Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01993979
Recruitment Status : Unknown
Verified April 2020 by Institute of Cancer Research, United Kingdom.
Recruitment status was:  Active, not recruiting
First Posted : November 25, 2013
Last Update Posted : May 4, 2020
Sponsor:
Collaborator:
Cancer Research UK
Information provided by (Responsible Party):
Institute of Cancer Research, United Kingdom

Tracking Information
First Submitted Date  ICMJE November 19, 2013
First Posted Date  ICMJE November 25, 2013
Last Update Posted Date May 4, 2020
Study Start Date  ICMJE May 2012
Actual Primary Completion Date November 7, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 19, 2013)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 19, 2013)
  • Overall survival [ Time Frame: Patients followed-up for 5 years ]
    Whether adjuvant platinum-based chemotherapy improves overall survival in this patient group
  • 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.
  • 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
  • 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.
  • Acute and late toxicity [ Time Frame: Patients are followed up for 5 years ]
    To assess the toxicity of chemotherapy in this patient group.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase III Randomised Trial of Peri-Operative Chemotherapy Versus sUrveillance in Upper Tract Urothelial Cancer (POUT)
Official Title  ICMJE A Phase III Randomised Trial of Peri-Operative Chemotherapy Versus sUrveillance in Upper Tract Urothelial Cancer
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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Transitional Cell Carcinoma of Ureter
Intervention  ICMJE
  • Drug: Chemotherapy
    Other Names:
    • Gemcitabine
    • Cisplatin
    • Carboplatin
  • 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.
Study Arms  ICMJE
  • 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
    Intervention: Other: Surveillance
  • 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.
    Intervention: Drug: Chemotherapy
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Actual Enrollment  ICMJE
 (submitted: April 30, 2020)
261
Original Estimated Enrollment  ICMJE
 (submitted: November 19, 2013)
345
Estimated Study Completion Date  ICMJE May 2022
Actual Primary Completion Date November 7, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01993979
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Institute of Cancer Research, United Kingdom
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Institute of Cancer Research, United Kingdom
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Cancer Research UK
Investigators  ICMJE
Principal Investigator: Dr Alison Birtle Lancashire Teaching Hospitals NHS Foundation Trust
PRS Account Institute of Cancer Research, United Kingdom
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP