundation Trust

Locations

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William Harvey Hospital

Ashford-Kent, England, United Kingdom

Site Status

North Devon District Hospital

Barnstaple, England, United Kingdom

Site Status

Basildon University Hospital

Basildon, England, United Kingdom

Site Status

Kent and Canterbury Hospital

Canterbury, England, United Kingdom

Site Status

Royal Free Hospital

Hampstead, London, England, United Kingdom

Site Status

Ipswich Hospital NHS Trust

Ipswich, England, United Kingdom

Site Status

St. James's University Hospital

Leeds, England, United Kingdom

Site Status

Barts and the London School of Medicine

London, England, United Kingdom

Site Status

Maidstone Hospital

Maidstone, England, United Kingdom

Site Status

Christie Hospital NHS Trust

Manchester, England, United Kingdom

Site Status

Queen Elizabeth The Queen Mother Hospital

Margate, England, United Kingdom

Site Status

Clatterbridge Centre for Oncology NHS Trust

Merseyside, England, United Kingdom

Site Status

Nottingham City Hospital NHS Trust

Nottingham, England, United Kingdom

Site Status

Peterborough Hospitals Trust

Peterborough, England, United Kingdom

Site Status

Rosemere Cancer Centre at Royal Preston Hospital

Preston, England, United Kingdom

Site Status

Cancer Research Centre at Weston Park Hospital

Sheffield, England, United Kingdom

Site Status

Royal Marsden Hosital, Sutton

Surrey, England, United Kingdom

Site Status

Southend University Hospital NHS Foundation Trust

Westcliff-on-Sea, England, United Kingdom

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New Cross Hospital

Wolverhampton, England, United Kingdom

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Ayr Hospital

Ayr, Scotland, United Kingdom

Site Status

Velindre Cancer Center at Velinde Hospital

Cardiff, Wales, United Kingdom

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Singleton Hospital

Swansea, Wales, United Kingdom

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Bristol Haematology and Oncology Centre

Bristol, , United Kingdom

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Southmead Hospital

Bristol, , United Kingdom

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Royal Marsden Hospital

Chelsea, , United Kingdom

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University Hospitals Coventry and Warwickshire NHS Trust

Coventry, , United Kingdom

Site Status

Darent Valley Hospital

Dartford, , United Kingdom

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Royal Derby Hospital

Derby, , United Kingdom

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Royal Bournemouth General Hospital

Dorset, , United Kingdom

Site Status

Western General Hospital

Edinburgh, , United Kingdom

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Royal Devon and Exeter Hospital

Exeter, , United Kingdom

Site Status

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status

Royal Surrey County Hospital

Guildford, , United Kingdom

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Calderdale Royal Infirmary

Halifax, , United Kingdom

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Huddersfield Royal Infirmary

Huddersfield, , United Kingdom

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Caithness General Hospital

Inverness, , United Kingdom

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Raigmore Hospital

Inverness, , United Kingdom

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Leicester Royal Infirmary

Leicester, , United Kingdom

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Lincoln County Hospital

Lincoln, , United Kingdom

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Royal Liverpool University Hospital

Liverpool, , United Kingdom

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Guy's Hospital

London, , United Kingdom

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Charing Cross Hospital

London, , United Kingdom

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Northwick Park Hospital

London, , United Kingdom

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Manchester Royal Infirmary

Manchester, , United Kingdom

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James Cook University Hospital

Middlesbrough, , United Kingdom

Site Status

Freeman Hospital

Newcastle upon Tyne, , United Kingdom

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Norfolk and Norwich University Hospital

Norwich, , United Kingdom

Site Status

Queen Alexandra Hospital,

Portsmouth, , United Kingdom

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Glan Clywd Hospital

Rhyl, , United Kingdom

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Queen's Hospital,

Romford, Essex, , United Kingdom

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Royal Shrewsbury Hospital

Shrewsbury, , United Kingdom

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Southampton General Hospital

Southampton, , United Kingdom

Site Status

Lister Hospital

Stevenage, , United Kingdom

Site Status

University Hospital of North Tees

Stockton-on-Tees, , United Kingdom

Site Status

Frimley Park Hospital

Surrey, , United Kingdom

Site Status

The Royal Marsden Hospital

Sutton, , United Kingdom

Site Status

Musgrove Park Hospital

Taunton, , United Kingdom

Site Status

Torbay District General Hospital

Torbay, , United Kingdom

Site Status

Royal Cornwall Hospital

Treliske, , United Kingdom

Site Status

Worthing Hospital

Worthing, , United Kingdom

Site Status

York District Hospital

York, , United Kingdom

Site Status

Countries

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United Kingdom

References

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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.

Reference Type RESULT
PMID: 32145825 (View on PubMed)

Birtle 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.

Reference Type DERIVED
PMID: 38350047 (View on PubMed)

Other Identifiers

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2011-002577-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISRCTN98387754

Identifier Type: REGISTRY

Identifier Source: secondary_id

CRUK/11/027

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

11/NW/0782

Identifier Type: OTHER

Identifier Source: secondary_id

ICR-CTSU/2011/10031

Identifier Type: -

Identifier Source: org_study_id

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