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Trial of 1 Cycle of Adjuvant BEP Chemotherapy in High Risk, Stage 1 Non-seminomatous Germ Cell Testis Tumours (111)

Primary Purpose

Stage I Testicular Non-Seminomatous Germ Cell Tumor

Status
Unknown status
Phase
Phase 3
Locations
United Kingdom
Study Type
Interventional
Intervention
BEP(500)
Sponsored by
Institute of Cancer Research, United Kingdom
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage I Testicular Non-Seminomatous Germ Cell Tumor

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • Guy's Hospital
  • Northampton General Hospital NHS Trust
  • Velindre Cancer Center at Velindre Hospital
  • Aberdeen Royal Infirmary
  • Ysbyty Gwynedd
  • Queen Elizabeth Hospital
  • Royal Sussex County Hospital
  • Bristol Haematology and Oncology Centre
  • Queen's Hospital
  • Addenbrooke's Hospital
  • Cheltenham General Hospital
  • Gloucestershire Royal Hospital
  • University Hospitals Coventry and Warwickshire NHS Trust
  • Royal Derby Hospital
  • Western General Hospital
  • Royal Devon and Exeter Hospital
  • Beatson West of Scotland Cancer Centre
  • Royal Surrey County Hospital
  • Castle Hill Hospital
  • Ipswich Hospital
  • St James's University Hospital
  • Leicester Royal Infirmary
  • Lincoln County Hospital
  • Clatterbridge Centre for Oncology
  • Royal Liverpool University Hospital
  • St Bartholomew's Hospital
  • University College Hospital
  • Maidstone Hospital
  • James Cook University Hospital
  • Norfolk and Norwich University Hospital
  • Nottingham City Hospital
  • Churchill Hospital
  • Weston Park Hospital
  • Southampton General Hospital
  • Royal Marsden Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

One cycle adjuvant BEP(500)

Arm Description

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

Outcomes

Primary Outcome Measures

Recurrence
To demonstrate that one cycle of adjuvant BEP(500) reduces 2 year recurrence rate to less than 5%

Secondary Outcome Measures

Immediate and delayed toxicity including long-term permanent infertility (>2 years)
Relapse free survival
Overall survival

Full Information

First Posted
November 9, 2012
Last Updated
April 30, 2020
Sponsor
Institute of Cancer Research, United Kingdom
Collaborators
University Hospital Birmingham NHS Foundation Trust, Cancer Research UK
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1. Study Identification

Unique Protocol Identification Number
NCT01726374
Brief Title
Trial of 1 Cycle of Adjuvant BEP Chemotherapy in High Risk, Stage 1 Non-seminomatous Germ Cell Testis Tumours
Acronym
111
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

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Unknown status
Study Start Date
February 2010 (Actual)
Primary Completion Date
August 2016 (Actual)
Study Completion Date
August 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institute of Cancer Research, United Kingdom
Collaborators
University Hospital Birmingham NHS Foundation Trust, Cancer Research UK

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage I Testicular Non-Seminomatous Germ Cell Tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
246 (Actual)

8. Arms, Groups, and Interventions

Arm Title
One cycle adjuvant BEP(500)
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
BEP(500)
Intervention Description
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
Primary Outcome Measure Information:
Title
Recurrence
Description
To demonstrate that one cycle of adjuvant BEP(500) reduces 2 year recurrence rate to less than 5%
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Immediate and delayed toxicity including long-term permanent infertility (>2 years)
Time Frame
0 - > 2 years
Title
Relapse free survival
Time Frame
Patients followed up for 5 years
Title
Overall survival
Time Frame
Patients followed up for 5 years

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Professor Michael Cullen
Organizational Affiliation
University Hospital Birmingham NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Guy's Hospital
City
London
State/Province
England
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
Northampton General Hospital NHS Trust
City
Northampton
State/Province
England
ZIP/Postal Code
NN6 8BJ
Country
United Kingdom
Facility Name
Velindre Cancer Center at Velindre Hospital
City
Cardiff
State/Province
Wales
ZIP/Postal Code
CF14 2TL
Country
United Kingdom
Facility Name
Aberdeen Royal Infirmary
City
Aberdeen
Country
United Kingdom
Facility Name
Ysbyty Gwynedd
City
Bangor
Country
United Kingdom
Facility Name
Queen Elizabeth Hospital
City
Birmingham
Country
United Kingdom
Facility Name
Royal Sussex County Hospital
City
Brighton
Country
United Kingdom
Facility Name
Bristol Haematology and Oncology Centre
City
Bristol
Country
United Kingdom
Facility Name
Queen's Hospital
City
Burton-on-Trent
Country
United Kingdom
Facility Name
Addenbrooke's Hospital
City
Cambridge
Country
United Kingdom
Facility Name
Cheltenham General Hospital
City
Cheltenham
Country
United Kingdom
Facility Name
Gloucestershire Royal Hospital
City
Cheltenham
Country
United Kingdom
Facility Name
University Hospitals Coventry and Warwickshire NHS Trust
City
Coventry
Country
United Kingdom
Facility Name
Royal Derby Hospital
City
Derby
Country
United Kingdom
Facility Name
Western General Hospital
City
Edinburgh
Country
United Kingdom
Facility Name
Royal Devon and Exeter Hospital
City
Exeter
Country
United Kingdom
Facility Name
Beatson West of Scotland Cancer Centre
City
Glasgow
Country
United Kingdom
Facility Name
Royal Surrey County Hospital
City
Guildford
Country
United Kingdom
Facility Name
Castle Hill Hospital
City
Hull
Country
United Kingdom
Facility Name
Ipswich Hospital
City
Ipswich
Country
United Kingdom
Facility Name
St James's University Hospital
City
Leeds
Country
United Kingdom
Facility Name
Leicester Royal Infirmary
City
Leicester
Country
United Kingdom
Facility Name
Lincoln County Hospital
City
Lincoln
Country
United Kingdom
Facility Name
Clatterbridge Centre for Oncology
City
Liverpool
Country
United Kingdom
Facility Name
Royal Liverpool University Hospital
City
Liverpool
Country
United Kingdom
Facility Name
St Bartholomew's Hospital
City
London
Country
United Kingdom
Facility Name
University College Hospital
City
London
Country
United Kingdom
Facility Name
Maidstone Hospital
City
Maidstone
Country
United Kingdom
Facility Name
James Cook University Hospital
City
Middlesbrough
Country
United Kingdom
Facility Name
Norfolk and Norwich University Hospital
City
Norwich
Country
United Kingdom
Facility Name
Nottingham City Hospital
City
Nottingham
Country
United Kingdom
Facility Name
Churchill Hospital
City
Oxford
Country
United Kingdom
Facility Name
Weston Park Hospital
City
Sheffield
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
Country
United Kingdom
Facility Name
Royal Marsden Hospital
City
Sutton
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
31901440
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.
Results Reference
result

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Trial of 1 Cycle of Adjuvant BEP Chemotherapy in High Risk, Stage 1 Non-seminomatous Germ Cell Testis Tumours

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