A Randomized Phase 3 Trial of Accelerated Versus Standard BEP Chemotherapy for Patients with Intermediate and Poor-Risk Germ Cell Tumors
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.
Inclusion Criteria -
•Age ≥ 11 years and ≤ 45 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
•Intermediate or poor prognosis as defined by IGCCC classification3 (modified with different LDH criteria for intermediate risk non-seminoma, and inclusion of ovarian primaries). (See protocol for more information).
•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
Exclusion Criteria -
•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: * 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
Dan Zuckerman, M.D.
NRG (NRG Oncology)
The Pacific Cancer Research Consortium clinical trials are offered at multiple locations throughout Oregon, Washington, Alaska, California, and Idaho. To find a location near you, please contact the Patient Engagement Center at 844-552-2734.