## Protocol Section
### Identification Module
**NCT ID:** NCT01993979

**Acronym:** POUT

**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

#### Organization Study ID Info
**ID:** ICR-CTSU/2011/10031
#### Organization
**Class:** OTHER
**Full Name:** Institute of Cancer Research, United Kingdom
#### Secondary ID Infos
**ID:** 2011-002577-33
**Type:** EUDRACT_NUMBER
**Domain:** ISRCTN
**ID:** ISRCTN98387754
**Type:** REGISTRY
**Domain:** Cancer Research UK (CR UK)
**ID:** CRUK/11/027
**Type:** OTHER_GRANT
**Domain:** Main REC
**ID:** 11/NW/0782
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2022-05

**Type:** ESTIMATED

#### Expanded Access Info
**Last Known Status:** ACTIVE_NOT_RECRUITING
#### Last Update Post Date
**Date:** 2020-05-04

**Type:** ACTUAL

**Last Update Submit Date:** 2020-04-30

**Overall Status:** UNKNOWN

#### Primary Completion Date
**Date:** 2018-11-07

**Type:** ACTUAL

#### Start Date
**Date:** 2012-05

**Status Verified Date:** 2020-04

#### Study First Post Date
**Date:** 2013-11-25
**Type:** ESTIMATED
**Study First Submit Date:** 2013-11-19
**Study First Submit QC Date:** 2013-11-19
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Cancer Research UK

#### Lead Sponsor

**Class:** OTHER

**Name:** Institute of Cancer Research, United Kingdom

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**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

### Conditions Module

**Conditions:**

- Transitional Cell Carcinoma of Ureter

**Keywords:**

- Adjuvant chemotherapy

- Surveillance

- Nephro-ureterectomy

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 261

**Type:** ACTUAL

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**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

**Intervention Names:**

- Other: Surveillance

**Label:** Surveillance

**Type:** OTHER

#### Arm Group 2

**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.

**Intervention Names:**

- Drug: Chemotherapy

**Label:** Chemotherapy

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Chemotherapy

**Name:** Chemotherapy

**Other Names:**

- Gemcitabine

- Cisplatin

- Carboplatin

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Surveillance

**Description:** 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.

**Name:** Surveillance

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Description:** 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.

**Measure:** Disease-free survival (DFS)

**Time Frame:** 3 years

#### Secondary Outcomes

**Description:** Whether adjuvant platinum-based chemotherapy improves overall survival in this patient group

**Measure:** Overall survival

**Time Frame:** Patients followed-up for 5 years

**Description:** To determine whether adjuvant platinum-based chemotherapy improves metastasis free survival in this patient group.

**Measure:** Metastasis free survival

**Time Frame:** Patients are followed up for 5 years

**Description:** Whether adjuvant platinum-based chemotherapy reduces incidence of second primary urothelial cancers

**Measure:** Incidence of bladder second primary tumours

**Time Frame:** Patients are followed up for 5 years

**Description:** To determine whether adjuvant platinum-based chemotherapy reduces incidence of contralateral primary urothelial cancers.

**Measure:** Incidence of contralateral primary tumours

**Time Frame:** Patients are followed up for 5 years

**Description:** To assess the toxicity of chemotherapy in this patient group.

**Measure:** Acute and late toxicity

**Time Frame:** Patients are followed up for 5 years

**Description:** To assess the relative quality of life in patients undergoing adjuvant chemotherapy or surveillance in this patient group.

**Measure:** Quality of life (QoL)

**Time Frame:** Patients' QoL will be assessed over 2 years

### Eligibility Module

**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.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Ashford-Kent

**Country:** United Kingdom

**Facility:** William Harvey Hospital

**State:** England

**Zip:** TN24 0LZ

**Location 2:**

**City:** Barnstaple

**Country:** United Kingdom

**Facility:** North Devon District Hospital

**State:** England

**Zip:** EX31 4JB

**Location 3:**

**City:** Basildon

**Country:** United Kingdom

**Facility:** Basildon University Hospital

**State:** England

**Zip:** SS16 5NL

**Location 4:**

**City:** Canterbury

**Country:** United Kingdom

**Facility:** Kent and Canterbury Hospital

**State:** England

**Zip:** CT2 3NG

**Location 5:**

**City:** Hampstead, London

**Country:** United Kingdom

**Facility:** Royal Free Hospital

**State:** England

**Zip:** NW3 2QG

**Location 6:**

**City:** Ipswich

**Country:** United Kingdom

**Facility:** Ipswich Hospital NHS Trust

**State:** England

**Zip:** IP4 5PD

**Location 7:**

**City:** Leeds

**Country:** United Kingdom

**Facility:** St. James's University Hospital

**State:** England

**Zip:** LS9 7TF

**Location 8:**

**City:** London

**Country:** United Kingdom

**Facility:** Barts and the London School of Medicine

**State:** England

**Zip:** EC1M 6BQ

**Location 9:**

**City:** Maidstone

**Country:** United Kingdom

**Facility:** Maidstone Hospital

**State:** England

**Zip:** ME16 9QQ

**Location 10:**

**City:** Manchester

**Country:** United Kingdom

**Facility:** Christie Hospital NHS Trust

**State:** England

**Zip:** M20 4BX

**Location 11:**

**City:** Margate

**Country:** United Kingdom

**Facility:** Queen Elizabeth The Queen Mother Hospital

**State:** England

**Zip:** CT9 4AN

**Location 12:**

**City:** Merseyside

**Country:** United Kingdom

**Facility:** Clatterbridge Centre for Oncology NHS Trust

**State:** England

**Zip:** CH63 4JY

**Location 13:**

**City:** Nottingham

**Country:** United Kingdom

**Facility:** Nottingham City Hospital NHS Trust

**State:** England

**Zip:** NG5 1PB

**Location 14:**

**City:** Peterborough

**Country:** United Kingdom

**Facility:** Peterborough Hospitals Trust

**State:** England

**Zip:** PE3 6DA

**Location 15:**

**City:** Preston

**Country:** United Kingdom

**Facility:** Rosemere Cancer Centre at Royal Preston Hospital

**State:** England

**Zip:** PR2 9HT

**Location 16:**

**City:** Sheffield

**Country:** United Kingdom

**Facility:** Cancer Research Centre at Weston Park Hospital

**State:** England

**Zip:** S1O 2SJ

**Location 17:**

**City:** Surrey

**Country:** United Kingdom

**Facility:** Royal Marsden Hosital, Sutton

**State:** England

**Zip:** SM2 5PT

**Location 18:**

**City:** Westcliff-On-Sea

**Country:** United Kingdom

**Facility:** Southend University Hospital NHS Foundation Trust

**State:** England

**Zip:** SS0 0RY

**Location 19:**

**City:** Wolverhampton

**Country:** United Kingdom

**Facility:** New Cross Hospital

**State:** England

**Zip:** WV10 0QP

**Location 20:**

**City:** Ayr

**Country:** United Kingdom

**Facility:** Ayr Hospital

**State:** Scotland

**Zip:** KA6 6DX

**Location 21:**

**City:** Cardiff

**Country:** United Kingdom

**Facility:** Velindre Cancer Center at Velinde Hospital

**State:** Wales

**Zip:** CF14 2TL

**Location 22:**

**City:** Swansea

**Country:** United Kingdom

**Facility:** Singleton Hospital

**State:** Wales

**Zip:** SA 2 8QA

**Location 23:**

**City:** Bristol

**Country:** United Kingdom

**Facility:** Bristol Haematology and Oncology Centre

**Location 24:**

**City:** Bristol

**Country:** United Kingdom

**Facility:** Southmead Hospital

**Location 25:**

**City:** Chelsea

**Country:** United Kingdom

**Facility:** Royal Marsden Hospital

**Zip:** SW3 6JJ

**Location 26:**

**City:** Coventry

**Country:** United Kingdom

**Facility:** University Hospitals Coventry and Warwickshire NHS Trust

**Location 27:**

**City:** Dartford

**Country:** United Kingdom

**Facility:** Darent Valley Hospital

**Location 28:**

**City:** Derby

**Country:** United Kingdom

**Facility:** Royal Derby Hospital

**Location 29:**

**City:** Dorset

**Country:** United Kingdom

**Facility:** Royal Bournemouth General Hospital

**Location 30:**

**City:** Edinburgh

**Country:** United Kingdom

**Facility:** Western General Hospital

**Zip:** EH4 2XU

**Location 31:**

**City:** Exeter

**Country:** United Kingdom

**Facility:** Royal Devon and Exeter Hospital

**Location 32:**

**City:** Glasgow

**Country:** United Kingdom

**Facility:** Beatson West of Scotland Cancer Centre

**Location 33:**

**City:** Guildford

**Country:** United Kingdom

**Facility:** Royal Surrey County Hospital

**Zip:** GU2 7XX

**Location 34:**

**City:** Halifax

**Country:** United Kingdom

**Facility:** Calderdale Royal Infirmary

**Location 35:**

**City:** Huddersfield

**Country:** United Kingdom

**Facility:** Huddersfield Royal Infirmary

**Location 36:**

**City:** Inverness

**Country:** United Kingdom

**Facility:** Caithness General Hospital

**Zip:** IV2 3UJ

**Location 37:**

**City:** Inverness

**Country:** United Kingdom

**Facility:** Raigmore Hospital

**Zip:** IV2 3UJ

**Location 38:**

**City:** Leicester

**Country:** United Kingdom

**Facility:** Leicester Royal Infirmary

**Location 39:**

**City:** Lincoln

**Country:** United Kingdom

**Facility:** Lincoln County Hospital

**Zip:** LN2 5QY

**Location 40:**

**City:** Liverpool

**Country:** United Kingdom

**Facility:** Royal Liverpool University Hospital

**Zip:** L7 8XP

**Location 41:**

**City:** London

**Country:** United Kingdom

**Facility:** Guy's Hospital

**Zip:** SE1 9RT

**Location 42:**

**City:** London

**Country:** United Kingdom

**Facility:** Charing Cross Hospital

**Location 43:**

**City:** London

**Country:** United Kingdom

**Facility:** Northwick Park Hospital

**Location 44:**

**City:** Manchester

**Country:** United Kingdom

**Facility:** Manchester Royal Infirmary

**Zip:** M13 9WL

**Location 45:**

**City:** Middlesbrough

**Country:** United Kingdom

**Facility:** James Cook University Hospital

**Location 46:**

**City:** Newcastle upon Tyne

**Country:** United Kingdom

**Facility:** Freeman Hospital

**Location 47:**

**City:** Norwich

**Country:** United Kingdom

**Facility:** Norfolk and Norwich University Hospital

**Zip:** NR4 7UY

**Location 48:**

**City:** Portsmouth

**Country:** United Kingdom

**Facility:** Queen Alexandra Hospital,

**Location 49:**

**City:** Rhyl

**Country:** United Kingdom

**Facility:** Glan Clywd Hospital

**Zip:** LL18 5UJ

**Location 50:**

**City:** Romford, Essex

**Country:** United Kingdom

**Facility:** Queen's Hospital,

**Location 51:**

**City:** Shrewsbury

**Country:** United Kingdom

**Facility:** Royal Shrewsbury Hospital

**Zip:** SY3 8XQ

**Location 52:**

**City:** Southampton

**Country:** United Kingdom

**Facility:** Southampton General Hospital

**Location 53:**

**City:** Stevenage

**Country:** United Kingdom

**Facility:** Lister Hospital

**Zip:** SG1 4AA

**Location 54:**

**City:** Stockton-on-Tees

**Country:** United Kingdom

**Facility:** University Hospital of North Tees

**Zip:** TS19 8PE

**Location 55:**

**City:** Surrey

**Country:** United Kingdom

**Facility:** Frimley Park Hospital

**Zip:** GU16 7UJ

**Location 56:**

**City:** Sutton

**Country:** United Kingdom

**Facility:** The Royal Marsden Hospital

**Zip:** SM2 5PT

**Location 57:**

**City:** Taunton

**Country:** United Kingdom

**Facility:** Musgrove Park Hospital

**Location 58:**

**City:** Torbay

**Country:** United Kingdom

**Facility:** Torbay District General Hospital

**Zip:** TQ2 7AA

**Location 59:**

**City:** Treliske

**Country:** United Kingdom

**Facility:** Royal Cornwall Hospital

**Zip:** TR1 3LJ

**Location 60:**

**City:** Worthing

**Country:** United Kingdom

**Facility:** Worthing Hospital

**Zip:** BN11 2DH

**Location 61:**

**City:** York

**Country:** United Kingdom

**Facility:** York District Hospital

**Zip:** YO31 8HE

#### Overall Officials

**Official 1:**

**Affiliation:** Lancashire Teaching Hospitals NHS Foundation Trust

**Name:** Dr Alison Birtle

**Role:** PRINCIPAL_INVESTIGATOR

### References Module

#### References

**Citation:** 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.

**PMID:** 32145825

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000002277

- Term: Carcinoma

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M5534

- Name: Carcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M5551

- Name: Carcinoma, Transitional Cell

- Relevance: HIGH

- As Found: Transitional Cell Carcinoma

- ID: M12320

- Name: Neoplasms, Glandular and Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: T5693

- Name: Transitional Cell Carcinoma

- Relevance: HIGH

- As Found: Transitional Cell Carcinoma

### Condition Browse Module - Meshes

- ID: D000002295

- Term: Carcinoma, Transitional Cell

### Intervention Browse Module - Ancestors

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000000964

- Term: Antimetabolites, Antineoplastic

- ID: D000000963

- Term: Antimetabolites

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M6182

- Name: Cisplatin

- Relevance: HIGH

- As Found: High

- ID: M2985

- Name: Gemcitabine

- Relevance: HIGH

- As Found: Activity

- ID: M18650

- Name: Carboplatin

- Relevance: HIGH

- As Found: System

- ID: M4281

- Name: Antimetabolites

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000002945

- Term: Cisplatin

- ID: D000016190

- Term: Carboplatin

- ID: D000093542

- Term: Gemcitabine

### Misc Info Module

- Version Holder: 2024-05-24
