NCI ID NCI-2017-00559
NCT ID NCT02582697
Primary Purpose TREATMENT
Anatomic Sites Multiple
Minimum Age 11 Years
Maximum Age 45 Years
Gender BOTH
Lead Org Children's Oncology Group
Principal Investigator Farzana Pashankar
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Accelerated or Standard BEP Chemotherapy in Treating Patients with Intermediate or Poor-Risk Metastatic Germ Cell Tumors

This phase III trial compares the effect of an accelerated schedule of bleomycin sulfate, etoposide phosphate, and cisplatin (BEP) chemotherapy to the standard schedule of BEP chemotherapy for the treatment of patients with intermediate or poor-risk germ cell tumors that have spread to other places in the body (metastatic). Drugs used in chemotherapy, such as bleomycin sulfate, etoposide phosphate, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving BEP chemotherapy on a faster, or “accelerated” schedule may work better with fewer side effects in treating patients with intermediate or poor-risk metastatic germ cell tumors compared to the standard schedule.


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

Participating Clinics

Alliance for Childhood Diseases/Cure 4 the Kids Foundation

One Breakthrough Way
Las Vegas, NV 89135