nct02582697

Eligibility

Inclusion Criterea

• Histologically or cytologically confirmed germ cell tumor (non-seminoma or seminoma); or exceptionally raised tumor markers (alpha-fetoprotein [AFP] >= 1000 ng/mL and/or human chorionic gonadotropin [HCG] >= 5000 IU/L) without histologic or cytologic confirmation in the rare case where pattern of metastases consistent with germ cell tumor (GCT), high tumor 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 International Germ Cell Cancer Consensus Classification (IGCCC) classification (modified with different lactate dehydrogenase [LDH] criteria for intermediate risk non-seminoma, and inclusion of ovarian primaries); see below * Primary site: Testis or retro-peritoneum or mediastinum ** Histology: Non-seminoma *** Prognostic category: Intermediate **** Clinical Factors: Testes/retroperitoneal primary and no liver, bone, brain or other non-pulmonary visceral metastases and intermediate markers – any of: ***** AFP >= 1000 ng/mL and =< 10 000 ng/mL ***** HCG >= 5000 IU/L and =< 50 000 IU/L ***** LDH >= 3.0 x upper limit of normal (ULN) and =< 10 x ULN *** Prognostic category: Poor **** Clinical Factors: Mediastinal primary or liver, bone, brain or other non-pulmonary visceral metastases or poor markers – any of: ***** AFP > 10 000 ng/mL or ***** HCG > 50 000 IU/L or ***** LDH > 10 x ULN ** Histology: Seminoma *** Prognostic category: Intermediate **** Clinical factors: Any primary site and liver, bone, brain or other non-pulmonary visceral metastases and normal AFP, any HCG, any LDH * Primary site: Ovary ** Histology: Malignant germ cell tumour histology (any of yolk sac, choriocarcinoma, embryonal carcinoma, mixed malignant GCT) *** Prognostic category: Federation of Gynecology and Obstetrics (FIGO)/Children's Oncology Group (COG) stage IV **** Distant metastases involving liver/spleen parenchyma and/or extra-abdominal organs (including but not limited to inguinal lymph nodes and lymph nodes outside abdominal cavity, lungs, bone, brain) and/or pleural effusion with positive cytology
• Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
• Platelet count >= 100 x 10^9/L
• Bilirubin must be =< 1.5 x ULN, except participants with Gilbert’s syndrome where bilirubin must be =< 2.0 x ULN
• Alanine aminotransferase (ALT) and aspartate aminotransferase (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
• 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 glomerular filtration rate (GFR) should be formally measured, e.g. with edetic acid (EDTA) scan
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2, or 3
• Study treatment both planned and able to start within 14 days of randomization
• 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 Criterea

• Other primary malignancy (EXCEPT adequately treated non-melanomatous carcinoma of the skin, germ cell tumor, or other malignancy treated at least 5 years previously with no evidence of recurrence)
• Previous chemotherapy or radiotherapy, except: * Pure seminoma relapsing after adjuvant radiotherapy or adjuvant chemotherapy with 1-2 doses of single agent carboplatin * Non-seminoma and poor prognosis by IGCCC criteria in the rare case where low-dose induction chemotherapy is given prior to registration because patient is not fit enough to receive protocol chemotherapy (e.g. organ failure, vena cava obstruction, overwhelming burden of disease); acceptable regimens include cisplatin 20 mg/m^2 days 1-2 and etoposide 100 mg/m^2 days 1-2; carboplatin area under curve (AUC) 3 days 1-2 and etoposide 100 mg/m^2 days 1-2; or baby-BOP; patients must meet all other inclusion and exclusion criteria at the time of registration * Participants who need to start therapy urgently prior to completing study-specific baseline investigations may commence study chemotherapy prior to registration and randomization; such patients must be discussed with the coordinating center 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
• Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation; women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration
• 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