Neoplasms

All Conditions

Rare Diseases

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Germ Cells Tumors

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Bleomycin

Etoposide

Cisplatin

Lenograstim

Etoposide phosphate

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

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.

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.

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.

Bleomycin (active name: Bleomycin Sulfate)

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.

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.

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.

Pegylated G-CSF (Pegfilgrastim)

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.

Filgrastim

P3BEP Trial Coordinator

P3BEP Project Manager

Victoria Martorana

Darren Feldman

Louise Plowman

Girish Mallesara

Susan Kirby-Lewis

Alexander Guminski

Daisy Buchanan

Julie Howard

Elizabeth Hovey

Melissa Quaggiott

Peter Grimison

Louise Francisco

Radhika Butala

Howard Gurney

Kathy Hall

Martin Stockler

Jeremy Jones

Amanda Stevanovic

Charmayne Chorlton

Ratnesh Srivastav

James McQuilan

Gavin Marx

Natasha Roberts

David Wyld

Rick Walker

Paul Baxter

Euan Walpole

Hazel Bourke

Thean Hsiang Tan

Thean Tan

Lesley Oliver

Rebecca Tay

Lauren Mitchell

Ian Davis

Jennifer Petersen

Ben Tran

Jaren Caine

Andrew Weickhardt

Lauren Callow

Craig Underhill

Jaye Harding

Simon Troon

Mark Winstanley

Andrew Conley

Fritha Hanning

Sarah Holwell

Gary Forgeson

Elizabeth Thompson

Mark Jeffrey

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.

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.

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

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

Associations between biomarkers with survival will be assessed in the future.

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

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.

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.

The intensity of adverse events will be assessed using the NCI Common Terminology Criteria for Adverse Events version 4 (NCI CTCAE v4.03)

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.

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.

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.

Delivered dose-intensity of cisplatin, etoposide and bleomycin will be assessed.

Overall survival is measured from the date of randomisation until death from any cause, or the date of last known follow-up alive.

Spots Global Cancer Trial Database for bleomycin (active name: bleomycin sulfate)