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

Conditions

Transitional Cell Carcinoma of Ureter

Keywords

Adjuvant chemotherapy, Surveillance, Nephro-ureterectomy

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

Alison Birtle, John Chester, Robert J. Jones, Ben Jenkins, Mark Johnson et al. (16 authors)

Journal of Clinical Oncology2021-02-2021 citations

10.1200/jco.2021.39.6_suppl.455

Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial.

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, Kockelbergh R, Powles T, Wagstaff J, Wilson C, Todd R, Lewis R, Hall E.

2020-03-05359 citations

10.1016/s0140-6736(20)30415-3

The role of adjuvant chemotherapy for pT2-4 upper urinary tract urothelial cancer: Exploratory analysis of large multi-institutional study (JCOG1110A).

Junichi Inokuchi, Kentaro Kuroiwa, Hiroyuki Nishiyama, Takahiro Kojima, Yoshiyuki Kakehi et al. (20 authors)

Journal of Clinical Oncology2019-03-01

10.1200/jco.2019.37.7_suppl.374

MP18-03 RESULTS OF POUT - A PHASE III RANDOMISED TRIAL OF PERI-OPERATIVE CHEMOTHERAPY VERSUS SURVEILLANCE IN UPPER TRACT UROTHELIAL CANCER (UTUC)

Alison Birtle, James W.F. Catto, Mark P. Johnson, Roger Kockelbergh, Francis X. Keeley et al. (19 authors)

The Journal of Urology2018-04-011 citations

10.1016/j.juro.2018.02.579

Results of POUT: A phase III randomised trial of perioperative chemotherapy versus surveillance in upper tract urothelial cancer (UTUC).

Alison Birtle, John Chester, Robert Jones Jones, Mark Johnson, Michaela Hill et al. (20 authors)

Journal of Clinical Oncology2018-02-2075 citations

10.1200/jco.2018.36.6_suppl.407

Interventions

DRUGChemotherapy

OTHERSurveillance

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 design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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.

Design outcomes

Primary

Measure	Time frame	Description
Disease-free survival (DFS)	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.

Secondary

Measure	Time frame	Description
Metastasis free survival	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	Patients are followed up for 5 years	Whether adjuvant platinum-based chemotherapy reduces incidence of second primary urothelial cancers
Overall survival	Patients followed-up for 5 years	Whether adjuvant platinum-based chemotherapy improves overall survival in this patient group
Acute and late toxicity	Patients are followed up for 5 years	To assess the toxicity of chemotherapy in this patient group.
Quality of life (QoL)	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.
Incidence of contralateral primary tumours	Patients are followed up for 5 years	To determine whether adjuvant platinum-based chemotherapy reduces incidence of contralateral primary urothelial cancers.

Countries

United Kingdom

Outcome results

None listed