Clinical trial NCT01726374: Trial of 1 Cycle of Adjuvant BEP Chemotherapy in High Risk, Stage 1 Non-seminomatous Germ Cell Testis Tumours
Official title: A Single Group Trial Evaluating One Cycle of Adjuvant BEP Chemotherapy in High Risk, Stage 1 Non-seminomatous Germ Cell Tumours of the Testis (NSGCTT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Stage I Testicular Non-Seminomatous Germ Cell Tumor
Lead sponsor: Institute of Cancer Research, United Kingdom
Sponsor class: OTHER
Collaborators: name: University Hospital Birmingham NHS Foundation Trust
name: Cancer Research UK
First posted: 2012-11-14
Enrollment: 246
Sex: MALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: High-risk stage 1 NSGCTTs are curable with careful surveillance followed by 3 cycles of BEP (bleomycin, etoposide, cisplatin with 500mg/m2 of etoposide per cycle) chemotherapy for the 40-50% of cases experiencing recurrence. Alternatively, adjuvant chemotherapy with 2 cycles of BEP(at a lower dose than that used for advanced disease - etoposide 360mg/m2) for these patients achieves the same outcome and avoids intensive surveillance, but delivers 33% more chemotherapy cycles on a population basis.

If a single cycle of BEP at the dose used in advanced disease had a similar high rate of relapse-free survival (cure) to that seen with two lower dose cycles, this would reduce the overall burden of chemotherapy and healthcare resource usage and would be likely to lead to a change in practice globally.


Eligibility criteria: Inclusion Criteria:

* Histologically proven non-seminomatous germ cell tumour of combined GCT (NSGCT + seminoma)of the testis
* Histologically proven vascular invasion of the primary tumour into the testicular veins or lymphatics
* Clinical stage 1 patients (normal AFP and HCG, or optimum marker decline approaching normal levels after orchidectomy AND no evidence of metastases on CT of chest, abdomen and pelvis)
* Men aged 16 years or over
* Creatinine clearance \> 50 ml/min
* No previous chemotherapy
* WBC \> 1.5 x 10\^9/l and platelets 100 x 10\^9/l
* Fit to receive chemotherapy
* Able to start BEP(500) chemotherapy as part of 111 study within 6\* weeks of orchidectomy
* Written informed consent \*If there are unavoidable delays this timescale can be extended to 8 weeks

Exclusion Criteria:

* All patients with pure seminoma
* All patients with non-seminoma or combined NSGCT + seminoma \> stage 1
* All patients with no vascular invasion
* Previous chemotherapy
* Patients with second malignancy except contralateral TIN and contralateral germ cell tumour treated by orchidectomy and subsequent surveillance of more than 3 years
* Co-morbidity precluding the safe administration of BEP(500) chemotherapy
* Patients with renal function impairment (bilirubin \>1.25 x ULN and/or AST \>2 x ULN)
* Patients with pre-existing neuropathy
* Patients with pulmonary fibrosis
* Patients with serious illness or medical conditions incompatible with the protocol

Primary outcomes:
measure: Recurrence
timeFrame: 2 years
Secondary outcomes:
measure: Immediate and delayed toxicity including long-term permanent infertility (>2 years)
timeFrame: 0 - > 2 years
measure: Relapse free survival
timeFrame: Patients followed up for 5 years
measure: Overall survival
timeFrame: Patients followed up for 5 years
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Guy's Hospital
state: England
city: Northampton
country: United Kingdom
facility: Northampton General Hospital NHS Trust
state: England
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Bangor
country: United Kingdom
facility: Ysbyty Gwynedd
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Brighton
country: United Kingdom
facility: Royal Sussex County Hospital
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
city: Burton-on-Trent
country: United Kingdom
facility: Queen's Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
city: Cheltenham
country: United Kingdom
facility: Gloucestershire Royal Hospital
city: Coventry
country: United Kingdom
facility: University Hospitals Coventry and Warwickshire NHS Trust
city: Derby
country: United Kingdom
facility: Royal Derby Hospital
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
city: Hull
country: United Kingdom
facility: Castle Hill Hospital
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
city: Leeds
country: United Kingdom
facility: St James's University Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: Lincoln
country: United Kingdom
facility: Lincoln County Hospital
city: Liverpool
country: United Kingdom
facility: Clatterbridge Centre for Oncology
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: London
country: United Kingdom
facility: University College Hospital
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: University Hospital Birmingham NHS Foundation Trust
name: Professor Michael Cullen
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cullen M, Huddart R, Joffe J, Gardiner D, Maynard L, Hutton P, Mazhar D, Shamash J, Wheater M, White J, Goubar A, Porta N, Witts S, Lewis R, Hall E; 111 Trial Management Group. The 111 Study: A Single-arm, Phase 3 Trial Evaluating One Cycle of Bleomycin, Etoposide, and Cisplatin as Adjuvant Chemotherapy in High-risk, Stage 1 Nonseminomatous or Combined Germ Cell Tumours of the Testis. Eur Urol. 2020 Mar;77(3):344-351. doi: 10.1016/j.eururo.2019.11.022. Epub 2020 Jan 1.