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Clinical Correlative Studies In Primary Central Nervous System Germ Cell Tumors: The Third International CNS Germ Cell Tumor Study Group Protocol


Phase 2
N/A
N/A
Open (Enrolling)
Both
Brain and Central Nervous System Tumors

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Trial Information

Clinical Correlative Studies In Primary Central Nervous System Germ Cell Tumors: The Third International CNS Germ Cell Tumor Study Group Protocol


OBJECTIVES:

- Determine the two-year event-free survival of patients with primary CNS germ cell
tumors treated with carboplatin, etoposide, cyclophosphamide, and filgrastim (G-CSF)
with or without radiotherapy and/or high-dose chemotherapy with autologous bone marrow
or peripheral blood stem cell transplantation.

- Determine the prognostic significance of slow-responding tumor marker normalization in
patients treated with this regimen.

- Determine the prognostic significance of syncytiotrophoblastic giant cell component and
cerebrospinal fluid beta-human chorionic gonadotropin elevation in patients treated
with this regimen.

- Assess the early and late endocrinologic, neuropsychometric, and quality of life
sequelae in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to risk status (low
vs intermediate or high).

Regimen A (Low-risk patients)

- Chemotherapy: Patients receive carboplatin IV over 4 hours and etoposide IV over 2
hours on days 1-2 and filgrastim (G-CSF) subcutaneously (SC) once daily beginning on
day 3 and continuing until blood counts recover (course 1). Patients also receive
cyclophosphamide IV over 1 hour and etoposide IV over 2 hours on days 22 and 23 and
G-CSF SC once daily beginning on day 24 and continuing until blood counts recover
(course 2).

- Patients with complete response (CR) to initial chemotherapy receive 2 additional
courses of chemotherapy as above and then proceed to observational phase. Patients with
partial response (PR) to initial chemotherapy receive 2 additional courses of
chemotherapy as above.

- Patients with CR after additional chemotherapy receive another 2 additional courses of
chemotherapy as above and then proceed to observational phase. Patients with PR after
additional chemotherapy undergo biopsy and/or resection of residual tumor.

- Patients with evidence of malignant germ cell tumor (GCT) on resection undergo
radiotherapy. Patients with no evidence of malignant GCT on resection but with scar,
fibrosis, or mature teratoma receive 2 additional courses of chemotherapy as above and
then proceed to observational phase. Patients with no evidence of malignant GCT on
resection but with immature teratoma receive carboplatin IV over 4 hours,
cyclophosphamide IV over 1 hour, and etoposide IV over 2 hours on days 1-2 and 22-23.
Patients who underwent complete resection of residual tumor proceed to observational
phase. Patients who underwent a biopsy only or an incomplete resection of residual
tumor undergo radiotherapy.

Regimen B (Intermediate and high-risk patients)

- Patients receive carboplatin IV over 4 hours, cyclophosphamide IV over 1 hour, and
etoposide IV over 2 hours on days 0-1. Patients also receive G-CSF SC once daily
beginning on day 2 and continuing until blood counts recover. Treatment repeats every
21 days for a total of 2 courses. Patients undergo bone marrow or peripheral blood stem
cell harvest prior to second course of chemotherapy.

- Patients with rapid CR to 2 initial courses of chemotherapy receive an additional 2
courses of chemotherapy as above and then proceed to observational phase. Patients with
a PR or slow response to 2 initial courses of chemotherapy receive 2 additional courses
of chemotherapy as above. Patients with a CR to courses 3 and 4 receive 2 more courses
of chemotherapy and then proceed to observational phase. Patients with a PR to courses
3 and 4 undergo a biopsy and/or resection of residual tumor.

- Patients with no evidence of malignant GCT on resection but with scar, fibrosis, or
mature teratoma receive carboplatin IV over 4 hours and etoposide IV over 2 hours on
days 1 and 2 and cyclophosphamide IV over 1 hour and etoposide IV over 2 hours on days
22 and 23 and proceed to observational phase. Patients with teratoma on resection
receive additional treatment as in regimen A. Patients with evidence of pure germinoma
on resection undergo radiotherapy.

- Patients with evidence of other malignant GCT on resection undergo high-dose
chemotherapy (HDCx) with bone marrow or peripheral blood stem cell support (PBSCS)
comprising thiotepa IV over 3 hours and etoposide IV over 1 hour on days -8 through -6;
carboplatin IV over 4 hours on days -5 through -3; reinfusion of autologous bone marrow
or peripheral blood stem cells on day 0; and G-CSF SC or IV every 12 hours beginning on
day 1 and continuing until blood counts recover. Patients then undergo radiotherapy.

Quality of life is assessed before bone marrow or PBSCS and then every 2 years thereafter.

Patients are followed at day 42, at 3 months, then every 3 months for 1 year, every 4 months
for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 80 patients (40 per stratum) will be accrued for this study
within 4 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed newly diagnosed primary CNS germ cell tumor OR

- Serum or cerebrospinal fluid (CSF) elevation of alpha-fetoprotein (AFP) or beta-human
chorionic gonadotropin (beta-HCG) greater than 50 ng/mL

- Low-risk disease:

- Histologically proven pure germinoma

- Localized, nonmetastatic disease

- Normal CSF

- Normal serum tumor markers

- Intermediate-risk disease:

- Histologically proven germinoma

- Beta-HCG-positive syncytiotrophoblastic giant cell component AND/OR

- CSF elevation of beta-HCG to less than 50 ng/mL

- High-risk disease:

- Histologically proven choriocarcinoma, endodermal sinus tumor, or embryonal
carcinoma

- Elevated serum and/or CSF AFP OR

- Elevated serum beta-HCG OR

- Elevated CSF beta-HCG greater than 50 ng/mL OR

- Disseminated disease by MRI and/or CSF cytology

PATIENT CHARACTERISTICS:

Age:

- Any age

Performance status:

- Not specified

Life expectancy:

- Not specified

Hematopoietic:

- Not specified

Hepatic:

- Bilirubin less than 2.0 mg/dL

- Indirect hyperbilirubinemia due to Gilbert's syndrome is allowed

- AST and ALT less than 5 times upper limit of normal

Renal:

- Creatinine clearance greater than 60 mL/min

Cardiovascular:

- Cardiac function normal by echocardiogram

- No myocardial infarction or ischemia in patients over 30 years

- Fractional shortening greater than 30%

Other:

- No unacceptable morbidity of organ systems outside the CNS

- Not pregnant

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- No prior chemotherapy

Endocrine therapy:

- No concurrent corticosteroids administered solely for antiemesis during study
chemotherapy

Radiotherapy:

- No prior cranial radiotherapy

Surgery:

- Not specified

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Jonathan L. Finlay, MB, ChB

Investigator Role:

Study Chair

Investigator Affiliation:

Children's Hospital Los Angeles

Authority:

United States: Federal Government

Study ID:

CDR0000068950

NCT ID:

NCT00025324

Start Date:

December 2000

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • childhood central nervous system germ cell tumor
  • adult central nervous system germ cell tumor
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms
  • Neoplasms, Germ Cell and Embryonal

Name

Location

Children's Hospital Los AngelesLos Angeles, California  90027-0700
Children's Hospital of the King's DaughtersNorfolk, Virginia  23507