P3BEP: Is an accelerated two-week treatment with BEP chemotherapy as effective as receiving the standard three-week cycle, for patients with metastatic germ cell tumours?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

Exclusion

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)

2. 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.

   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

The above inclusion and exclusion criteria will apply to stage 1 (n=150) and stage 2 (n=500 including stage 1) of the study. All sites will participate in both stages of the study with the exception of the Children's Oncology Group who will be participate in stage 1 only.