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.
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
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.
Significant cardiac disease resulting in inability to tolerate IV fluid hydration for cisplatin
Significant co-morbid respiratory disease that contraindicates the use of bleomycin
Parallel
Bleomycin (active name: Bleomycin Sulfate)
DrugStandard 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
DrugStandard 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
DrugStandard 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)
DrugStandard 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
DrugStandard 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.
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
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.
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.
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)
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.
Exploratory biomarker investigations
Associations between biomarkers with survival will be assessed in the future.
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University of Sydney
Lead sponsor
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
