Plain English Summary
Study website
Contact information
Type
Scientific
Contact name
Miss Emma Jones
ORCID ID
Contact details
15 Cotswold Road
Sutton
SM2 5NG
United Kingdom
-
POUT-icrctsu@icr.ac.uk
Additional identifiers
EudraCT/CTIS number
2011-002577-33
IRAS number
82914
ClinicalTrials.gov number
NCT01993979
Protocol/serial number
11494, IRAS 82914
Study information
Scientific title
A Phase III randomised trial of PeriOperative chemotherapy versus sUrveillance in upper Tract urothelial cancer
Acronym
POUT
Study hypothesis
POUT is a phase III multicentre randomised controlled trial. The objective is to determine the efficacy, safety and effects on patients quality of life of adjuvant chemotherapy in patients who have undergone radical nephro-ureterectomy for upper urinary tract transitional cell carcinoma (TCC).
Ethics approval(s)
11/NE/0332
Study design
Randomised; Interventional; Design type: Treatment
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Study setting(s)
GP practice
Study type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Topic: National Cancer Research Network; Subtopic: Bladder Cancer, Renal Cancer; Disease: Urothelium
Intervention
Chemotherapy, Gemcitabine 1000mg/m2 day 1 and day 8 as 30 minute intravenous infusion in 500ml sodium chloride; and
Cisplatin 70mg/m2 day 1 as a 4 hour intravenous infusion or (for participants with a creatinine clearance of 25-49ml only) Carboplatin AUC 4.5 or AUC 5 (according to local practice)
Carboplatin will be given to patients who are fit for chemotherapy and fulfil all trial entry criteria but have GFR 30-49 ml/min.
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. Patients on surveillance will then be followed up for signs of recurrence at the same intervals as those who received chemotherapy.; Follow Up Length: 60 month(s)
Intervention type
Drug
Pharmaceutical study type(s)
Phase
Phase III
Drug/device/biological/vaccine name(s)
Gemcitabine, cisplatin, carboplatin
Primary outcome measure
Disease free survival; Timepoint(s): The main time point of interest is three years after randomisation.
Secondary outcome measures
1. Acute toxicity; Timepoint(s): Whilst patients are on treatment and up to 3 months post-randomisation
2. Contralateral second primary utTCC; Timepoint(s): The primary timepoint of interest is 3 years
3. Invasive recurrence/second primary in the bladder; Timepoint(s): The primary timepoint of interest is 3 years after randomisation
4. Late toxicity; Timepoint(s): 6 months, 2 years
5. Metastasis free survival; Timepoint(s): The primary timepoint of interest is 3 years.
6. Overall survival; Timepoint(s): The primary timepoint of interest is 3 years after randomisation
7. Quality of life (QoL) as measured by the EORTC QLQ-C30 and EQ5D modules.; Timepoint(s): We are collecting information on QoL up to 2 years post randomisation
8. Treatment compliance (in the chemotherapy arm); Timepoint(s): Once chemotherapy has been completed; Trial feasibility; Timepoint(s): Defined by recruitment over the first two years
Overall study start date
01/03/2012
Overall study end date
01/03/2017
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Written informed consent
2. >or =18 years of age
3. Post radical nephro-ureterectomy for upper tract tumour with predominant TCC component - squamoid differentiation or mixed TCC/ small cell carcinoma (SCC) is permitted
4. 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)
5. Satisfactory haematological profile (ANC> 1.5 x 109/L, platelet count 100 x 10/L) and liver function tests (bilirubin < 1.5 x ULN, AST and Alkaline phosphatase < 2.5 x ULN), Glomerular filtration rate = 30 mls/min
6. Fit and willing to receive adjuvant chemotherapy with first cycle to be commenced within 90 days of radical nephro-ureterectomy if allocated
7. WHO performance status 0-1.
8. Available for long-term follow-up; Target Gender: Male & Female ; Lower Age Limit 18 no age limit or unit specified
Participant type(s)
Patient
Age group
Adult
Lower age limit
18 Years
Sex
Both
Target number of participants
Planned Sample Size: 345; UK Sample Size: 256
Total final enrolment
261
Participant exclusion criteria
1. Evidence of distant metastases
2. Pure adenocarcinoma, squamous cell carcinoma or small cell or other variant histology
3. Un-resected macroscopic nodal disease
4. Concurrent muscle invasive bladder cancer (patients with concurrent Non-muscle invasive bladder cancer (NMIBC) will be eligible)
5. Glomerular filtration rate (GFR) <30 ml/minute. Gemcitabine-carboplatin can only be given for patients with suboptimal renal function for cisplatin ie 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
6. Significant co-morbid conditions that would interfere with administration of protocol treatment
7. 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)
8. Previous malignancy in the last 5 years except for previous NMIBC, adequately controlled non melanoma skin tumours, carcinoma in situ (CIS) of cervix or Lobular carcinoma in situ (LCIS) of breast or localised prostate cancer in patients who have a life expectancy of over 5 years upon trial entry
Recruitment start date
01/03/2012
Recruitment end date
10/11/2017
Locations
Countries of recruitment
England, United Kingdom
Study participating centre
15 Cotswold Road
Sutton
SM2 5NG
United Kingdom
Sponsor information
Organisation
Institute for Cancer Research (UK)
Sponsor details
Section of Clinical Trials
15 Cotswold Road
Sutton
SM2 5NG
United Kingdom
Sponsor type
Research organisation
Website
ROR
Funders
Funder type
Government
Funder name
Clinical Trials Awards and Advisory Committee (CTAAC) (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Individual participant data (IPD) sharing plan
IPD sharing plan summary
Not provided at time of registration
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Plain English results | No | Yes | |||
| Abstract results | conference abstract | 20/02/2018 | No | No | |
| Results article | results | 18/04/2020 | 10/03/2020 | Yes | No |