Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Objectives

1. 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).
2. Determine the percentage of patients with stage I ovarian or stage I testicular GCTs for whom chemotherapy can be eliminated.
3. Determine the percentage of intermediate-risk patients who require only 3 courses of therapy.
4. Determine the acute toxic effects of compressed therapy in these patients.
5. Determine the long-term sequelae in patients treated with this regimen.
6. Determine the number of hospital days and total drug doses required for patients treated with compressed therapy.
7. Compare the number of protocol-directed treatment days used in CCG-8882 vs the number of treatment days used in this study.
8. Determine the cytogenetic and molecular genetic features in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Extracranial germ cell tumor that contains 1 of the following malignant histologies:
  • Yolk sac tumor
  • Embryonal carcinoma
  • Choriocarcinoma
   [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.]

• 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

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy

Surgery

• See Disease Characteristics

Patient Characteristics:

Age

• 21 and under at diagnosis (under 15 for patients with primary testicular tumors; if over 15, will be treated as adults)

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• 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)

Expected Enrollment

A total of 306 patients (126 with low-risk disease and 180 with intermediate-risk disease) will be accrued for this study within 6 years.

Outcomes

Event-free survival

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 therapy: 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.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

A. Lindsay Frazier, MD, ScM, Protocol chair		Ph: 617-632-2273; 866-790-4500

Registry Information
Official Title		A Phase III Study Of Reduced Therapy In The Treatment Of Children With Low And Intermediate Risk Extracranial Germ Cell Tumors
Trial Start Date		2003-11-03
Trial Completion Date		2010-10-18 (estimated)
Registered in ClinicalTrials.gov		NCT00053352
Date Submitted to PDQ		2002-12-02
Information Last Verified		2011-08-02
NCI Grant/Contract Number		CA30969

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