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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02582697




Registration number
NCT02582697
Ethics application status
Date submitted
7/09/2015
Date registered
21/10/2015
Date last updated
11/07/2017

Titles & IDs
Public title
Accelerated v's Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumours
Scientific title
Phase 3 Accelerated BEP: A Randomised Phase 3 Trial of Accelerated Versus Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumours
Secondary ID [1] 0 0
ACTRN12613000496718
Secondary ID [2] 0 0
ANZUP1302
Universal Trial Number (UTN)
Trial acronym
P3BEP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Germ Cell Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Testicular
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bleomycin (active name: Bleomycin Sulfate)
Treatment: Drugs - Etoposide
Treatment: Drugs - Cisplatin
Treatment: Drugs - Pegylated G-CSF (Pegfilgrastim)
Treatment: Drugs - Filgrastim

Active Comparator: Standard Arm - Standard BEP - Participants 16 years or older will receive 4 cycles of Standard BEP as follows:
Bleomycin 30,000 IU IV weekly for 3 doses
Etoposide 100 mg/m2 IV on day 1 - 5
Cisplatin 20 mg/m2 IV on day 1 - 5
Pegylated G-CSF 6 mg SCI on day 6
Patients < 16 years old and weighs = 45 kg will receive:
Bleomycin *15,000 - 30,000 IU IV weekly for 3 doses
Etoposide 100 mg/m2 IV on day 1 - 5
Cisplatin 20 mg/m2 IV on day 1 - 5
Pegylated G-CSF 6 mg SCI on day 6
Patients <16 years old and weighs < 45 kg will receive:
Bleomycin *15,000 - 30,000 IU IV weekly for 3 doses
Etoposide 100 mg/m2 IV on day 1 - 5
Cisplatin 20 mg/m2 IV on day 1 - 5
Filgrastim 10mcg/kg/day on day 6, until post-nadir Absolute Neutrophil Count =1 x10^9/ L
The dose of bleomycin is decided by the treating physician and based on the patient's Body Surface Area.
Each cycle is 3 weeks (21 days).
The planned total duration of treatment is 12 weeks.

Experimental: Experimental Arm - Accelerated BEP - Participants 16years or older will receive 4 cycles of Accelerated BEP as follows:
Bleomycin 30,000 IU IV wkly for 2 doses
Etoposide 100 mg/m2 IV on day 1 - 5
Cisplatin 20 mg/m2 IV on day 1- 5
Pegylated G-CSF 6 mg SCI on day 6
Patients <16years and weighs =45 kg will receive:
Bleomycin *15,000 - 30,000 IU IV wkly for 2 doses
Etoposide 100 mg/m2 IV on day 1 - 5
Cisplatin 20 mg/m2 IV on day 1 - 5
Pegylated G-CSF 6 mg SCI on day 6
Patients <16years and weighs <45 kg will receive:
Bleomycin *15,000 - 30,000 IU IV wkly for 2 doses
Etoposide 100 mg/m2 IV on day 1 - 5
Cisplatin 20 mg/m2 IV on day 1 - 5
Filgrastim 10mcg/kg/day on day 6, until ANC =1 x10^9/ L
Each cycle is 2 weeks (14days)
Following 4xBEP cycles, patients will receive additional bleomycin as follows:
- Bleomycin *15,000 - 30,000 IU IV wkly for 4 doses
* The dose of bleomycin is decided by the treating physician and based on the patient's BSA.
The planned total duration is 12 weeks.


Treatment: Drugs: Bleomycin (active name: Bleomycin Sulfate)
Standard Arm: Bleomycin 30,000 international units IV weekly for 3 doses (eg. days 1, 8 and 15 or days 2, 9 and 16 of a 21-day cycle) for 4 cycles.
Accelerated Arm: Bleomycin 30,000 international units IV weekly for 2 doses (eg. days 1 and 8 or days 2 and 9 of a 14-day cycle) for 4 cycles. Followed by Bleomycin 30,000 international units IV weekly for 4 doses.

Treatment: Drugs: Etoposide
Standard Arm: Etoposide 100 mg/m2 IV on days 1, 2, 3, 4, 5 of a 21-day cycle for 4 cycles.
Accelerated Arm: 100 mg/m2 IV on days 1, 2, 3, 4, 5 of a 14-day cycle for 4 cycles.

Treatment: Drugs: Cisplatin
Standard Arm: Cisplatin 20 mg/m2 IV on days 1, 2, 3, 4, 5 of a 21-day cycle for 4 cycles.
Accelerated Arm: Cisplatin 20 mg/m2 IV on days 1, 2, 3, 4, 5 of a 14-day cycle for 4 cycles.

Treatment: Drugs: Pegylated G-CSF (Pegfilgrastim)
Standard Arm: 6 mg SCI on day 6 of a 21-day cycle for 4 cycles. Accelerated Arm: 6 mg SCI on day 6 of a 14-day cycle for 4 cycles.

Treatment: Drugs: Filgrastim
Standard Arm: 10 mcg/kg/day on day6, until post-nadir absolute neutrophil count = 1.0 x 10^9/L, of a 21-day cycle for 4 cycles.
Accelerated Arm: 10 mcg/kg/day on day 6, until post-nadir absolute neutrophil count = 1.0 x 10^9/L, of a 14-day cycle for 4 cycles.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (disease progression or death) - PFS is measured from the date of randomisation until the criteria for disease progression are met (as defined in the protocol) or death. Participants who are not observed to progress nor die will be censored at the date of last follow-up
Timepoint [1] 0 0
From randomisation up to disease progression or date of death whichever come first, assessed up to 5 years
Secondary outcome [1] 0 0
Initial response assessment - The assessment of response of germ cell tumours is measured by the change in size of measurable tumour masses in combination with changes in serum tumour markers after chemotherapy treatment.
Timepoint [1] 0 0
At end of chemotherapy treatment, treatment planned for 12 weeks
Secondary outcome [2] 0 0
Final response assessment - The assessment of response of germ cell tumours is measured by changes in serum tumour markers and imaging at 6 months from randomisation, or after any post-chemotherapy surgical resection or other intervention, whichever occurs last.
Timepoint [2] 0 0
At 6 months
Secondary outcome [3] 0 0
Adverse events (worst grade according to NCI CTCAE v4.03) - The intensity of adverse events will be assessed using the NCI Common Terminology Criteria for Adverse Events version 4 (NCI CTCAE v4.03)
Timepoint [3] 0 0
From start of chemotherapy until 30 days after last dose, an average of 4 months
Secondary outcome [4] 0 0
Health-related quality of life - HR-QoL measures will include the EORTC core quality of life questionnaire (QLQ-C30), a 30-item cancer-specific questionnaire that is well-validated and available in many languages.
Timepoint [4] 0 0
From date of randomisation until date of 18 month follow-up
Secondary outcome [5] 0 0
Health-related quality of life for testicular cancer - EORTC quality of life module for testicular cancer (QLQ-TC26), a disease-specific measure with 26 items about physical symptoms, sexual functioning and emotional issues.
Timepoint [5] 0 0
From date of randomisation until date of 18 month follow-up
Secondary outcome [6] 0 0
Treatment preference - A trial-specific preferences question will be used to determine if participants think they would prefer to be treated with accelerated BEP or standard BEP, assuming that they were equally effective.
Timepoint [6] 0 0
From date of randomisation until date of 18 month follow-up
Secondary outcome [7] 0 0
Delivered dose-intensity of chemotherapy (relative to standard BEP) - Delivered dose-intensity of cisplatin, etoposide and bleomycin will be assessed.
Timepoint [7] 0 0
From start date of chemotherapy treatment until date of end of chemotherapy, an average of 12 weeks
Secondary outcome [8] 0 0
Overall survival - Overall survival is measured from the date of randomisation until death from any cause, or the date of last known follow-up alive.
Timepoint [8] 0 0
From randomisation up to disease progression or date of death whichever come first, assessed up to 5 years

Eligibility
Key inclusion criteria
1. Age = 11 years and = 45 years on the date of randomisation

2. Histologically or cytologically confirmed germ cell tumour (non-seminoma or seminoma);
or Exceptionally raised tumour markers (AFP = 1000ng/mL and/or HCG = 5000 IU/L)
without histologic or cytologic confirmation in the rare case where pattern of
metastases consistent with GCT, high tumour burden, and a need to start therapy
urgently

3. Primary arising in testis, ovary, retro-peritoneum, or mediastinum

4. Metastatic disease or non-testicular primary

5. Intermediate or poor prognosis as defined by IGCCC classification3 (modified with
different LDH criteria for intermediate risk non-seminoma, and inclusion of ovarian
primaries). (See protocol for more information).

6. Adequate bone marrow function with ANC =1.0 x 10^9/L, Platelet count =100 x 10^9/L

7. Adequate liver function where bilirubin must be =1.5 x ULN, except participants with
Gilbert's Syndrome where bilirubin must be =2.0 x ULN; ALT and AST must be =2.5 x ULN,
except if the elevations are due to hepatic metastases, in which case ALT and AST must
be = 5 x ULN

8. Adequate renal function with estimated creatinine clearance of =60 ml/min according to
the Cockcroft-Gault formula, unless calculated to be < 60 ml/min or borderline in
which case GFR should be formally measured, eg. with EDTA scan

9. ECOG Performance Status of 0, 1, 2, or 3

10. Study treatment both planned and able to start within 14 days of randomisation.

11. Willing and able to comply with all study requirements, including treatment, timing
and nature of required assessments

12. Able to provide signed, written informed consent
Minimum age
11 Years
Maximum age
45 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Other primary malignancy (EXCEPT adequately treated non-melanomatous carcinoma of the
skin, germ cell tumour, or other malignancy treated at least 5 years previously with
no evidence of recurrence)

2. Previous chemotherapy or radiotherapy, except if patient has pure seminoma relapsing
after adjuvant radiotherapy or adjuvant chemotherapy with 1-2 doses of single agent
carboplatin or if patient has non-seminoma and poor prognosis by IGCCC criteria in the
rare case where low-dose induction chemotherapy is given prior to registration because
patient is not fit enough to receive protocol chemotherapy (eg. organ failure, vena
cava obstruction, overwhelming burden of disease). In these instances acceptable
regimens include cisplatin 20 mg/m^2 days 1-2 and etoposide 100 mg/m^2 days 1-2;
carboplatin AUC 3 days 1-2 and etoposide 100 mg/m^2 days 1-2; or baby-BOP. Patients
must meet all other inclusion and exclusion criteria at the time of registration.

Additionally participants who need to start therapy urgently prior to completing
study-specific baseline investigations may commence study chemotherapy prior to
registration and randomisation. Such patients must be discussed with the coordinating
centre prior to registration, and must be registered within 10 days of commencing
study chemotherapy.

3. Significant cardiac disease resulting in inability to tolerate IV fluid hydration for
cisplatin

4. Significant co-morbid respiratory disease that contraindicates the use of bleomycin

5. Peripheral neuropathy = grade 2 or clinically significant sensorineural hearing loss
or tinnitus

6. Concurrent illness, including severe infection that may jeopardize the ability of the
participant to undergo the procedures outlined in this protocol with reasonable safety

7. Inadequate contraception. Men must use 2 effective methods of contraception, including
use of a condom, during chemotherapy and for a year after completing chemotherapy.

8. Known allergy or hypersensitivity to any of the study drugs

9. Presence of any psychological, familial, sociological or geographical condition that
in the opinion of the investigator would hamper compliance with the study protocol and
follow-up schedule, including alcohol dependence or drug abuse

The above inclusion and exclusion criteria will apply to stage 1 (n=150) and stage 2 (n=500
including stage 1) of the study. All sites will participate in both stages of the study
with the exception of the Children's Oncology Group who will be participate in stage 1
only.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Calvary Mater Newcastle - Newcastle
Recruitment hospital [2] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [3] 0 0
Prince of Wales Hospital - Sydney
Recruitment hospital [4] 0 0
Chris O'Brien Lifehouse - Sydney
Recruitment hospital [5] 0 0
Macquarie Cancer Clinical Trials - Sydney
Recruitment hospital [6] 0 0
Concord Repatriation General Hospital - Sydney
Recruitment hospital [7] 0 0
Westmead Hospital - Sydney
Recruitment hospital [8] 0 0
Nepean Hospital - Sydney
Recruitment hospital [9] 0 0
Tweed Hospital - Tweed Heads
Recruitment hospital [10] 0 0
SAN Clinical Trials Unit - Wahroonga
Recruitment hospital [11] 0 0
Royal Brisbane & Women's Hospital - Brisbane
Recruitment hospital [12] 0 0
Princess Alexandra - Woolloongabba
Recruitment hospital [13] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [14] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [15] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [16] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [17] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment hospital [18] 0 0
Austin Health - Heidelberg
Recruitment hospital [19] 0 0
Sunshine Hospital - St Albans
Recruitment hospital [20] 0 0
Border Medical Oncology - Wodonga
Recruitment hospital [21] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2298 - Newcastle
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
2031 - Sydney
Recruitment postcode(s) [4] 0 0
2050 - Sydney
Recruitment postcode(s) [5] 0 0
2109 - Sydney
Recruitment postcode(s) [6] 0 0
2139 - Sydney
Recruitment postcode(s) [7] 0 0
2145 - Sydney
Recruitment postcode(s) [8] 0 0
2751 - Sydney
Recruitment postcode(s) [9] 0 0
2485 - Tweed Heads
Recruitment postcode(s) [10] 0 0
2076 - Wahroonga
Recruitment postcode(s) [11] 0 0
4029 - Brisbane
Recruitment postcode(s) [12] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [13] 0 0
5000 - Adelaide
Recruitment postcode(s) [14] 0 0
5042 - Bedford Park
Recruitment postcode(s) [15] 0 0
7000 - Hobart
Recruitment postcode(s) [16] 0 0
3128 - Box Hill
Recruitment postcode(s) [17] 0 0
3002 - East Melbourne
Recruitment postcode(s) [18] 0 0
3084 - Heidelberg
Recruitment postcode(s) [19] 0 0
3021 - St Albans
Recruitment postcode(s) [20] 0 0
3690 - Wodonga
Recruitment postcode(s) [21] 0 0
6847 - Murdoch
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Palmerston North
Country [3] 0 0
New Zealand
State/province [3] 0 0
Christchurch
Country [4] 0 0
New Zealand
State/province [4] 0 0
Dunedin

Funding & Sponsors
Primary sponsor type
Other
Name
University of Sydney
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Cambridge University Hospitals NHS Foundation Trust
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Cancer Trials Ireland
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Children's Oncology Group
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Dana-Farber Cancer Institute
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
University of Southern California
Address [6] 0 0
Country [6] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine whether accelerated BEP chemotherapy is more
effective than standard BEP chemotherapy in males with intermediate and poor-risk metastatic
germ cell tumours.
Trial website
https://clinicaltrials.gov/show/NCT02582697
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Peter Grimison
Address 0 0
Chris O'Brien Lifehouse
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
P3BEP Trial Coordinator
Address 0 0
Country 0 0
Phone 0 0
+6195625000
Fax 0 0
Email 0 0
p3bep@ctc.usyd.edu.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02582697