Trial of 1 Cycle of Adjuvant BEP Chemotherapy in High Risk, Stage 1 Non-seminomatous Germ Cell Testis Tumours
111
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)
5 other identifiers
interventional
246
1 country
35
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Feb 2010
Longer than P75 for phase_3
35 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2010
CompletedFirst Submitted
Initial submission to the registry
November 9, 2012
CompletedFirst Posted
Study publicly available on registry
November 14, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2024
CompletedDecember 4, 2024
December 1, 2024
6.5 years
November 9, 2012
December 3, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Recurrence
To demonstrate that one cycle of adjuvant BEP(500) reduces 2 year recurrence rate to less than 5%
2 years
Secondary Outcomes (3)
Immediate and delayed toxicity including long-term permanent infertility (>2 years)
0 - > 2 years
Relapse free survival
Patients followed up for 5 years
Overall survival
Patients followed up for 5 years
Study Arms (1)
One cycle adjuvant BEP(500)
EXPERIMENTALEtoposide 165 mg/m2 IV infusion - days 1, 2, 3 Cisplatin 50 mg/m2 IV infusion - days 1, 2 Bleomycin 30,000 IU IV infusion - days 1 (or 2), 8, 15
Interventions
One cycle of BEP(500): Etoposide 165 mg/m2 IV infusion - days 1, 2, 3 Cisplatin 50 mg/m2 IV infusion - days 1, 2 Bleomycin 30,000 IU IV infusion - days 1 (or 2), 8, 15
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (35)
Guy's Hospital
London, England, SE1 9RT, United Kingdom
Northampton General Hospital NHS Trust
Northampton, England, NN6 8BJ, United Kingdom
Velindre Cancer Center at Velindre Hospital
Cardiff, Wales, CF14 2TL, United Kingdom
Aberdeen Royal Infirmary
Aberdeen, United Kingdom
Ysbyty Gwynedd
Bangor, United Kingdom
Queen Elizabeth Hospital
Birmingham, United Kingdom
Royal Sussex County Hospital
Brighton, United Kingdom
Bristol Haematology and Oncology Centre
Bristol, United Kingdom
Queen's Hospital
Burton-on-Trent, United Kingdom
Addenbrooke's Hospital
Cambridge, United Kingdom
Cheltenham General Hospital
Cheltenham, United Kingdom
Gloucestershire Royal Hospital
Cheltenham, United Kingdom
University Hospitals Coventry and Warwickshire NHS Trust
Coventry, United Kingdom
Royal Derby Hospital
Derby, United Kingdom
Western General Hospital
Edinburgh, United Kingdom
Royal Devon and Exeter Hospital
Exeter, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom
Royal Surrey County Hospital
Guildford, United Kingdom
Castle Hill Hospital
Hull, United Kingdom
Ipswich Hospital
Ipswich, United Kingdom
St James's University Hospital
Leeds, United Kingdom
Leicester Royal Infirmary
Leicester, United Kingdom
Lincoln County Hospital
Lincoln, United Kingdom
Clatterbridge Centre for Oncology
Liverpool, United Kingdom
Royal Liverpool University Hospital
Liverpool, United Kingdom
St Bartholomew's Hospital
London, United Kingdom
University College Hospital
London, United Kingdom
Maidstone Hospital
Maidstone, United Kingdom
James Cook University Hospital
Middlesbrough, United Kingdom
Norfolk and Norwich University Hospital
Norwich, United Kingdom
Nottingham City Hospital
Nottingham, United Kingdom
Churchill Hospital
Oxford, United Kingdom
Weston Park Hospital
Sheffield, United Kingdom
Southampton General Hospital
Southampton, United Kingdom
Royal Marsden Hospital
Sutton, United Kingdom
Related Publications (1)
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.
PMID: 31901440RESULT
Study Officials
- PRINCIPAL INVESTIGATOR
Professor Michael Cullen
University Hospital Birmingham NHS Foundation Trust
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 9, 2012
First Posted
November 14, 2012
Study Start
February 1, 2010
Primary Completion
August 1, 2016
Study Completion
September 1, 2024
Last Updated
December 4, 2024
Record last verified: 2024-12