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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Institute of Cancer Research, United Kingdom
Sponsor:
Collaborator:
Cancer Research UK
Information provided by (Responsible Party):
Institute of Cancer Research, United Kingdom
ClinicalTrials.gov Identifier:
NCT01993979
First received: November 19, 2013
Last updated: NA
Last verified: November 2013
History: No changes posted
  Purpose

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

Condition Intervention Phase
Transitional Cell Carcinoma of Ureter
Drug: Chemotherapy
Other: Surveillance
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Randomised Trial of Peri-Operative Chemotherapy Versus sUrveillance in Upper Tract Urothelial Cancer

Resource links provided by NLM:


Further study details as provided by Institute of Cancer Research, United Kingdom:

Primary Outcome Measures:
  • Disease-free survival (DFS) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall survival [ Time Frame: Patients followed-up for 5 years ] [ Designated as safety issue: No ]
    Whether adjuvant platinum-based chemotherapy improves overall survival in this patient group

  • Metastasis free survival [ Time Frame: Patients are followed up for 5 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    To assess the toxicity of chemotherapy in this patient group.

  • Quality of life (QoL) [ Time Frame: Patients' QoL will be assessed over 2 years ] [ Designated as safety issue: No ]
    To assess the relative quality of life in patients undergoing adjuvant chemotherapy or surveillance in this patient group.


Estimated Enrollment: 345
Study Start Date: May 2012
Estimated Study Completion Date: May 2022
Estimated Primary Completion Date: May 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01993979

Contacts
Contact: POUT Trial Manager 0208 722 4288 pout-icrctsu@icr.ac.uk

  Show 61 Study Locations
Sponsors and Collaborators
Institute of Cancer Research, United Kingdom
Cancer Research UK
Investigators
Principal Investigator: Dr Alison Birtle Lancashire Teaching Hospitals NHS Foundation Trust
  More Information

No publications provided

Responsible Party: Institute of Cancer Research, United Kingdom
ClinicalTrials.gov Identifier: NCT01993979     History of Changes
Other Study ID Numbers: ICR-CTSU/2011/10031, 2011-002577-33, ISRCTN98387754, CRUK/11/027, 11/NW/0782
Study First Received: November 19, 2013
Last Updated: November 19, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Institute of Cancer Research, United Kingdom:
Adjuvant chemotherapy
Surveillance
Nephro-ureterectomy

Additional relevant MeSH terms:
Ureteral Neoplasms
Carcinoma, Transitional Cell
Carcinoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Ureteral Diseases
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms

ClinicalTrials.gov processed this record on October 20, 2014