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

• ClinicalTrials.gov Identifier: NCT01993979
• Recruitment Status: Unknown
• First Posted: November 25, 2013
• Last Update Posted: May 4, 2020
• Sponsor: Institute of Cancer Research, United Kingdom
• Collaborator: Cancer Research UK
• Information provided by (Responsible Party): Institute of Cancer Research, United Kingdom

Tracking Information

• First Submitted Date: November 19, 2013
• First Posted Date: November 25, 2013
• Last Update Posted Date: May 4, 2020
• Study Start Date: May 2012
• Actual Primary Completion Date: November 7, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase III Randomised Trial of Peri-Operative Chemotherapy Versus sUrveillance in Upper Tract Urothelial Cancer (POUT)
• Official Title: 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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Transitional Cell Carcinoma of Ureter

Intervention

• 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

• 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.

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: April 30, 2020): 261
• Original Estimated Enrollment (submitted: November 19, 2013): 345
• Estimated Study Completion Date: May 2022
• Actual Primary Completion Date: November 7, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT01993979
• 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 )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Institute of Cancer Research, United Kingdom
• Original Responsible Party: Same as current
• Current Study Sponsor: Institute of Cancer Research, United Kingdom
• Original Study Sponsor: Same as current
• Collaborators: Cancer Research UK

Investigators

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

• PRS Account: Institute of Cancer Research, United Kingdom
• Verification Date: April 2020