Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors

Inclusion Criteria:

• Histologically confirmed (at original diagnosis) extracranial germ cell tumor (GCT) containing 1 of the following malignant elements:

  • Yolk sac tumor (endodermal sinus tumor)
  • Choriocarcinoma
  • Embryonal carcinoma

• Meets 1 of the following disease criteria:

  • Recurrent malignant disease
  • Chemotherapy-resistant disease
  • Relapsed disease
  • Disease refractory to conventional therapy
• Measurable disease
• Must have received a prior first-line chemotherapy regimen that included cisplatin
• Patients with tumor marker (AFP and/or BHCG) elevation alone or bone scan findings alone are not eligible*
• Patients with immature teratoma (any grade), germinoma, sex-cord stromal tumors, or recurrent GCT previously treated with surgery alone are not eligible
• Karnofsky performance status (PS) 50-100% (age > 16 years) OR Lansky PS 50-100% (age ≤ 16 years) OR ECOG PS 0-2
• Life expectancy ≥ 8 weeks
• Absolute neutrophil count ≥ 750/mm³
• Platelet count ≥ 75,000/mm³ (transfusion independent)

• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine normal based on age/gender, as defined by the following:

  • ≤ 0.4 mg/dL (1 month to < 6 months of age)
  • ≤ 0.5 mg/dL (6 months to < 1 year of age)
  • ≤ 0.6 mg/dL (1 to < 2 years of age)
  • ≤ 0.8 mg/dL (2 to < 6 years of age)
  • ≤ 1.0 mg/dL (6 to < 10 years of age)
  • ≤ 1.2 mg/dL (10 to < 13 years of age)
  • ≤ 1.4 mg/dL (13 to ≥ 16 years of age) (female)
  • ≤ 1.5 mg/dL (13 to < 16 years of age) (male)
  • ≤ 1.7 mg/dL (≥ 16 years of age) (male)
• Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
• ALT < 2.5 times ULN for age
• Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by gated radionuclide study
• No dyspnea at rest
• No exercise intolerance
• Pulse oximetry > 94% (if there is clinical indication for determination)
• Patients with seizure disorder are eligible provided they are on non-enzyme inducing anticonvulsants and seizures are well controlled
• No CNS toxicity > grade 2
• No active graft-versus-host disease
• No allergy to Cremophor EL or castor oil
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other concurrent chemotherapy or immunomodulating agents
• Recovered from prior chemotherapy, immunotherapy, or radiotherapy
• At least 1 week since prior growth factors (2 weeks for pegfilgrastim)
• At least 1 week since prior biologic therapy
• At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosourea)
• At least 2 weeks since prior local palliative radiotherapy (i.e., small port)
• At least 6 months since prior craniospinal radiotherapy or radiotherapy to ≥ 50% of pelvis
• At least 6 weeks since other prior substantial bone marrow radiotherapy
• At least 6 months since prior allogeneic stem cell transplantation
• Concurrent radiotherapy to localized painful lesions allowed provided at least 1 measurable lesion is not irradiated