Stage I Testicular Non-Seminomatous Germ Cell TumorPhase 3111NCT01726374
Trial of 1 Cycle of Adjuvant BEP Chemotherapy in High Risk, Stage 1 Non-seminomatous Germ Cell Testis Tumours
A Phase 3 study testing BEP(500) in people with Stage I Testicular Non-Seminomatous Germ Cell Tumor, run by Institute of Cancer Research, United Kingdom at 35 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older, men only
- Conditions the study is for
- Stage I Testicular Non-Seminomatous Germ Cell Tumor
- What is being tested?
- BEP(500)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 246 participants
- Where
- 35 sitesUnited Kingdom
- Study dates
- Feb 2010to Sep 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
35 sites in 1 country.
35 sites in 1 country
United Kingdom35 sites
Aberdeen Royal Infirmary
Aberdeen
Ysbyty Gwynedd
Bangor
Queen Elizabeth Hospital
Birmingham
Royal Sussex County Hospital
Brighton
Bristol Haematology and Oncology Centre
Bristol
Queen's Hospital
Burton-on-Trent
Addenbrooke's Hospital
Cambridge
Velindre Cancer Center at Velindre Hospital
Cardiff, Wales, CF14 2TL
Cheltenham General Hospital
Cheltenham
Gloucestershire Royal Hospital
Cheltenham
University Hospitals Coventry and Warwickshire NHS Trust
Coventry
Royal Derby Hospital
Derby
Western General Hospital
Edinburgh
Royal Devon and Exeter Hospital
Exeter
Beatson West of Scotland Cancer Centre
Glasgow
Royal Surrey County Hospital
Guildford
Castle Hill Hospital
Hull
Ipswich Hospital
Ipswich
St James's University Hospital
Leeds
Leicester Royal Infirmary
Leicester
Lincoln County Hospital
Lincoln
Clatterbridge Centre for Oncology
Liverpool
Royal Liverpool University Hospital
Liverpool
Guy's Hospital
London, England, SE1 9RT
St Bartholomew's Hospital
London
University College Hospital
London
Maidstone Hospital
Maidstone
James Cook University Hospital
Middlesbrough
Northampton General Hospital NHS Trust
Northampton, England, NN6 8BJ
Norfolk and Norwich University Hospital
Norwich
Nottingham City Hospital
Nottingham
Churchill Hospital
Oxford
Weston Park Hospital
Sheffield
Southampton General Hospital
Southampton
Royal Marsden Hospital
Sutton
About this study
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)
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.
- Being tested
- BEP(500)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BEP(500)Drug
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
| Study group | Role | What they receive |
|---|---|---|
| One cycle adjuvant BEP(500) | Experimental | 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 Receives: Drug: BEP(500) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence
To demonstrate that one cycle of adjuvant BEP(500) reduces 2 year recurrence rate to less than 5%
Measured: 2 years
Secondary outcomes (3)
Immediate and delayed toxicity including long-term permanent infertility (>2 years)
Measured: 0 - > 2 years
Relapse free survival
Measured: Patients followed up for 5 years
Overall survival
Measured: Patients followed up for 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2012 (estimated)
- Study startFeb 2010
- Primary completionAug 2016
- Study completionSep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Stage I Testicular Non-Seminomatous Germ Cell TumorStudies of the same condition, open and under way.
- More trials run by Institute of Cancer Research, United KingdomThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 246 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Cancer Research, United Kingdom
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital Birmingham NHS Foundation Trust, Cancer Research UK
- Responsible party
- Sponsor
- Investigators
- Professor Michael Cullen, Principal investigator, University Hospital Birmingham NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01726374
- Sponsor's protocol ID
- ICR-CTSU/2008/10019
- Other IDs
- ISRCTN37875250, 2008-006295-29, 09/H1102/86, CRUK/09/011, 2008
- Acronym
- 111
- Status last verified
- Dec 2024
- First submitted
- 9 Nov 2012
- Last updated
- 4 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 31901440
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01726374
- Acronym / sponsor ID
- 111 / ICR-CTSU/2008/10019
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 246 participants (actual)
- Lead sponsor
- Institute of Cancer Research, United KingdomUniversity, hospital or other
- Collaborators
- University Hospital Birmingham NHS Foundation Trust, Cancer Research UK
- Study start
- Feb 2010 (actual)
- Primary completion
- Aug 2016 (actual)
- Study completion
- Sep 2024 (actual)
- First posted
- 14 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| One cycle adjuvant BEP(500) | Experimental | Drug: 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 |
Who may qualify
- Ages
- 16 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BEP(500)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 | Drug | One cycle adjuvant BEP(500) |
Primary outcome
Recurrence
Time frame: 2 years
To demonstrate that one cycle of adjuvant BEP(500) reduces 2 year recurrence rate to less than 5%
3 secondary outcomes
Immediate and delayed toxicity including long-term permanent infertility (>2 years)
Time frame: 0 - > 2 years
Relapse free survival
Time frame: Patients followed up for 5 years
Overall survival
Time frame: Patients followed up for 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2024.
- Results publication: PubMed 31901440Cullen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Professor Michael Cullen principal investigator
University Hospital Birmingham NHS Foundation Trust
35 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing BEP(500) in people with Stage I Testicular Non-Seminomatous Germ Cell Tumor, run by Institute of Cancer Research, United Kingdom at 35 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrence (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01726374, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2024.