A Phase III randomised trial of perioperative chemotherapy versus surveillance in upper tract urothelial cancer

ISRCTN	ISRCTN98387754
DOI	https://doi.org/10.1186/ISRCTN98387754
EudraCT/CTIS number	2011-002577-33
IRAS number	82914
ClinicalTrials.gov number	NCT01993979
Secondary identifying numbers	11494, IRAS 82914

Submission date: 31/01/2012
Registration date: 31/01/2012
Last edited: 03/04/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-chemotherapy-after-surgery-cancer-kidney-ureter-pout

Contact information

Miss Emma Jones
Scientific

15 Cotswold Road
Sutton
SM2 5NG
United Kingdom

Email	POUT-icrctsu@icr.ac.uk

Study information

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
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	A Phase III randomised trial of PeriOperative chemotherapy versus sUrveillance in upper Tract urothelial cancer
Study 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
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

Eligibility

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 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 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

Institute for Cancer Research (UK)
Research organisation

Section of Clinical Trials, 15 Cotswold Road
Sutton
SM2 5NG
United Kingdom

Website	http://www.icr.ac.uk/
"ROR"	https://ror.org/043jzw605

Funders

Funder type

Government

Clinical Trials Awards and Advisory Committee (CTAAC) (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

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

Editorial Notes

03/04/2020: Cancer Research UK lay results summary link added to Results (plain English).
11/03/2020: The following changes have been made:
1. The total final enrolment number has been changed from 248 to 261.
2. The IRAS number has been added.
10/03/2020: Publication reference added.
29/08/2019: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
3. ClinicalTrials.gov number added.
22/01/2018: The recruitment end date was changed from 01/03/2017 to 10/11/2017.