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

April 30, 2020 updated by: Institute of Cancer Research, United Kingdom

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

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

261

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Bristol, United Kingdom
        • Bristol Haematology and Oncology Centre
      • Bristol, United Kingdom
        • Southmead Hospital
      • Chelsea, United Kingdom, SW3 6JJ
        • Royal Marsden Hospital
      • Coventry, United Kingdom
        • University Hospitals Coventry and Warwickshire NHS Trust
      • Dartford, United Kingdom
        • Darent Valley Hospital
      • Derby, United Kingdom
        • Royal Derby Hospital
      • Dorset, United Kingdom
        • Royal Bournemouth General Hospital
      • Edinburgh, United Kingdom, EH4 2XU
        • Western General Hospital
      • Exeter, United Kingdom
        • Royal Devon and Exeter Hospital
      • Glasgow, United Kingdom
        • Beatson West of Scotland Cancer Centre
      • Guildford, United Kingdom, GU2 7XX
        • Royal Surrey County Hospital
      • Halifax, United Kingdom
        • Calderdale Royal Infirmary
      • Huddersfield, United Kingdom
        • Huddersfield Royal Infirmary
      • Inverness, United Kingdom, IV2 3UJ
        • Caithness General Hospital
      • Inverness, United Kingdom, IV2 3UJ
        • Raigmore Hospital
      • Leicester, United Kingdom
        • Leicester Royal Infirmary
      • Lincoln, United Kingdom, LN2 5QY
        • Lincoln County Hospital
      • Liverpool, United Kingdom, L7 8XP
        • Royal Liverpool University Hospital
      • London, United Kingdom, SE1 9RT
        • Guy'S Hospital
      • London, United Kingdom
        • Charing Cross Hospital
      • London, United Kingdom
        • Northwick Park Hospital
      • Manchester, United Kingdom, M13 9WL
        • Manchester Royal Infirmary
      • Middlesbrough, United Kingdom
        • James Cook University Hospital
      • Newcastle upon Tyne, United Kingdom
        • Freeman Hospital
      • Norwich, United Kingdom, NR4 7UY
        • Norfolk and Norwich University Hospital
      • Portsmouth, United Kingdom
        • Queen Alexandra Hospital,
      • Rhyl, United Kingdom, LL18 5UJ
        • Glan Clywd Hospital
      • Romford, Essex, United Kingdom
        • Queen's Hospital,
      • Shrewsbury, United Kingdom, SY3 8XQ
        • Royal Shrewsbury Hospital
      • Southampton, United Kingdom
        • Southampton General Hospital
      • Stevenage, United Kingdom, SG1 4AA
        • Lister Hospital
      • Stockton-on-Tees, United Kingdom, TS19 8PE
        • University Hospital of North Tees
      • Surrey, United Kingdom, GU16 7UJ
        • Frimley Park Hospital
      • Sutton, United Kingdom, SM2 5PT
        • The Royal Marsden hospital
      • Taunton, United Kingdom
        • Musgrove Park Hospital
      • Torbay, United Kingdom, TQ2 7AA
        • Torbay District General Hospital
      • Treliske, United Kingdom, TR1 3LJ
        • Royal Cornwall Hospital
      • Worthing, United Kingdom, BN11 2DH
        • Worthing Hospital
      • York, United Kingdom, YO31 8HE
        • York District Hospital
    • England
      • Ashford-Kent, England, United Kingdom, TN24 0LZ
        • William Harvey Hospital
      • Barnstaple, England, United Kingdom, EX31 4JB
        • North Devon District Hospital
      • Basildon, England, United Kingdom, SS16 5NL
        • Basildon University Hospital
      • Canterbury, England, United Kingdom, CT2 3NG
        • Kent and Canterbury Hospital
      • Hampstead, London, England, United Kingdom, NW3 2QG
        • Royal Free Hospital
      • Ipswich, England, United Kingdom, IP4 5PD
        • Ipswich Hospital NHS Trust
      • Leeds, England, United Kingdom, LS9 7TF
        • St. James's University Hospital
      • London, England, United Kingdom, EC1M 6BQ
        • Barts and the London School of Medicine
      • Maidstone, England, United Kingdom, ME16 9QQ
        • Maidstone Hospital
      • Manchester, England, United Kingdom, M20 4BX
        • Christie Hospital Nhs Trust
      • Margate, England, United Kingdom, CT9 4AN
        • Queen Elizabeth the Queen Mother Hospital
      • Merseyside, England, United Kingdom, CH63 4JY
        • Clatterbridge Centre for Oncology NHS Trust
      • Nottingham, England, United Kingdom, NG5 1PB
        • Nottingham City Hospital NHS Trust
      • Peterborough, England, United Kingdom, PE3 6DA
        • Peterborough Hospitals Trust
      • Preston, England, United Kingdom, PR2 9HT
        • Rosemere Cancer Centre at Royal Preston Hospital
      • Sheffield, England, United Kingdom, S1O 2SJ
        • Cancer Research Centre at Weston Park Hospital
      • Surrey, England, United Kingdom, SM2 5PT
        • Royal Marsden Hosital, Sutton
      • Westcliff-On-Sea, England, United Kingdom, SS0 0RY
        • Southend University Hospital NHS Foundation Trust
      • Wolverhampton, England, United Kingdom, WV10 0QP
        • New Cross Hospital
    • Scotland
      • Ayr, Scotland, United Kingdom, KA6 6DX
        • Ayr Hospital
    • Wales
      • Cardiff, Wales, United Kingdom, CF14 2TL
        • Velindre Cancer Center at Velinde Hospital
      • Swansea, Wales, United Kingdom, SA 2 8QA
        • Singleton Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 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
Other: 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.
Experimental: 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.
Drug: Chemotherapy
Other Names:
  • Gemcitabine
  • Cisplatin
  • Carboplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease-free survival (DFS)
Time Frame: 3 years
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Patients followed-up for 5 years
Whether adjuvant platinum-based chemotherapy improves overall survival in this patient group
Patients followed-up for 5 years
Metastasis free survival
Time Frame: Patients are followed up for 5 years
To determine whether adjuvant platinum-based chemotherapy improves metastasis free survival in this patient group.
Patients are followed up for 5 years
Incidence of bladder second primary tumours
Time Frame: Patients are followed up for 5 years
Whether adjuvant platinum-based chemotherapy reduces incidence of second primary urothelial cancers
Patients are followed up for 5 years
Incidence of contralateral primary tumours
Time Frame: Patients are followed up for 5 years
To determine whether adjuvant platinum-based chemotherapy reduces incidence of contralateral primary urothelial cancers.
Patients are followed up for 5 years
Acute and late toxicity
Time Frame: Patients are followed up for 5 years
To assess the toxicity of chemotherapy in this patient group.
Patients are followed up for 5 years
Quality of life (QoL)
Time Frame: Patients' QoL will be assessed over 2 years
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institute of Cancer Research, United Kingdom

Collaborators

Cancer Research UK

Investigators

  • Principal Investigator: Dr Alison Birtle, Lancashire Teaching Hospitals NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2012

Primary Completion (Actual)

November 7, 2018

Study Completion (Anticipated)

May 1, 2022

Study Registration Dates

First Submitted

November 19, 2013

First Submitted That Met QC Criteria

November 19, 2013

First Posted (Estimate)

November 25, 2013

Study Record Updates

Last Update Posted (Actual)

May 4, 2020

Last Update Submitted That Met QC Criteria

April 30, 2020

Last Verified

April 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ICR-CTSU/2011/10031
  • 2011-002577-33 (EudraCT Number)
  • ISRCTN98387754 (Registry Identifier: ISRCTN)
  • CRUK/11/027 (Other Grant/Funding Number: Cancer Research UK (CR UK))
  • 11/NW/0782 (Other Identifier: Main REC)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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