RecruitingPhase 3ACTRN12613000496718

Phase 3 Accelerated BEP Trial: A randomised phase 3 trial of accelerated versus standard BEP chemotherapy for patients with intermediate and poor-risk metastatic germ cell tumours

In patients with intermediate and poor-risk metastatic germ cell tumours is an accelerated BEP chemotherapy regimen as good as, or better than, the standard BEP chemotherapy regimen for response rate.

Sponsor

University of Sydney

Enrollment

500 participants

Start Date

Apr 3, 2014

Study Type

Interventional

Conditions

Intermediate and poor-risk metastatic germ cell tumours (GCTs)

Summary

The purpose of this study is to determine whether accelerated BEP chemotherapy is more effective than standard BEP chemotherapy in males and females with intermediate and poor-risk metastatic germ cell tumours. Who is it for? Male and female participants aged 11 years to 45 years old and you have been diagnosed with metastatic germ cell tumour/s in the testes, ovary, retro-peritoneum or mediastineum and considering first-line chemotherapy. Study details Participants in this study will be randomly (by chance) allocated to one of two groups. Participants in one group will receive the current gold standard treatment for germ cell tumours, which is a chemotherapy combination called BEP (bleomycin, etoposide and cisplatin) administered on a 3 weekly cycle. BEP is given with a drug called pegfilgrastim which encourages white blood cell production and prevents blood cell complications of chemotherapy. Participants in the other group will receive the same dose of BEP but on a 2 weekly schedule. This is called 'accelerated BEP'. Participants will be regularly assessed for treatment response, side effects and quality of life for a period of up to 2 years. This will enable us to determine whether giving the dose of BEP on a 2 weekly schedule is more effective than a 3 weekly schedule. We will also be able to track whether the shorter schedule causes more, the same, or less side effects.

Eligibility

Sex: Both males and femalesMin Age: 11 YearssMax Age: 45 Yearss

Inclusion Criteria12

Age greater than or equal to 11 years and less than or equal to 45 years on the date of randomisation
Histologically or cytologically confirmed germ cell tumour (non-seminoma or seminoma), except in the rare case of exceptionally raised tumour markers (AFP greater than or equal to 1000ng/mL and/or beta-HCG greater than or equal to 5000 IU/L) without histologic or cytologic confirmation 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 modified IGCCC classification (modified with different LDH criteria for intermediate risk non-seminoma, and inclusion of ovarian primaries).
Adequate bone marrow function with ANC greater than or equal to 1.0 x 10^9/L, Platelet count greater than or equal to 100 x 10^9/L
Adequate liver function where bilirubin must be less than or equal to 1.5 x ULN, ALT and AST must be less than or equal to 2.5 x ULN; except if the elevations are due to hepatic metastases, in which case ALT and AST must be less than or equal to 5 x ULN
Adequate renal function of GFR greater than or equal to 60 ml/min. It is recommended that GFR is estimated with the Cockcroft-Gault formula, unless calculated to be less than 60 ml/min or borderline in which case by 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

Exclusion Criteria9

History of a malignancy prior to registration except for germ cell tumour or non-melanomatous carcinoma of the skin
Previous chemotherapy or radiotherapy, except (a)participants with pure seminoma relapsing after radiotherapy or adjuvant chemotherapy with 1-2 doses of single agent carboplatin, (b)participants with NSGCT and poor prognosis by IGCCC criteria receiving pre-protocol chemotherapy (eg. low-dose platinum and etoposide, baby-BOP) , (c)Participants who need to start therapy urgently prior to completing study-specific baseline investigations may commence study chemotherapy prior to registration and randomisation.
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 greater than or equal to grade 2 or clinically significant sensori-neural 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 have been surgically sterilised or use a double barrier method of contraception
Known allergy or hypersensitivity to any of the study drugs
Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse

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Interventions

Patients 16 years or older and randomised to Arm B - Accelerated BEP (Experimental) will receive 4 x 14 day cycles of; Bleomycin 30000 IU IV weekly; Etoposide 100mg/m^2 IV days 1,2,3,4,5; Cisplatin

Patients 16 years or older and randomised to Arm B - Accelerated BEP (Experimental) will receive 4 x 14 day cycles of; Bleomycin 30000 IU IV weekly; Etoposide 100mg/m^2 IV days 1,2,3,4,5; Cisplatin 20mg/m^2 IV days 1,2,3,4,5 and Pegylated G-CSF 6mg SCI on day 6 followed by: 4 doses of Bleomycin 30000IU IV at weekly intervals. Patients less than 16 years old and weighs 45 kgs or more and are randomised to Arm B - Accelerated BEP (Experimental) will receive; Bleomycin 15,000 - 30000 IU IV weekly; Etoposide 100mg/m^2 IV days 1,2,3,4,5; Cisplatin 20mg/m^2 IV days 1,2,3,4,5 and Pegylated G-CSF 6mg SCI on day 6 followed by: 4 doses of Bleomycin 15,000-30000IU IV at weekly intervals. Patients aged less than 16 years and weigh less than 45 kg on day 1 of the treatment cycle and are randomised to Arm B - Accelerated BEP (Experimental) will receive Bleomycin 15,000 - 30000 IU IV weekly; Etoposide 100mg/m^2 IV days 1,2,3,4,5; Cisplatin 20mg/m^2 IV days 1,2,3,4,5 and Filgrastim 10mcg/kg/day until post-nadir absolute neutrophil count is equal to or greater than 1 x 10^9/ L - dose starting day 6 followed by: 4 doses of Bleomycin 15,000-30000IU IV at weekly intervals. For patients less than 16 years old, the exact dose of bleomycin is decided by the treating physician and based on the patients body surface area (BSA) value.