Surgery and Combination Chemotherapy in Treating Children With Extracranial Germ Cell Tumors

OBJECTIVES:

I. Determine whether children with newly diagnosed low- or intermediate-risk extracranial
germ cell tumors (GCTs) can maintain a 3-year event-free survival of at least 92% (for
intermediate-risk tumors only) and overall survival of at least 95% (both low-risk and
intermediate-risk tumors) after treatment with surgery followed by compressed cisplatin,
etoposide, and bleomycin (low-risk disease closed to accrual as of 01/20/10).

II. Determine the percentage of patients with stage I ovarian or stage I testicular GCTs for
whom chemotherapy can be eliminated.

III. Determine the percentage of intermediate-risk patients who require only 3 courses of
therapy.

IV. Determine the acute toxic effects of compressed therapy in these patients. V. Determine
the long-term sequelae in patients treated with this regimen. VI. Determine the number of
hospital days and total drug doses required for patients treated with compressed therapy.

VII. Compare the number of protocol-directed treatment days used in CCG-8882 vs the number of
treatment days used in this study.

VIII. Determine the cytogenetic and molecular genetic features in patients treated with this
regimen.

OUTLINE: Patients are stratified according to disease risk (low vs intermediate).

SURGERY: Patients undergo surgical resection.

Low-risk disease: Patients with gonadal primaries and no evidence of disease after surgery
undergo monitoring for disease progression. Patients who remain disease free receive no
further treatment. Patients who have disease progression after surgery receive compressed
induction chemotherapy. (closed to accrual as of 01/20/2010)

Intermediate-risk disease: After surgery, patients proceed to compressed induction
chemotherapy.

COMPRESSED INDUCTION CHEMOTHERAPY: Patients receive cisplatin IV over 90 minutes and
etoposide IV over 90 minutes on days 1-3 and bleomycin IV over ≥ 10 minutes on day 1.
Treatment repeats every 3 weeks for 3 courses (weeks 0, 3, and 6).

After completion of compressed induction chemotherapy, patients who have no change in disease
status or disease progression are removed from study. Patients with no evidence of disease
receive no further therapy. Patients with a partial response or who have abnormal tumor
markers proceed to second-look surgery and/or 3 more courses of compressed consolidation
chemotherapy.

SECOND-LOOK SURGERY: Patients undergo surgical resection of residual tumor. After surgery,
patients who are in pathologic complete response and have normal tumor markers receive no
further therapy. Patients who remain with a partial response after surgery receive compressed
consolidation chemotherapy.

COMPRESSED CONSOLIDATION CHEMOTHERAPY: Patients receive cisplatin, etoposide, and bleomycin
as in induction chemotherapy in weeks 10, 13, and 16.

Patients are followed up monthly for 6 months, every 3 months for 18 months, and then
annually for up to 10 years.

Inclusion Criteria:

- Extracranial germ cell tumor that contains 1 of the following malignant histologies:
NOTE: Mixed germ cell tumors that include mature/immature teratoma are eligible
provided 1 of the 3 histologies listed above is also present in the tumor.

- Yolk sac tumor

- Embryonal carcinoma

- Choriocarcinoma

- Low-risk disease (closed to accrual as of 01/20/10)

- Stage I gonadal tumors (ovarian and testicular)

- Must have undergone complete surgical and radiologic staging to exclude the
possibility of > stage I disease

- Intermediate-risk disease

- Stage II, III, or IV malignant testicular GCT

- Stage II or III malignant ovarian GCT

- Stage I or II malignant extragonadal GCT

- Previously stage I gonadal patients who have relapsed on the low-risk
(observation) stratum of this study(closed to accrual as of 01/20/10)

- Patients with immature teratoma or mature teratoma who relapse with a malignant
component

- No patients with any of the following diagnoses:

- Stage IV ovarian and stage III-IV extragonadal GCT

- Intracranial GCT

- Pure mature or immature teratoma, pure dysgerminoma, or seminoma

- Patients with a non-germ cell component in their GCT (e.g., primitive
neuroectodermal tumors or rhabdomyosarcoma)

- Alpha-fetoprotein and beta human chorionic gonadotropin tumor markers known

- If > 5 days have elapsed from the time of obtaining original markers, tumor
markers must be repeated before enrollment of low-risk patients and before
initiating therapy in intermediate-risk patients (the results of the repeated
tumor markers do not have to be known at the time of study enrollment)

- Must be enrolled within 6 weeks of original diagnostic surgery

- Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR a serum creatinine based on
age/gender as follows:

- ≤ 0.4 mg/dL (for patients 1 to 5 months of age)

- ≤ 0.5 mg/dL (for patients 6 to 11 months of age)

- ≤ 0.6 mg/dL (for patients 1 year of age)

- ≤ 0.8 mg/dL (for patients 2 to 5 years of age)

- ≤ 1.0 mg/dL (for patients 6 to 9 years of age)

- ≤ 1.2 mg/dL (for patients 10 to 12 years of age)

- ≤ 1.4 mg/dL (for female patients ≥ 13 years of age)

- ≤ 1.5 mg/dL (for male patients 13 to 15 years of age)

- ≤ 1.7 mg/dL (for male patients ≥ 16 years of age)

- No prior chemotherapy

- No prior radiotherapy