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

Institute of Cancer Research, United Kingdom

Status and phase: Unknown; Phase 3

Conditions: Transitional Cell Carcinoma of Ureter

Treatments: Other: Surveillance; Drug: Chemotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT01993979

2011-002577-33 (EudraCT Number)

ISRCTN98387754 (Registry Identifier)

11/NW/0782 (Other Identifier)

ICR-CTSU/2011/10031

CRUK/11/027 (Other Grant/Funding Number)

Details and patient eligibility

About

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

Enrollment: 261 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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261 participants in 2 patient groups

Surveillance

Other group

Description:

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

Treatment:

Other: Surveillance

Chemotherapy

Experimental group

Description:

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.

Treatment:

Drug: Chemotherapy