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

NCT02582697 | Recruiting Phase 3 DMC

• 2 other identifiers: ANZUP1302ACTRN12613000496718
• Study Type: interventional
• Target: 500
• Locations: 3 countries
• Sites: 28

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.

Conditions

Germ Cell Tumor

Keywords

Germ Cell; Intermediate and poor-risk metastatic germ cell tumours

Outcome Measures

Primary Outcomes (1)

• 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

  From randomisation up to disease progression or date of death whichever come first, assessed up to 5 years

Secondary Outcomes (8)

• Initial response assessment

  At end of chemotherapy treatment, treatment planned for 12 weeks

• Final response assessment

  At 6 months

• Adverse events (worst grade according to NCI CTCAE v4.03)

  From start of chemotherapy until 30 days after last dose, an average of 4 months

• Health-related quality of life

  From date of randomisation until date of 18 month follow-up

• Health-related quality of life for testicular cancer

  From date of randomisation until date of 18 month follow-up

Other Outcomes (1)

• Exploratory biomarker investigations

  Baseline

Study Arms (2)

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.

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.

Drug: Bleomycin (active name: Bleomycin Sulfate); Drug: Etoposide; Drug: Cisplatin; Drug: Pegylated G-CSF (Pegfilgrastim); Drug: Filgrastim

Interventions

Bleomycin (active name: Bleomycin Sulfate) 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.

Also known as: Blenamax (Aspen), DBL Bleomycin Sulphate (Willow Pharmaceuticals Pty Limited), Bleo Powder for injection (Hospira)

Experimental Arm - Accelerated BEP; Standard Arm - Standard BEP

Etoposide 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.

Also known as: DBL Etoposide Injection (Hospira), Etopophos (Bristol-Myers Squibb), Etoposide (Pfizer), Etoposide Ebewe (Sandoz)

Experimental Arm - Accelerated BEP; Standard Arm - Standard BEP

Cisplatin 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.

Also known as: Cisplatin Ebewe (Sandoz), Cisplatin injection (Pfizer), DBL Cisplatin Injection (Hospira)

Experimental Arm - Accelerated BEP; Standard Arm - Standard BEP

Pegylated G-CSF (Pegfilgrastim) 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.

Also known as: Neulasta Syringe with Automatic Needle Guard (Amgen)

Experimental Arm - Accelerated BEP; Standard Arm - Standard BEP

Filgrastim 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.

Also known as: Neupogen (Amgen), Nivestim (Hospira), Tevagrastim (Teva Pharma Australia Pty Ltd), Zarzio (Sandoz)

Experimental Arm - Accelerated BEP; Standard Arm - Standard BEP

Eligibility Criteria

• Age: 11 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• Adequate bone marrow function with ANC ≥1.0 x 10\^9/L, Platelet count ≥100 x 10\^9/L
• 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

You may not qualify if:

• 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.
• 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
• 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

Sponsors & Collaborators

• University of Sydney: lead
• Australian and New Zealand Urogenital and Prostate Cancer Trials Group: collaborator
• Cambridge University Hospitals NHS Foundation Trust: collaborator
• Cancer Trials Ireland: collaborator
• Children's Oncology Group: collaborator
• Dana-Farber Cancer Institute: collaborator
• University of Southern California: collaborator

Study Sites (28)

Memorial Sloan Kettering Cancer Centre

New York, New York, 10065, United States

RECRUITING

Calvary Mater Newcastle

Newcastle, New South Wales, 2298, Australia

RECRUITING

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

RECRUITING

Prince of Wales Hospital

Sydney, New South Wales, 2031, Australia

RECRUITING

Chris O'Brien Lifehouse

Sydney, New South Wales, 2050, Australia

RECRUITING

Macquarie Cancer Clinical Trials

Sydney, New South Wales, 2109, Australia

RECRUITING

Concord Repatriation General Hospital

Sydney, New South Wales, 2139, Australia

RECRUITING

Westmead Hospital

Sydney, New South Wales, 2145, Australia

WITHDRAWN

Nepean Hospital

Sydney, New South Wales, 2751, Australia

RECRUITING

Tweed Hospital

Tweed Heads, New South Wales, 2485, Australia

RECRUITING

SAN Clinical Trials Unit

Wahroonga, New South Wales, 2076, Australia

RECRUITING

Royal Brisbane & Women's Hospital

Brisbane, Queensland, 4029, Australia

RECRUITING

Queensland Children's Hospital

South Brisbane, Queensland, 4101, Australia

RECRUITING

Princess Alexandra

Woolloongabba, Queensland, 4102, Australia

RECRUITING

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

RECRUITING

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

ACTIVE NOT RECRUITING

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

RECRUITING

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

RECRUITING

Peter MacCallum Cancer Centre

East Melbourne, Victoria, 3002, Australia

RECRUITING

Austin Health

Heidelberg, Victoria, 3084, Australia

RECRUITING

Sunshine Hospital

St Albans, Victoria, 3021, Australia

WITHDRAWN

Border Medical Oncology

Wodonga, Victoria, 3690, Australia

RECRUITING

Fiona Stanley Hospital

Murdoch, Western Australia, 6847, Australia

RECRUITING

Starship Children's Hospital

Grafton, Auckland, 1023, New Zealand

RECRUITING

Auckland Hospital

Grafton, Auckland, 1142, New Zealand

RECRUITING

Palmerston North Hospital

Roslyn, Palmerston North, 4442, New Zealand

RECRUITING

Christchurch Hospital

Christchurch, 8011, New Zealand

RECRUITING

Dunedin Hospital

Dunedin, 9054, New Zealand

WITHDRAWN

Related Publications (1)

• 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.

  PMID: 30157803 DERIVED

MeSH Terms

Conditions

Neoplasms, Germ Cell and Embryonal

Interventions

Bleomycin; Injections; Etoposide; etoposide phosphate; Cisplatin; pegfilgrastim; Filgrastim

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Drug Administration Routes; Drug Therapy; Therapeutics; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Proteins; Biological Factors

Study Officials

• Peter Grimison

  Chris O'Brien Lifehouse

  STUDY CHAIR

Central Study Contacts

P3BEP Trial Coordinator

CONTACT

+6195625000; p3bep@ctc.usyd.edu.au

P3BEP Project Manager

CONTACT

+6195625000; p3bep@ctc.usyd.edu.au

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2015
• First Posted: October 21, 2015
• Study Start: February 1, 2014
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: June 15, 2025

Record last verified: 2025-06

Locations

AU (22); US (1); NZ (5)