Germ Cell TumorPhase 3P3BEPNCT02582697
Accelerated v's Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumours
A Phase 3 study testing Bleomycin (active name: Bleomycin Sulfate), Etoposide and Cisplatin in people with Germ Cell Tumor, run by University of Sydney at 56 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 11 to 50 years
- Conditions the study is for
- Germ Cell Tumor
- What is being tested?
- Bleomycin (active name: Bleomycin Sulfate), Etoposide and Cisplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 500 participants
- Where
- 56 sitesin 4 countries
- Study dates
- Feb 2014to 31 Dec 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 11 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age ≥ 11 years and ≤ 50 years on the date of randomisation
- 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
- Primary arising in testis, ovary, retro-peritoneum, or mediastinum
- Metastatic disease or non-testicular primary
- 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).
- Adequate bone marrow function with ANC ≥1.0 x 10^9/L, Platelet count ≥100 x 10^9/L
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- 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
- 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
- ECOG Performance Status of 0, 1, 2, or 3
- Study treatment both planned and able to start within 14 days of randomisation.
- Willing and able to comply with all study requirements, including treatment, timing and nature of required assessments
- Able to provide signed, written informed consent
Who cannot join
- 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)
- 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 hasb. non-seminoma by IGCCC criteria or stage IV malignant ovarian germ cell tumour 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). Acceptable regimens include cisplatin 20 mg/m2 days 1-2 and etoposide 100 mg/m2 days 1-2; carboplatin AUC 3 days 1-2 and etoposide 100 mg/m2 days 1-2; or baby-BOP.43 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.
- Significant cardiac disease resulting in inability to tolerate IV fluid hydration for cisplatin
- Significant co-morbid respiratory disease that contraindicates the use of bleomycin
- Peripheral neuropathy ≥ grade 2 or clinically significant sensorineural hearing loss or tinnitus
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- Concurrent illness, including severe infection that may jeopardize the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety
- Inadequate contraception. Men must use 2 effective methods of contraception, including use of a condom, during chemotherapy and for a year after completing chemotherapy.
- Known allergy or hypersensitivity to any of the study drugs
- 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.
Trial locations and contacts
56 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
56 sites in 4 countries
United States21 sites, 21 recruiting
- Recruiting
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland
Patricia Rice, 410-955-5222, willipa@jhmi.edu
Alan D Friedman
- Recruiting
Dana-Farber/Harvard Cancer Center
Boston, Massachusetts
Jayme Wilde, 617-632-3000, jayme_wilde@dfci.harvard.edu
Lindsay A Frazier
- Recruiting
Ann and Robert H Lurie Children's Hospital of Chicago
Chicago, Illinois
Yulissa Padilla, 312-227-4000, ypadilla@luriechildrens.org
Amy Leanne L Walz
- Recruiting
University of Illinois
Chicago, Illinois
Jenna Gustafson, 866-600-2273, jrgustaf@uic.edu
Dipti S Dighe
- Recruiting
Ohio State University Comprehensive Cancer Center
Columbus, Ohio
Adaleigh Staley, 614-292-6446, Adaleigh.Staley@osumc.edu
Paul J Monk
- Recruiting
Driscoll Children's Hospital
Corpus Christi, Texas
Crystal de los santos, 361-694-5000, crystal.delossantos@dchstx.org
Nkechi I Mba
- Recruiting
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75235
Jessica Quicano, 817-676-9968, jessica.quicano@childrens.com
Jonathan E Wickiser
- Recruiting
Kaiser Permanente Downey Medical Center
Downey, California
Jeanette Velez, 562-657-9000, Jeanette.X.Velez@kp.org
Robert M Cooper
- Recruiting
Loma Linda University Medical Center
Loma Linda, California
Gwen Hill, 909-558-4000, GAHill@llu.edu
Albert Kheradpour
- Recruiting
Miller Children's and Women's Hospital Long Beach
Long Beach, California
Karla Ledezma, 562-933-5437, kledezma@memorialcare.org
Jacqueline N Casillas
- Recruiting
Los Angeles General Medical Center
Los Angeles, California
Rubina Hassan, 323-409-1000, Rubina.Hassan@med.usc.edu
Anishka D'Souza
- Recruiting
USC / Norris Comprehensive Cancer Center
Los Angeles, California
Rubina Hassan, 323-865-3000, Rubina.Hassan@med.usc.edu
Anishka D'Souza
- Recruiting
Memorial Sloan Kettering Cancer Centre
New York, New York, 10065
Victoria Martorana, martorav@mskcc.org
Darren Feldman
- Recruiting
Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois
Angela Kenaga, 708-684-8000, Angela.Kenaga@aah.org
Rebecca E McFall
- Recruiting
Lucile Packard Children's Hospital Stanford University
Palo Alto, California
Kailee Tanaka, 650-723-5535, kltanaka@stanford.edu
Jay M Balagtas
- Recruiting
Stanford Cancer Institute Palo Alto
Palo Alto, California
Kristine Talavera, 650-498-6000, kriscima@stanford.edu
Sandy Srinivas
- Recruiting
Advocate Children's Hospital-Park Ridge
Park Ridge, Illinois
Rina Dimaso, 847-723-2210, Rina.Dimaso@aah.org
Rebecca E McFall
- Recruiting
Primary Children's Hospital
Salt Lake City, Utah
Michelle Grant, 801-662-4700, Michelle.Grant@imail.org
Matthew Dietz
- Recruiting
University of Texas Health Science Center at San Antonio
San Antonio, Texas
Frances Maldonado, 210-567-7000, MALDONADOF@uthscsa.edu
Aaron Jon J Sugalski
- Recruiting
Rady Children's Hospital - San Diego
San Diego, California
Anjali Sapkal, 858-576-1700, ASapkal@rchsd.org
William D Roberts
- Recruiting
Washington University School of Medicine
St Louis, Missouri
Tina Primeau, 314-362-5000, tprimeau@wustl.edu
Frederick S Huang
Australia20 sites, 18 recruiting
- Recruiting
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Hazel Bourke, hazel.bourke@health.sa.gov.au
Thean Hsiang Tan, hsiang.tan@health.sa.gov.au
- Active, not recruiting
Flinders Medical Centre
Bedford Park, South Australia, 5042
- Recruiting
Box Hill Hospital
Box Hill, Victoria, 3128
Lauren Mitchell, lauren.mitchell@monash.edu
Ian Davis, Ian.Davis@monash.edu
- Recruiting
Royal Brisbane & Women's Hospital
Brisbane, Queensland, 4029
Natasha Roberts, natasha.roberts@health.qld.gov.au
David Wyld, david.wyld@health.qld.gov.au
- Recruiting
Peter MacCallum Cancer Centre
East Melbourne, Victoria, 3002
Jennifer Petersen, jennifer.petersen@petermac.org
Ben Tran, ben.tran@petermac.org
- Recruiting
Austin Health
Heidelberg, Victoria, 3084
Jaren Caine, Jaren.Caine@austin.org.au
Andrew Weickhardt, Andrew.Weickhardt@ludwig.edu.au
- Recruiting
Royal Hobart Hospital
Hobart, Tasmania, 7000
Lesley Oliver, lesley.oliver@dhhs.tas.gov.au
Rebecca Tay, rebecca.tay@ths.tas.gov.au
- Recruiting
Fiona Stanley Hospital
Murdoch, Western Australia, 6847
Jaye Harding, jaye.harding@health.wa.gov.au
Simon Troon, simon.troon@health.wa.gov.au
- Recruiting
Calvary Mater Newcastle
Newcastle, New South Wales, 2298
Louise Plowman, Louise.Plowman@calvarymater.org.au
Girish Mallesara, girish.mallesara@calvarymater.org.au
- Recruiting
Queensland Children's Hospital
South Brisbane, Queensland, 4101
Rick Walker, 'Rick.Walker@health.qld.gov.au'
Rick Walker
- Withdrawn
Sunshine Hospital
St Albans, Victoria, 3021
- Recruiting
Royal North Shore Hospital
St Leonards, New South Wales, 2065
Susan Kirby-Lewis, Susan.KirbyLewis@health.nsw.gov.au
Alexander Guminski, aguminski@nsccahs.health.nsw.gov.au
- Recruiting
Prince of Wales Hospital
Sydney, New South Wales, 2031
Daisy Buchanan, Daisy.buchanan@sesiahs.health.nsw.gov.au
Julie Howard, Julie.howard@sesiahs.health.nsw.gov.au
- Recruiting
Chris O'Brien Lifehouse
Sydney, New South Wales, 2050
Melissa Quaggiott, melissa.mcmahon@lh.org.au
Peter Grimison, peter.grimison@lh.org.au
- Recruiting
Macquarie Cancer Clinical Trials
Sydney, New South Wales, 2109
Louise Francisco, louise.francisco@mq.edu.au
Radhika Butala, radhika.butala@mq.edu.au
- Recruiting
Concord Repatriation General Hospital
Sydney, New South Wales, 2139
Kathy Hall, Kathy.Hall@sswahs.nsw.gov.au
Martin Stockler, martin.stockler@sydney.edu.au
- Recruiting
Nepean Hospital
Sydney, New South Wales, 2751
Jeremy Jones, jeremy.jones@swahs.health.nsw.gov.au
Amanda Stevanovic, amanda.stevanovic@swahs.health.nsw.gov.au
- Recruiting
SAN Clinical Trials Unit
Wahroonga, New South Wales, 2076
James McQuilan, James.McQuillan@sah.org.au
Gavin Marx, gmarx@nhog.com.au
- Recruiting
Border Medical Oncology
Wodonga, Victoria, 3690
Lauren Callow, lcallow@bordermedonc.com.au
Craig Underhill, cunderhill@bordermedonc.com.au
- Recruiting
Princess Alexandra
Woolloongabba, Queensland, 4102
Paul Baxter, Paul.Baxter@health.qld.gov.au
Euan Walpole, Euan.Walpole@health.qld.gov.au
United Kingdom10 sites, 10 recruiting
- Recruiting
Belfast City Hospital
Belfast, Northern Ireland
Chyrelle Mcalister, 44 (0)28 9032 9241, chyrelle.mcalister@belfasttrust.hscni.net
Bode Oladipo
- Recruiting
Cambridge University Hosptial
Cambridge, England
Amanda Walker, 44 (0)1223 245 151, amanda.walker11@nhs.net
Danish Mazhar
- Recruiting
Velindre Hospital
Cardiff, South East Wales
Sonya Osborne, 44 (0)29 2061 5888, sonya.osborne@wales.nhs.uk
Satish Kumar
- Recruiting
Beatson West of Scotland Cancer Centre
Glasgow, Scotland
Gurivine Kooner, 44 (0)141 301 7000, gurivine.kooner@nhs.scot
Jeffery White
- Recruiting
Royal Preston Hospital, Lancashire
Lancaster, England
Catherine Walmsley, 44 (0)1772 716 565, catherine.walmsley@lthtr.nhs.uk
Alison Birtle
- Recruiting
St James's University Hospital, Leeds
Leeds, West Yorkshire
Lam Cao, 44 (0)113 243 3144, lam.cao@nhs.net
Elaine Dunwoodle
- Recruiting
St Bartholomew's Hospital
London, England
Gouri Santhakumar, 44 (0)20 7377 7000, g.santhakumar@nhs.net
Jonathan Shamash
- Recruiting
The Royal Marsden Hospital
London, England
Ella Hallwood, 44 (0)20 7352 8171, ella.hallwood@rmh.nhs.uk
Robert Huddart
- Recruiting
University College Hospital, London
London, England
Ilhan Nur, 44 (0)20 3456 7890, ilhan.nur@nhs.net
Sara Stoneham
- Recruiting
University Hospital Southampton
Southampton, England
Rachel Burnish, 44 (0)23 8077 7222, Rachel.Burnish@uhs.nhs.uk
Matthew Wheater
New Zealand5 sites, 4 recruiting
- Recruiting
Christchurch Hospital
Christchurch, 8011
Elizabeth Thompson, liz.thompson@cdhb.health.nz
Mark Jeffrey, Mark.jeffery@cdhb.health.nz
- Withdrawn
Dunedin Hospital
Dunedin, 9054
- Recruiting
Starship Children's Hospital
Grafton, Auckland, 1023
Mark Winstanley, 'mwinstanley@adhb.govt.nz'
Mark Winstanley
- Recruiting
Auckland Hospital
Grafton, Auckland, 1142
Andrew Conley, andrewcon@adhb.govt.nz
Fritha Hanning, FrithaH@adhb.govt.nz
- Recruiting
Palmerston North Hospital
Roslyn, Palmerston North, 4442
Sarah Holwell, Sarah.Holwell@midcentraldhb.govt.nz
Gary Forgeson, Garry.Forgeson@midcentraldhb.govt.nz
About this study
Official 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
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.
Read the detailed description
Bleomycin, Etoposide, Cisplatin (BEP) administered 3-weekly x 4 remains standard 1st line chemotherapy for intermediate- and poor-risk metastatic germ cell tumours (GCTs). Cure rates are over 90% for good-risk disease, 85% with intermediate-risk, and about 70% for poor-risk disease. Previous strategies to improve first-line chemotherapy have failed to improve cure rates and were more toxic than BEP. New strategies are needed for patients with intermediate and poor-risk disease. BEP is accelerated by cycling Cisplatin and etoposide 2-weekly instead of 3-weekly. The Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) is conducting a trial comparing accelerated BEP with standard BEP. The aim of this study is to determine if accelerated BEP is superior to standard BEP as first-line chemotherapy for intermediate and poor risk metastatic GCTs.
- Conditions
- Germ Cell Tumor
- Being tested
- Bleomycin (active name: Bleomycin Sulfate), Etoposide, Cisplatin, Pegylated G-CSF (Pegfilgrastim), Filgrastim
- Keywords
- Germ Cell, Intermediate and poor-risk metastatic germ cell tumours
- Medical subject headings
- Neoplasms, Germ Cell and Embryonal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bleomycin (active name: Bleomycin Sulfate)Drug
Also called Blenamax (Aspen), DBL Bleomycin Sulphate (Willow Pharmaceuticals Pty Limited), Bleo Powder for injection (Hospira)
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.
EtoposideDrug
Also called DBL Etoposide Injection (Hospira), Etopophos (Bristol-Myers Squibb), Etoposide (Pfizer), Etoposide Ebewe (Sandoz)
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.
CisplatinDrug
Also called Cisplatin Ebewe (Sandoz), Cisplatin injection (Pfizer), DBL Cisplatin Injection (Hospira)
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.
Pegylated G-CSF (Pegfilgrastim)Drug
Also called Neulasta Syringe with Automatic Needle Guard (Amgen)
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.
FilgrastimDrug
Also called Neupogen (Amgen), Nivestim (Hospira), Tevagrastim (Teva Pharma Australia Pty Ltd), Zarzio (Sandoz)
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.
| Study group | Role | What they receive |
|---|---|---|
| Standard Arm - Standard BEP | Active comparator | 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. Receives: Drug: Bleomycin (active name: Bleomycin Sulfate); Drug: Etoposide; Drug: Cisplatin; Drug: Pegylated G-CSF (Pegfilgrastim); Drug: Filgrastim |
| Experimental Arm - Accelerated BEP | Experimental | 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. Receives: Drug: Bleomycin (active name: Bleomycin Sulfate); Drug: Etoposide; Drug: Cisplatin; Drug: Pegylated G-CSF (Pegfilgrastim); Drug: Filgrastim |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: From randomisation up to disease progression or date of death whichever come first, assessed up to 5 years
Secondary outcomes (8)
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.
Measured: At end of chemotherapy treatment, treatment planned for 12 weeks
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.
Measured: At 6 months
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)
Measured: From start of chemotherapy until 30 days after last dose, an average of 4 months
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.
Measured: From date of randomisation until date of 18 month follow-up
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.
Measured: From date of randomisation until date of 18 month follow-up
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.
Measured: From date of randomisation until date of 18 month follow-up
Delivered dose-intensity of chemotherapy (relative to standard BEP)
Delivered dose-intensity of cisplatin, etoposide and bleomycin will be assessed.
Measured: From start date of chemotherapy treatment until date of end of chemotherapy, an average of 12 weeks
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.
Measured: From randomisation up to disease progression or date of death whichever come first, assessed up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2015 (estimated)
- Study startFeb 2014
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Germ Cell TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sydney
- Sponsor type
- University, hospital or other
- Collaborators
- Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Cambridge University Hospitals NHS Foundation Trust, Cancer Trials Ireland, Children's Oncology Group, Dana-Farber Cancer Institute, University of Southern California
- Responsible party
- Sponsor
- Investigators
- Peter Grimison, Study chair, Chris O'Brien Lifehouse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02582697
- Sponsor's protocol ID
- ANZUP1302
- Other IDs
- ACTRN12613000496718
- Acronym
- P3BEP
- Status last verified
- Aug 2026
- First submitted
- 7 Sep 2015
- Last updated
- 1 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lawrence NJ, Chan H, Toner G, Stockler MR, Martin A, Yip S, Wong N, Yeung A, Mazhar D, Pashankar F, Frazier L, McDermott R, Walker R, Tan H, Davis ID, Grimison P; ANZUP. Protocol for the P3BEP trial (ANZUP 1302): an international randomised phase 3 trial of accelerated versus standard BEP chemotherapy for adult and paediatric male and female patients with intermediate and poor-risk metastatic germ cell tumours. BMC Cancer. 2018 Aug 29;18(1):854. doi: 10.1186/s12885-018-4745-3.
PubMed 30157803
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02582697
- Acronym / sponsor ID
- P3BEP / ANZUP1302
- Conditions
- Germ Cell Tumor
- Keywords
- Germ Cell, Intermediate and poor-risk metastatic germ cell tumours
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- University of SydneyUniversity, hospital or other
- Collaborators
- Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Cambridge University Hospitals NHS Foundation Trust, Cancer Trials Ireland, Children's Oncology Group, Dana-Farber Cancer Institute, University of Southern California
- Study start
- Feb 2014 (actual)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 21 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Bleomycin, Etoposide, Cisplatin (BEP) administered 3-weekly x 4 remains standard 1st line chemotherapy for intermediate- and poor-risk metastatic germ cell tumours (GCTs). Cure rates are over 90% for good-risk disease, 85% with intermediate-risk, and about 70% for poor-risk disease. Previous strategies to improve first-line chemotherapy have failed to improve cure rates and were more toxic than BEP. New strategies are needed for patients with intermediate and poor-risk disease. BEP is accelerated by cycling Cisplatin and etoposide 2-weekly instead of 3-weekly. The Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) is conducting a trial comparing accelerated BEP with standard BEP. The aim of this study is to determine if accelerated BEP is superior to standard BEP as first-line chemotherapy for intermediate and poor risk metastatic GCTs.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Arm - Standard BEP | Active comparator | Drug: Bleomycin (active name: Bleomycin Sulfate), Drug: Etoposide, Drug: Cisplatin, Drug: Pegylated G-CSF (Pegfilgrastim), Drug: FilgrastimParticipants 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 Arm - Accelerated BEP | Experimental | Drug: Bleomycin (active name: Bleomycin Sulfate), Drug: Etoposide, Drug: Cisplatin, Drug: Pegylated G-CSF (Pegfilgrastim), Drug: FilgrastimParticipants 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. |
Who may qualify
- Ages
- 11 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- Age ≥ 11 years and ≤ 50 years on the date of randomisation
- 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
- Primary arising in testis, ovary, retro-peritoneum, or mediastinum
- Metastatic disease or non-testicular primary
- 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).
Key exclusion criteria (11 listed)
- 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)
- 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 hasb. non-seminoma by IGCCC criteria or stage IV malignant ovarian germ cell tumour 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). Acceptable regimens include cisplatin 20 mg/m2 days 1-2 and etoposide 100 mg/m2 days 1-2; carboplatin AUC 3 days 1-2 and etoposide 100 mg/m2 days 1-2; or baby-BOP.43 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.
- Significant cardiac disease resulting in inability to tolerate IV fluid hydration for cisplatin
- Significant co-morbid respiratory disease that contraindicates the use of bleomycin
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bleomycin (active name: Bleomycin Sulfate)Also: Blenamax (Aspen), DBL Bleomycin Sulphate (Willow Pharmaceuticals Pty Limited), Bleo Powder for injection (Hospira)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. | Drug | Experimental Arm - Accelerated BEP, Standard Arm - Standard BEP |
| EtoposideAlso: DBL Etoposide Injection (Hospira), Etopophos (Bristol-Myers Squibb), Etoposide (Pfizer), Etoposide Ebewe (Sandoz)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. | Drug | Experimental Arm - Accelerated BEP, Standard Arm - Standard BEP |
| CisplatinAlso: Cisplatin Ebewe (Sandoz), Cisplatin injection (Pfizer), DBL Cisplatin Injection (Hospira)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. | Drug | Experimental Arm - Accelerated BEP, Standard Arm - Standard BEP |
| Pegylated G-CSF (Pegfilgrastim)Also: Neulasta Syringe with Automatic Needle Guard (Amgen)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. | Drug | Experimental Arm - Accelerated BEP, Standard Arm - Standard BEP |
| FilgrastimAlso: Neupogen (Amgen), Nivestim (Hospira), Tevagrastim (Teva Pharma Australia Pty Ltd), Zarzio (Sandoz)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. | Drug | Experimental Arm - Accelerated BEP, Standard Arm - Standard BEP |
Primary outcome
Progression-free survival (disease progression or death)
Time frame: From randomisation up to disease progression or date of death whichever come first, assessed up to 5 years
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
8 secondary outcomes
Initial response assessment
Time frame: At end of chemotherapy treatment, treatment planned for 12 weeks
Final response assessment
Time frame: At 6 months
Adverse events (worst grade according to NCI CTCAE v4.03)
Time frame: From start of chemotherapy until 30 days after last dose, an average of 4 months
Health-related quality of life
Time frame: From date of randomisation until date of 18 month follow-up
Health-related quality of life for testicular cancer
Time frame: From date of randomisation until date of 18 month follow-up
Treatment preference
Time frame: From date of randomisation until date of 18 month follow-up
Delivered dose-intensity of chemotherapy (relative to standard BEP)
Time frame: From start date of chemotherapy treatment until date of end of chemotherapy, an average of 12 weeks
Overall survival
Time frame: From randomisation up to disease progression or date of death whichever come first, assessed up to 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2026.
- Derived from this study: PubMed 30157803Lawrence NJ, Chan H, Toner G, Stockler MR, Martin A, Yip S, Wong N, Yeung A, Mazhar D, Pashankar F, Frazier L, McDermott R, Walker R, Tan H, Davis ID, Grimison P; ANZUP. Protocol for the P3BEP trial (ANZUP 1302): an international randomised phase 3 trial of accelerated versus standard BEP chemotherapy for adult and paediatric male and female patients with intermediate and poor-risk metastatic germ cell tumours. BMC Cancer. 2018 Aug 29;18(1):854. doi: 10.1186/s12885-018-4745-3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Peter Grimison study chair
Chris O'Brien Lifehouse
56 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Bleomycin (active name: Bleomycin Sulfate), Etoposide and Cisplatin in people with Germ Cell Tumor, run by University of Sydney at 56 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 56 sites in United States, Australia, United Kingdom, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact P3BEP Trial Coordinator (+6195625000 ext. 5000, p3bep.study@sydney.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (disease progression or death) (time frame: From randomisation up to disease progression or date of death whichever come first, assessed up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02582697, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.