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Clinical Trial Results:
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)

Summary
EudraCT number	2008-006295-29
Trial protocol	GB
Global end of trial date	11 Sep 2024

Results information
Results version number	v1(current)
This version publication date	23 Oct 2025
First version publication date	23 Oct 2025
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

ICR-CTSU/2008/10019

ISRCTN number

ISRCTN37875250

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

The Institute of Cancer Research (ICR)

Sponsor organisation address

123 Old Brompton Road, London, United Kingdom,

Public contact

111 Trial manager, ICR - Clinical Trials and Statistics Unit, 111-icrctsu@icr.ac.uk

Scientific contact

111 Trial manager, ICR - Clinical Trials and Statistics Unit, 111-icrctsu@icr.ac.uk

Sponsor organisation name

University Hospital Birmingham NHS Trust

Sponsor organisation address

Queen Elizabeth Hospital Birmingham, Mindelsohn Way,Edgbaston, Birmingham, United Kingdom, B15 2GW

Public contact

111 Trial Manager, ICR-Clinical Trials and Statistics Unit, 111-icrctsu@icr.ac.uk

Scientific contact

111 Trial Manager, ICR-Clinical Trials and Statistics Unit, 111-icrctsu@icr.ac.uk

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

11 Sep 2024

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

11 Sep 2024

Was the trial ended prematurely?

Main objective of the trial

To show that one cycle of adjuvant BEP chemotherapy results in a 2 year recurrence rate of less than 5% in patients with high-risk stage 1 NSGCTT

Protection of trial subjects

This trial adhered to the principles outlined in the Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 2004/1031). It was conducted in compliance with the protocol, the Data Protection Act (Z6364106) and other regulatory requirements as appropriate. For trial entry, patients were given a verbal explanation, discussion and written information. The Principal Investigator at each site was responsible for ensuring written informed consent was obtained for each patient. Eligible patients were given as much time as they needed to consider and come to a decision about entering the trial, prior to giving consent for registration. The patient information sheet, described fully which parties would have access to their identifiable personal information and patients were asked to give consent to this. The trial was overseen by an Independent Data Monitoring Committee, who reviewed the accumulating trial data and could recommend stopping the trial if there was any cause for concern about patient safety and if this were the case the patient's oncologist would be notified. BEP(500) chemotherapy was prescribed by the investigator and dispensed from hospital pharmacy from their routine clinical supply for the duration of the trial. For bleomycin, etoposide and cisplatin, drug accountability, destruction and labelling guidelines are contained within the Trial Guidance Notes. All drugs will be labelled ‘for clinical trial use only’. Additional information on the safety and administration of these drugs can be found in their SmPC. For infection prevention, all patients should be given prophylactic GCSF; either pegylated G-CSF 6mg subcut on day 4 or filgrastim daily sc according to local policy. All patients will be given prophylactic antibiotics; either levofloxacin 500mg po (recommended) on days 8 to 15 or ciprofloxacin 500 mg bd on days 8 to 15. TheTrial Steering Committee (TSC) monitored and supervised the progress of the trial.

Background therapy

Testicular cancer is the most common cancer in men aged 20-39. In 2003, 1855 cases were diagnosed in the UK.1 Approximately half of these were in men under 35. Non-seminoma germ cell tumours of the testis (NSGCTT) account for 40-45% of all testicular cancers and combined non-seminoma plus seminoma a further 15%. Approximately 60% of these present with stage 1 disease. Initial treatment for NSGCTT is radical surgery (orchidectomy) usually followed by adjuvant chemotherapy or surveillance. If a single cycle of BEP(500) 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. A practice changing MRC study of two cycles of adjuvant BEP(360) reported an estimated recurrence rate of 2% but only rates >5% could be reliably excluded3. Evidence given below confirms the well known close relationship between long-term toxicity of chemotherapy and the total doses received. Consequently some centres have not adopted adjuvant chemotherapy preferring to offer intensive surveillance and, with a recurrence risk of 45%, thus expose almost half of their cases to at least three cycles of chemotherapy at relapse. During consultation, many such centres in the UK indicated that they would take part in the 111 trial employing just one cycle of chemotherapy if it was powered to exclude a recurrence risk of >5% (as in the original study with two cycles). Evidence summarised above suggests that one cycle is very likely to be as effective as this, and will deliver just half the total doses of chemotherapy and thus less long-term toxicity

Evidence for comparator

111 is a single group trial of a single cycle of adjuvant BEP(500) chemotherapy in high risk stage 1 NSGCTT. It aims to show a two year recurrence rate of less than 5%.

Actual start date of recruitment

18 Mar 2010

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 246

Worldwide total number of subjects

246

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

241

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Between February 18, 2010 and March 31, 2014, 246 patients were registered from 33 UK NHS hospitals

Screening details

Patients newly diagnosed with VI+ stage 1 NSCGCTT able to start chemotherapy (ideally 6wk-8weeks from orchidectomy. Ten patients were replaced after they were identified as ineligible following registration because of raising tumour markers.

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Blinding implementation details

Not applicable

BEP(500)

Arm description

BEP(500) chemotherapy was given as follows: bleomycin 30,000 IU day 1, cisplatin 50 mg/m2 days 1 + 2, etoposide 165 mg/m2 days 1, 2 + 3 followed by bleomycin 30,000 IU days 8 + 15

Arm type

Experimental

Investigational medicinal product name

Bleomycin

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous drip use

Dosage and administration details

Regimen consists of bleomycin 30,000 IU day 1, bleomycin 30,000 IU days 8 + 15. (1) Bleomycin may be given on either days 1 OR 2 depending on local hospital policy. (2) Bleomycin may be given as 30 000IU iv infusion over 30 mins OR alternatively be given as 30 000IU im with 2 mls 1% lignocaine on days 8 and 15. (3) Day 8 and 15 Bleomycin doses may be given +/- 24hours in the case of unavoidable delays e.g. public holidays, low platelets or neutrophils.

Investigational medicinal product name

Etoposide

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous drip use

Dosage and administration details

Etoposide 165 mg/m2 iv infusion Etoposide 165 mg/m2 days 1, 2 + 3

Investigational medicinal product name

Cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for infusion

Routes of administration

Intravenous drip use

Dosage and administration details

Cisplatin 50 mg/m2 iv infusion cisplatin 50 mg/m2 days 1 + 2

Number of subjects in period 1	BEP(500)
Started	246
Eligible and received treatment	236
Completed	236
Not completed	10
Ineligible	10

Baseline characteristics

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Reporting group title

BEP(500)

Reporting group description

BEP(500) chemotherapy was given as follows: bleomycin 30,000 IU day 1, cisplatin 50 mg/m2 days 1 + 2, etoposide 165 mg/m2 days 1, 2 + 3 followed by bleomycin 30,000 IU days 8 + 15

Reporting group values	BEP(500)	Total
Number of subjects	246	246
Age categorical
Units: Subjects
Adolescents (12-17 years)	5	5
Adults (18-64 years)	241	241
From 65-84 years	0	0
Age continuous
Units: years
median (inter-quartile range (Q1-Q3))	30 (25 to 39)	-
Gender categorical
Units: Subjects
Female	0	0
Male	246	246
WHO performance status
Units: Subjects
Zero	230	230
One	9	9
Missing	7	7
Tumour size
Units: Subjects
<2 cm	47	47
2-5 cm	121	121
>5 cm	71	71
Missing	7	7
Stage
Units: Subjects
pT2	237	237
pT3	9	9
Histology type
Units: Subjects
NSGCTT	132	132
Mixed seminoma/NSGCTT	114	114
Lymph nodes status
Units: Subjects
pN0	245	245
pN1+	1	1
Alpha-foetoprotein [AFP] at Baseline
Units: Subjects
Abnormal	16	16
Normal	230	230
Missing	0	0
Alpha-foetoprotein [AFP] at Day 1
Units: Subjects
Normal	2	2
Abnormal	109	109
Missing	135	135
Human chorionic gonadotropin [HCG] at baseline
Units: Subjects
Normal	6	6
Abnormal	240	240
Missing	0	0
Human chorionic gonadotropin [HCG] at Day 1
Units: Subjects
Abnormal	6	6
Normal	108	108
Missing	132	132
Lactate dehydrogenase (LDH) at baseline
Units: Subjects
Abnormal	32	32
Normal	210	210
Missing	4	4
Lactate dehydrogenase (LDH) at Day 1
Units: Subjects
Abnormal	14	14
Normal	87	87
Missing	145	145

End points

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Reporting group title

BEP(500)

Reporting group description

BEP(500) chemotherapy was given as follows: bleomycin 30,000 IU day 1, cisplatin 50 mg/m2 days 1 + 2, etoposide 165 mg/m2 days 1, 2 + 3 followed by bleomycin 30,000 IU days 8 + 15

Subject analysis set title

Mock arm

Subject analysis set type

Intention-to-treat

Subject analysis set description

test to report single arm trial

Primary: Malignant recurrence rate at 2 years

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End point title

Malignant recurrence rate at 2 years

End point description

The study is aiming to demonstrate that one cycle of adjuvant BEP (500) reduces the 2 year malignant recurrence rate to less than 5% in high-risk (vascular invasion positive) stage 1 NSGCTT. Malignant recurrence is defined as any of the following: • Progressive rise in tumour markers requiring treatment (AFP and/or HCG from 2 consecutive results taken a week apart that have shown at least a 50% increase above the ULN). • Development of metastases on clinical examination or imaging (CT scan and/or Chest X-ray). Disease related events were reviewed by at least 2 of the 111 recurrence reviewers who determined whether the event is a true recurrence. All disease related events were reviewed prospectively by the IDMC who confirmed whether the event counts as a primary endpoint malignant recurrence event.

End point type

Primary

End point timeframe

2 years

End point values	BEP(500)	Mock arm
Number of subjects analysed	236	236
Units: Events
Event - malignant recurrence	3	3

Exact binomial estimate - ITT population - 2 yrs

Statistical analysis description

The reported malignant recurrence rate at 2 years (and its 95% confidence interval) is estimated using exact probabilities in the subset of patients with complete 2-years fup (228)

Comparison groups

BEP(500) v Mock arm

Number of subjects included in analysis

472

Analysis specification

Pre-specified

Analysis type

other ^[1]

Method

Parameter type

Recurrence rate (%)

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

3.7

Notes
[1] - Estimation

KM estimate - ITT population - 2 yrs

Comparison groups

BEP(500) v Mock arm

Number of subjects included in analysis

472

Analysis specification

Pre-specified

Analysis type

other ^[2]

Method

Parameter type

Recurrence rate (%)

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

Notes
[2] - In the absence of complete data at 2 years of follow-up, the recurrence rate and its 95% confidence interval is also estimated using Kaplan-Meier method. Patients with incomplete data at 2 years of follow-up were censored at the date when last seen prior to 2 years of follow-up. Patients with non malignant recurrence with teratoma differentiated (TD) in retroperitoneal nodes or any other suspected event with no evidence of malignancy were censored at the date when their event was reported

Exact binomial estimate - PP population - 2 yrs

Statistical analysis description

The reported malignant recurrence rate at 2 years (and its 95% confidence interval) is estimated using exact probabilities in the subset of patients with complete 2-years fup (207).

Comparison groups

BEP(500) v Mock arm

Number of subjects included in analysis

472

Analysis specification

Pre-specified

Analysis type

other ^[3]

Method

Parameter type

Recurrence rate (%)

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

4.2

Notes
[3] - Estimation

KM estimate - PP population - 2 yrs

Statistical analysis description

In the absence of complete data at 2 years of follow-up, the recurrence rate and its 95% confidence interval is also estimated using Kaplan-Meier method. Patients with incomplete data at 2 years of follow-up were censored at the date when last seen prior to 2 years of follow-up. Patients with non malignant recurrence with teratoma differentiated (TD) in retroperitoneal nodes or any other suspected event with no evidence of malignancy were censored at the date when their event was reported

Comparison groups

BEP(500) v Mock arm

Number of subjects included in analysis

472

Analysis specification

Pre-specified

Analysis type

other ^[4]

Method

Parameter type

Recurrence rate (%)

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

4.4

Notes
[4] - Estimation

KM estimate - ITT population - 4 yrs

Comparison groups

BEP(500) v Mock arm

Number of subjects included in analysis

472

Analysis specification

Pre-specified

Analysis type

other ^[5]

Method

Parameter type

Recurrence rate (%)

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

4.6

Notes
[5] - Estimation

KM estimate - PP population - 4 years

Comparison groups

BEP(500) v Mock arm

Number of subjects included in analysis

472

Analysis specification

Pre-specified

Analysis type

other ^[6]

Method

Parameter type

Recurrence rate (%)

Point estimate

1.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

5.1

Notes
[6] - Estimation

Secondary: Relapse Free Survival

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End point title

Relapse Free Survival

End point description

Relapse free survival was defined as time from registration until first confirmed relapse of testicular cancer or death from any cause. Patients alive with no event were censored at the date when they were last seen and patients with a secondary primary prior to their recurrence were censored at the time point of the 2nd primary diagnosis.

End point type

Secondary

End point timeframe

2 and 4 years

End point values	BEP(500)	Mock arm
Number of subjects analysed	236	236
Units: Events	9	9

KM estimate - ITT population - 2 yrs

Statistical analysis description

Kaplan-Meier method was used to estimate relapse free survival rate at 2 and 4 years along with the 95% confidence interval.

Comparison groups

BEP(500) v Mock arm

Number of subjects included in analysis

472

Analysis specification

Pre-specified

Analysis type

other ^[7]

Method

Parameter type

Proportion free of event (%)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

93.8

upper limit

98.6

Notes
[7] - Estimation

KM estimate - ITT population - 4 yrs

Statistical analysis description

Kaplan-Meier method was used to estimate relapse free survival rate at 2 and 4 years along with the 95% confidence interval.

Comparison groups

BEP(500) v Mock arm

Number of subjects included in analysis

472

Analysis specification

Pre-specified

Analysis type

other ^[8]

Method

Parameter type

Proportion free of event (%)

Point estimate

96.1

Confidence interval

level

95%

sides

2-sided

lower limit

92.6

upper limit

Notes
[8] - Estimation

Secondary: Overall Survival

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End point title

Overall Survival

End point description

Overall survival analysis included all deaths from any cause. Time was measured from registration and patients with no event were censored at the date when they were last seen. There were three reported deaths; two occurred prior to and one after the 24 month follow up.

End point type

Secondary

End point timeframe

2 and 4 years

End point values	BEP(500)	Mock arm
Number of subjects analysed	236	236
Units: Events	3	3

KM estimate - ITT population - 2 yrs

Comparison groups

BEP(500) v Mock arm

Number of subjects included in analysis

472

Analysis specification

Pre-specified

Analysis type

other ^[9]

Method

Parameter type

Proportion alive (%)

Point estimate

99.1

Confidence interval

level

95%

sides

2-sided

lower limit

96.6

upper limit

99.8

Notes
[9] - Estimation

KM estimate - ITT population - 4 yrs

Comparison groups

BEP(500) v Mock arm

Number of subjects included in analysis

472

Analysis specification

Pre-specified

Analysis type

other ^[10]

Method

Parameter type

Proportion alive (%)

Point estimate

98.7

Confidence interval

level

95%

sides

2-sided

lower limit

95.7

upper limit

99.6

Notes
[10] - Estimation

Secondary: Contralateral second primary testicular germ cell malignancy rate

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End point title

Contralateral second primary testicular germ cell malignancy rate

End point description

End point type

Secondary

End point timeframe

2 years

Number of subjects analysed

Units: Events

No statistical analyses for this end point

Other pre-specified: Teratoma differentiated recurrence rate

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End point title

Teratoma differentiated recurrence rate

End point description

End point type

Other pre-specified

End point timeframe

2 and 4 years

End point values	BEP(500)	Mock arm
Number of subjects analysed	236	236
Units: Events
Recurrence event	3	3

KM ITT population - 2 year

Comparison groups

BEP(500) v Mock arm

Number of subjects included in analysis

472

Analysis specification

Pre-specified

Analysis type

other ^[11]

Method

Parameter type

Recurrence rate (%)

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

Notes
[11] - Estimation

KM ITT population - 4 year

Comparison groups

BEP(500) v Mock arm

Number of subjects included in analysis

472

Analysis specification

Pre-specified

Analysis type

other ^[12]

Method

Parameter type

Recurrence rate (%)

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

Notes
[12] - Estimation

Other pre-specified: Recurrence Rate (any type)

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End point title

Recurrence Rate (any type)

End point description

Includes Malignant or Teratoma differentiated events

End point type

Other pre-specified

End point timeframe

2 and 4 years

End point values	BEP(500)	Mock arm
Number of subjects analysed	236	236
Units: Events	7	7

KM estimate - ITT population - 2 yrs

Comparison groups

BEP(500) v Mock arm

Number of subjects included in analysis

472

Analysis specification

Pre-specified

Analysis type

other ^[13]

Method

Parameter type

Recurrence rate

Point estimate

2.6

Confidence interval

level

95%

sides

2-sided

lower limit

1.2

upper limit

5.7

Notes
[13] - Estimation

KM estimate - ITT population - 4 yrs

Comparison groups

BEP(500) v Mock arm

Number of subjects included in analysis

472

Analysis specification

Pre-specified

Analysis type

other ^[14]

Method

Parameter type

Recurrence rate

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

1.5

upper limit

6.3

Notes
[14] - Estimation

Adverse events

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Timeframe for reporting adverse events

From registration to trial and within 30 days of the last administration of chemotherapy (3 weeks treatment + 30 days), which is not unequivocally due to progression of disease.

Adverse event reporting additional description

Additionally, post-treatment delayed toxicities (not subject to expedited reporting) were described. AEs assessed by CTCAE v3 following BE500Px1, then every 2 mo until 6 mo, every 3 mo until 24 mo, every 4 mo during the third year, and every 6 mo during the fourth and fifth year.

Assessment type

Systematic

Dictionary name

CTCAE

Dictionary version

Reporting group title

On-treatment toxicity

Reporting group description

Reporting group title

Post-treatment delayed toxicity 2-12 months

Reporting group description

An emergent toxicity over the 2 to 12 month period is defined as a toxicity not present at end of treatment or a toxicity event already present at end of cycle and that worsens since end of treatment.

Reporting group title

Post-treatment delayed toxicity 18-24 months

Reporting group description

Toxicities collected at 18 and 24 months follow-up refer to seven pre-specified toxicity types and allows for four further toxicities to be reported at each visit.

Reporting group title

Post-treatment delayed toxicity 36-60 months

Reporting group description

Serious adverse events	On-treatment toxicity	Post-treatment delayed toxicity 2-12 months	Post-treatment delayed toxicity 18-24 months	Post-treatment delayed toxicity 36-60 months
Total subjects affected by serious adverse events
subjects affected / exposed	46 / 236 (19.49%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
number of deaths (all causes)	0	1	1	1
number of deaths resulting from adverse events	0	0	0	0
Investigations
Blood creatinine increased
subjects affected / exposed	1 / 236 (0.42%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Headache
subjects affected / exposed	2 / 236 (0.85%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Presyncope
subjects affected / exposed	2 / 236 (0.85%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Febrile neutropenia
subjects affected / exposed	17 / 236 (7.20%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	17 / 17	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Leukopenia
subjects affected / exposed	1 / 236 (0.42%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	9 / 236 (3.81%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	9 / 9	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	1 / 236 (0.42%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	4 / 236 (1.69%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	2 / 4	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	10 / 236 (4.24%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	10 / 10	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Hypersensitivity
subjects affected / exposed	1 / 236 (0.42%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 236 (0.42%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	1 / 236 (0.42%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	3 / 236 (1.27%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	3 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis
subjects affected / exposed	1 / 236 (0.42%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	3 / 236 (1.27%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	3 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Stomatitis
subjects affected / exposed	2 / 236 (0.85%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	4 / 236 (1.69%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	4 / 4	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	2 / 236 (0.85%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngeal inflammation
subjects affected / exposed	1 / 236 (0.42%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pleuritic pain
subjects affected / exposed	1 / 236 (0.42%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	1 / 236 (0.42%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Renal failure
subjects affected / exposed	2 / 236 (0.85%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	1 / 236 (0.42%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myalgia
subjects affected / exposed	1 / 236 (0.42%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Anorectal cellulitis
subjects affected / exposed	1 / 236 (0.42%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	1 / 236 (0.42%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	1 / 236 (0.42%)	0 / 236 (0.00%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	On-treatment toxicity	Post-treatment delayed toxicity 2-12 months	Post-treatment delayed toxicity 18-24 months	Post-treatment delayed toxicity 36-60 months
Total subjects affected by non serious adverse events
subjects affected / exposed	232 / 236 (98.31%)	91 / 236 (38.56%)	107 / 215 (49.77%)	98 / 207 (47.34%)
Investigations
Weight increased
subjects affected / exposed	18 / 236 (7.63%)	33 / 236 (13.98%)	27 / 215 (12.56%)	28 / 207 (13.53%)
occurrences all number	18	33	27	28
Nervous system disorders
Dysgeusia
subjects affected / exposed	69 / 236 (29.24%)	5 / 236 (2.12%)	3 / 215 (1.40%)	1 / 207 (0.48%)
occurrences all number	69	5	3	1
Lethargy
subjects affected / exposed	135 / 236 (57.20%)	31 / 236 (13.14%)	34 / 215 (15.81%)	31 / 207 (14.98%)
occurrences all number	135	31	34	31
Neuropathy peripheral
subjects affected / exposed	18 / 236 (7.63%)	21 / 236 (8.90%)	13 / 215 (6.05%)	15 / 207 (7.25%)
occurrences all number	18	21	13	15
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	78 / 236 (33.05%)	2 / 236 (0.85%)	5 / 215 (2.33%)	5 / 207 (2.42%)
occurrences all number	78	2	5	5
Leukopenia
subjects affected / exposed	103 / 236 (43.64%)	1 / 236 (0.42%)	4 / 215 (1.86%)	5 / 207 (2.42%)
occurrences all number	103	1	4	5
Neutropenia
subjects affected / exposed	96 / 236 (40.68%)	1 / 236 (0.42%)	5 / 215 (2.33%)	3 / 207 (1.45%)
occurrences all number	96	1	5	3
Thrombocytopenia
subjects affected / exposed	142 / 236 (60.17%)	1 / 236 (0.42%)	7 / 215 (3.26%)	2 / 207 (0.97%)
occurrences all number	142	1	7	2
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	17 / 236 (7.20%)	1 / 236 (0.42%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences all number	17	1	0	0
Ear and labyrinth disorders
Ototoxicity
subjects affected / exposed	61 / 236 (25.85%)	13 / 236 (5.51%)	2 / 215 (0.93%)	0 / 207 (0.00%)
occurrences all number	61	13	2	0
Tinnitus
subjects affected / exposed	0 / 236 (0.00%)	0 / 236 (0.00%)	16 / 215 (7.44%)	6 / 207 (2.90%)
occurrences all number	0	0	16	6
Gastrointestinal disorders
Constipation
subjects affected / exposed	41 / 236 (17.37%)	2 / 236 (0.85%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences all number	41	2	0	0
Diarrhoea
subjects affected / exposed	30 / 236 (12.71%)	13 / 236 (5.51%)	3 / 215 (1.40%)	0 / 207 (0.00%)
occurrences all number	30	13	3	0
Nausea
subjects affected / exposed	66 / 236 (27.97%)	2 / 236 (0.85%)	0 / 215 (0.00%)	1 / 207 (0.48%)
occurrences all number	66	2	0	1
Stomatitits
subjects affected / exposed	37 / 236 (15.68%)	1 / 236 (0.42%)	0 / 215 (0.00%)	0 / 207 (0.00%)
occurrences all number	37	1	0	0
Vomiting
subjects affected / exposed	30 / 236 (12.71%)	1 / 236 (0.42%)	1 / 215 (0.47%)	0 / 207 (0.00%)
occurrences all number	30	1	1	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	24 / 236 (10.17%)	21 / 236 (8.90%)	12 / 215 (5.58%)	8 / 207 (3.86%)
occurrences all number	24	21	12	8
Dyspnoea
subjects affected / exposed	27 / 236 (11.44%)	14 / 236 (5.93%)	10 / 215 (4.65%)	10 / 207 (4.83%)
occurrences all number	27	14	10	10
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	186 / 236 (78.81%)	14 / 236 (5.93%)	1 / 215 (0.47%)	0 / 207 (0.00%)
occurrences all number	186	14	1	0
Rash
subjects affected / exposed	20 / 236 (8.47%)	5 / 236 (2.12%)	0 / 215 (0.00%)	1 / 207 (0.48%)
occurrences all number	20	5	0	1
Skin hyperpigmentation
subjects affected / exposed	15 / 236 (6.36%)	7 / 236 (2.97%)	2 / 215 (0.93%)	0 / 207 (0.00%)
occurrences all number	15	7	2	0

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Were there any global substantial amendments to the protocol? Yes

28 Jun 2012

Changes have been made to the protocol, patient information sheet (PIS) and consent form in order to reflect local practices, bring the advice given on fathering a child in line with the SmPCs and increase the patients’ awareness of the sperm analysis which is conducted within the trial. The enclosed summary of proposed amendment document lists all of the amendments made to the protocol, PIS and consent form. A letter template which will be completed by centres and signed by the patient in order to request sperm analysis results is also enclosed. This new document has been written with the aim of increasing the quality of fertility data currently being reported to ICR-CTSU. The amendment also consists of the addition of two sites and the change of PI at two sites. There has also been an addition of a PIC which has been noted on the summary table for your information.

26 Aug 2014

This amendment is for an administrative change to the protocol whereby the definition of the end of study (section 14) has been amended to provide a single definition for the study end date.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

http://www.ncbi.nlm.nih.gov/pubmed/31901440

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Clinical Trial Results:
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)

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Secondary: Contralateral second primary testicular germ cell malignancy rate

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Clinical trials

Clinical Trial Results: 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)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Malignant recurrence rate at 2 years

Primary: Malignant recurrence rate at 2 years

Secondary: Relapse Free Survival

Secondary: Relapse Free Survival

Secondary: Overall Survival

Secondary: Overall Survival

Secondary: Contralateral second primary testicular germ cell malignancy rate

Secondary: Contralateral second primary testicular germ cell malignancy rate

Other pre-specified: Teratoma differentiated recurrence rate

Other pre-specified: Teratoma differentiated recurrence rate

Other pre-specified: Recurrence Rate (any type)

Other pre-specified: Recurrence Rate (any type)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
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)