Clinical Research Trials

Key Trial Criteria

• Key Inclusion Criteria

  For a patient to be eligible for participation in this study, all of the following criteria must apply.

  • Low risk stratum (stage I ovarian immature teratoma and stage I malignant GCT [all sites]): Patients must be < 50 years of age at enrollment
  • Standard risk 1: Patient must be < 11 years of age at enrollment
  • Standard risk 2: Patients must be >= 11 and < 25 years of age at enrollment
  • Newly diagnosed patients must have histologic verification of a primary extracranial germ cell tumor in any of the categories outlined; elevation of serum tumor markers without histologic confirmation is not sufficient for entry on the trial
    • NOTE: for low risk patients, materials for rapid surgical central review must be sent within 7 days of study enrollment
  • Low risk stage I immature teratoma (IT); site: ovarian; stage: Children's Oncology Group (COG) stage I, Federation of Gynecology and Obstetrics (FIGO) stage IA and IB; grade: 2 or 3; histology: pure immature teratoma (may contain =< 5% of microscopic yolk sac tumor), mixed immature and mature teratoma, (no pathological evidence of mediastinal germ cell tumor [MGCT]); tumor markers: alpha-FP =< 1,000 ng/mL, beta-HCG institutional normal; age (years) < 50
  • Low risk stage I MCGT; site: ovarian, testicular, or extragonadal; stage: COG stage I, FIGO stage IA and IB, American Joint Committee on Cancer (AJCC) testicular stage IA, IB and IS; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed); age (years) < 50
  • Standard risk 1 (SR1); site: ovarian, testicular, or extragonadal; stage: COG stage II-IV, FIGO stage IC, FIGO stage II-IV; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed); age (years) < 11
  • Standard risk 2 (SR2)
    • Site: ovarian; stage: COG stage II and III, FIGO stage IC, II and III; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed); age (years) >= 11 and < 25
    • Site: testicular; stage: COG stage II-IV, AJCC stage II, III, International Germ Cell Consensus Classification (IGCCC) good risk; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed); tumor markers: must be IGCCC good risk; post op: alpha-FP < 1,000 ng/mL, beta-HCG < 5,000 IU/mL and lactate dehydrogenase (LDH) < 3.0 x normal; age (years) >= 11 and < 25
    • Site: extragonadal; stage: COG stage II; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed) age (years) >= 11 and < 25
  • Notes:
    • IGCCC criteria only apply to SR2 patients with a testicular primary tumor
    • Use post-op tumor marker levels to determine IGCCC risk group
    • For the low risk stage I MGCT and the standard risk arms, components of yolk sac tumor, embryonal carcinoma, or choriocarcinoma can be mixed with other forms of GCT, such as seminoma or mature or immature teratoma; if yolk sac tumor is the only malignant component present, then it must be deemed by the pathologist to be greater than a ?microscopic component? of yolk sac tumor (i.e. > 5%)
  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, 2 or 3; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
  • Organ function requirements apply ONLY to patients who will receive chemotherapy (SR1 and SR2 patients)
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2
  • A serum creatinine based on age/gender as follows: (mg/dL)
    • 1 month to < 6 months male: 0.4 female: 0.4
    • 6 months to < 1 year male: 0.5 female: 0.5
    • 1 to < 2 years male: 0.6 female: 0.6
    • 2 to < 6 years male: 0.8 female: 0.8
    • 6 to < 10 years male: 1 female: 1
    • 10 to < 13 years male: 1.2 female: 1.2
    • 13 to < 16 years: male: 1.5 female: 1.4
    • >= 16 years male: 1.7 female: 1.4
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN) for age (for the purpose of this study, the ULN for SGPT is 45 U/L)
  • No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication or determination; pulmonary function tests (PFTs) are not required
  • Eligibility criteria to participate in the pilot study of the AYA-Hears instrument (patient reported outcomes [PROs] of ototoxicity) Note: participants in group 1 will not receive AGCT1531 protocol-directed therapy; all other AYA-HEARS patients must be enrolled on the AGCT1531 SR2 arm in order to participate
  • >= 11 and < 25 years old at enrollment
  • Able to fluently speak and read English
  • Has received prior cisplatin- or carboplatin-based chemotherapy regimen for malignancy including diagnoses other than germ cell tumor
  • Followed for cancer or survivorship care at one of the following institutions:
    • Dana Farber/Harvard Cancer Center
    • Hospital for Sick Children
    • Children's Hospital of Eastern Ontario
    • Oregon Health and Science University
    • Seattle Children's Hospital
    • Yale University
  • Has experienced prior or ongoing hearing impairment due to chemotherapy or radiotherapy as defined by one of the following:
    • Society of Pediatric Oncology (SIOP) grade 1 hearing loss
    • Subjective (patient-reported) hearing difficulties
    • Subjective (patient-reported) tinnitus

• Key Exclusion Criteria

  A patient will not be eligible for participation in this study if any of the following criteria apply.

  • Patients with any diagnoses not listed including:
    • Stage I testicular cancer patients who have undergone primary RPLND (retroperitoneal lymph node dissection)
    • Pure dysgerminoma and pure seminoma
    • Pure mature teratoma
    • Pure immature teratoma COG stage I, grade I
    • Pure immature teratoma COG stage I, grade 2,3 with alpha-fetoprotein (AFP) >= 1000 ng/mL
    • Pure immature teratoma COG stage II - IV or FIGO stage IC to IV
    • "Poor risk" GCT (age >= 11 years old and COG stage IV ovarian, COG stage III or IV EG, or IGCCC intermediate or poor risk testicular), or
    • Primary central nervous system (CNS) germ cell tumor
  • Patients must have had no prior systemic therapy
  • Patients must have had no prior radiation therapy with the exception of CNS irradiation of brain metastases; (this exception only applies to SR1 patients; any patients over age 11 with distant metastases to brain [stage IV disease] would be considered poor risk and therefore not eligible for this trial)
  • Patients with significant respiratory compromise due to either abdominal tumor limiting diaphragmatic excursion or pulmonary metastases should not receive bleomycin and are ineligible for the trial
  • Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential; (this criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2 patients])
  • Lactating females who plan to breastfeed their infants; (this criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2 patients])
  • Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation; (this criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2 patients])