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)

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 Overview

• Status: Completed
• Conditions: Stage I Testicular Non-Seminomatous Germ Cell Tumor
• Intervention / Treatment: Drug: BEP(500)

• Study Type: Interventional
• Enrollment (Actual): 246
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Aberdeen, United Kingdom
    • Aberdeen Royal Infirmary
  • Bangor, United Kingdom
    • Ysbyty Gwynedd
  • Birmingham, United Kingdom
    • Queen Elizabeth Hospital
  • Brighton, United Kingdom
    • Royal Sussex County Hospital
  • Bristol, United Kingdom
    • Bristol Haematology and Oncology centre
  • Burton-on-Trent, United Kingdom
    • Queen's Hospital
  • Cambridge, United Kingdom
    • Addenbrooke's Hospital
  • Cheltenham, United Kingdom
    • Cheltenham General Hospital
  • Cheltenham, United Kingdom
    • Gloucestershire Royal Hospital
  • Coventry, United Kingdom
    • University Hospitals Coventry and Warwickshire NHS Trust
  • Derby, United Kingdom
    • Royal Derby Hospital
  • Edinburgh, United Kingdom
    • Western General Hospital
  • Exeter, United Kingdom
    • Royal Devon and Exeter Hospital
  • Glasgow, United Kingdom
    • Beatson West of Scotland Cancer Centre
  • Guildford, United Kingdom
    • Royal Surrey County Hospital
  • Hull, United Kingdom
    • Castle Hill Hospital
  • Ipswich, United Kingdom
    • Ipswich Hospital
  • Leeds, United Kingdom
    • St James's University Hospital
  • Leicester, United Kingdom
    • Leicester Royal Infirmary
  • Lincoln, United Kingdom
    • Lincoln County Hospital
  • Liverpool, United Kingdom
    • Royal Liverpool University Hospital
  • Liverpool, United Kingdom
    • Clatterbridge Centre for Oncology
  • London, United Kingdom
    • University College Hospital
  • London, United Kingdom
    • St Bartholomew's Hospital
  • Maidstone, United Kingdom
    • Maidstone Hospital
  • Middlesbrough, United Kingdom
    • James Cook University Hospital
  • Norwich, United Kingdom
    • Norfolk and Norwich University Hospital
  • Nottingham, United Kingdom
    • Nottingham City Hospital
  • Oxford, United Kingdom
    • Churchill Hospital
  • Sheffield, United Kingdom
    • Weston Park Hospital
  • Southampton, United Kingdom
    • Southampton General Hospital
  • Sutton, United Kingdom
    • Royal Marsden Hospital
  • England
    • London, England, United Kingdom, SE1 9RT
      • Guy's Hospital
    • Northampton, England, United Kingdom, NN6 8BJ
      • Northampton General Hospital NHS Trust
  • Wales
    • Cardiff, Wales, United Kingdom, CF14 2TL
      • Velindre Cancer Center at Velindre Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: One cycle adjuvant 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: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence	To demonstrate that one cycle of adjuvant BEP(500) reduces 2 year recurrence rate to less than 5%	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Institute of Cancer Research, United Kingdom
• Collaborators: Cancer Research UK; University Hospital Birmingham NHS Foundation Trust
• Investigators: Principal Investigator: Professor Michael Cullen, University Hospital Birmingham NHS Foundation Trust

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2010
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): September 1, 2024

Study Registration Dates

• First Submitted: November 9, 2012
• First Submitted That Met QC Criteria: November 9, 2012
• First Posted (Estimated): November 14, 2012

Study Record Updates

• Last Update Posted (Actual): December 4, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Male Urogenital Diseases; Neoplasms by Histologic Type; Endocrine Gland Neoplasms; Gonadal Disorders; Testicular Diseases; Neoplasms, Germ Cell and Embryonal; Testicular Neoplasms
• Other Study ID Numbers: ICR-CTSU/2008/10019; ISRCTN37875250 (Registry Identifier: ISRCTN); 2008-006295-29 (EudraCT Number); 09/H1102/86 (Other Identifier: Main REC); CRUK/09/011 (Other Grant/Funding Number: CRUK)