Accelerated v's Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumours

NCT ID: NCT02582697

Last Updated: 2025-06-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-02-28

Study Completion Date

2029-12-31

Brief Summary

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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

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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

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Germ Cell Tumor

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Bleomycin (active name: Bleomycin Sulfate)

Intervention Type DRUG

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.

Etoposide

Intervention Type DRUG

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.

Cisplatin

Intervention Type DRUG

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)

Intervention Type DRUG

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.

Filgrastim

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

Bleomycin (active name: Bleomycin Sulfate)

Intervention Type DRUG

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.

Etoposide

Intervention Type DRUG

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.

Cisplatin

Intervention Type DRUG

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)

Intervention Type DRUG

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.

Filgrastim

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

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.

Intervention Type DRUG

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.

Intervention Type DRUG

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 Type DRUG

Other Intervention Names

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Blenamax (Aspen) DBL Bleomycin Sulphate (Willow Pharmaceuticals Pty Limited) Bleo Powder for injection (Hospira) DBL Etoposide Injection (Hospira) Etopophos (Bristol-Myers Squibb) Etoposide (Pfizer) Etoposide Ebewe (Sandoz) Cisplatin Ebewe (Sandoz) Cisplatin injection (Pfizer) DBL Cisplatin Injection (Hospira) Neulasta Syringe with Automatic Needle Guard (Amgen) Neupogen (Amgen) Nivestim (Hospira) Tevagrastim (Teva Pharma Australia Pty Ltd) Zarzio (Sandoz)

Eligibility Criteria

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Inclusion Criteria

1. Age ≥ 11 years and ≤ 50 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

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)

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
Minimum Eligible Age

11 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Australian and New Zealand Urogenital and Prostate Cancer Trials Group

OTHER

Sponsor Role collaborator

Cambridge University Hospitals NHS Foundation Trust

OTHER

Sponsor Role collaborator

Cancer Trials Ireland

NETWORK

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role collaborator

University of Southern California

OTHER

Sponsor Role collaborator

University of Sydney

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Peter Grimison

Role: STUDY_CHAIR

Chris O'Brien Lifehouse

Locations

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Memorial Sloan Kettering Cancer Centre

New York, New York, United States

Site Status RECRUITING

Calvary Mater Newcastle

Newcastle, New South Wales, Australia

Site Status RECRUITING

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Site Status RECRUITING

Prince of Wales Hospital

Sydney, New South Wales, Australia

Site Status RECRUITING

Chris O'Brien Lifehouse

Sydney, New South Wales, Australia

Site Status RECRUITING

Macquarie Cancer Clinical Trials

Sydney, New South Wales, Australia

Site Status RECRUITING

Concord Repatriation General Hospital

Sydney, New South Wales, Australia

Site Status RECRUITING

Westmead Hospital

Sydney, New South Wales, Australia

Site Status WITHDRAWN

Nepean Hospital

Sydney, New South Wales, Australia

Site Status RECRUITING

Tweed Hospital

Tweed Heads, New South Wales, Australia

Site Status RECRUITING

SAN Clinical Trials Unit

Wahroonga, New South Wales, Australia

Site Status RECRUITING

Royal Brisbane & Women's Hospital

Brisbane, Queensland, Australia

Site Status RECRUITING

Queensland Children's Hospital

South Brisbane, Queensland, Australia

Site Status RECRUITING

Princess Alexandra

Woolloongabba, Queensland, Australia

Site Status RECRUITING

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status RECRUITING

Flinders Medical Centre

Bedford Park, South Australia, Australia

Site Status ACTIVE_NOT_RECRUITING

Royal Hobart Hospital

Hobart, Tasmania, Australia

Site Status RECRUITING

Box Hill Hospital

Box Hill, Victoria, Australia

Site Status RECRUITING

Peter MacCallum Cancer Centre

East Melbourne, Victoria, Australia

Site Status RECRUITING

Austin Health

Heidelberg, Victoria, Australia

Site Status RECRUITING

Sunshine Hospital

St Albans, Victoria, Australia

Site Status WITHDRAWN

Border Medical Oncology

Wodonga, Victoria, Australia

Site Status RECRUITING

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Site Status RECRUITING

Starship Children's Hospital

Grafton, Auckland, New Zealand

Site Status RECRUITING

Auckland Hospital

Grafton, Auckland, New Zealand

Site Status RECRUITING

Palmerston North Hospital

Roslyn, Palmerston North, New Zealand

Site Status RECRUITING

Christchurch Hospital

Christchurch, , New Zealand

Site Status RECRUITING

Dunedin Hospital

Dunedin, , New Zealand

Site Status WITHDRAWN

Countries

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United States Australia New Zealand

Central Contacts

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P3BEP Trial Coordinator

Role: CONTACT

+6195625000 ext. 5000

P3BEP Project Manager

Role: CONTACT

+6195625000 ext. 5000

Facility Contacts

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Victoria Martorana

Role: primary

Louise Plowman

Role: primary

Girish Mallesara

Role: backup

Susan Kirby-Lewis

Role: primary

Alexander Guminski

Role: backup

Daisy Buchanan

Role: primary

Julie Howard

Role: backup

Melissa Quaggiott

Role: primary

Peter Grimison

Role: backup

Louise Francisco

Role: primary

Radhika Butala

Role: backup

Kathy Hall

Role: primary

Martin Stockler

Role: backup

Jeremy Jones

Role: primary

Amanda Stevanovic

Role: backup

Charmayne Chorlton

Role: primary

Ratnesh Srivastav

Role: backup

James McQuilan

Role: primary

Gavin Marx

Role: backup

Natasha Roberts

Role: primary

David Wyld

Role: backup

Rick Walker

Role: primary

Paul Baxter

Role: primary

Euan Walpole

Role: backup

Hazel Bourke

Role: primary

Thean Hsiang Tan

Role: backup

Lesley Oliver

Role: primary

Rebecca Tay

Role: backup

Lauren Mitchell

Role: primary

Ian Davis

Role: backup

Jennifer Petersen

Role: primary

Ben Tran

Role: backup

Jaren Caine

Role: primary

Andrew Weickhardt

Role: backup

Lauren Callow

Role: primary

Craig Underhill

Role: backup

Jaye Harding

Role: primary

Simon Troon

Role: backup

Mark Winstanley

Role: primary

Andrew Conley

Role: primary

Fritha Hanning

Role: backup

Sarah Holwell

Role: primary

Gary Forgeson

Role: backup

Elizabeth Thompson

Role: primary

Mark Jeffrey

Role: backup

References

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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.

Reference Type DERIVED
PMID: 30157803 (View on PubMed)

Other Identifiers

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ACTRN12613000496718

Identifier Type: REGISTRY

Identifier Source: secondary_id

ANZUP1302

Identifier Type: -

Identifier Source: org_study_id

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