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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Stage I Testicular Non-Seminomatous Germ Cell Tumor

Intervention / Treatment
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* Drug: BEP(500)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: One cycle adjuvant BEP(500)<br>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)<br>* 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<br>|

What is the study measuring?
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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 | Measure Description | 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 |