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