Childhood Germ Cell Tumor, Extragonadal Germ Cell Tumor
Conditions
Keywords
childhood teratoma, childhood extragonadal germ cell tumor
Brief summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I trial to study the effect on the body of combining cyclophosphamide with cisplatin, etoposide, and bleomycin in treating children who have newly diagnosed malignant germ cell tumors that are not in the brain and gonads.
Detailed description
OBJECTIVES: * Determine the maximum tolerated dose and toxicity profile of cyclophosphamide in combination with bleomycin, etoposide, and cisplatin in pediatric patients with newly diagnosed high-risk extracranial, extragonadal malignant germ cell tumors. * Determine the response rate in patients treated with this regimen. OUTLINE: This is a pilot, multicenter, dose-escalation study of cyclophosphamide. * Induction therapy: Patients receive bleomycin IV over 10-20 minutes on day 1, etoposide IV over 1 hour and cisplatin IV over 4 hours on days 1-5, and cyclophosphamide IV over 1 hour on day 1. Patients also receive filgrastim (G-CSF) subcutaneously once daily beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 6 patients receive escalating doses of cyclophosphamide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Patients are evaluated after 4 courses of therapy. Patients with partial response or stable disease undergo second-look surgery, receive 2 more courses of induction therapy, and are then re-evaluated. Patients who do not achieve complete response (CR) after a total of 6 courses may undergo a third surgery. Patients who still have tumor that cannot be removed are removed from study therapy. Patients who achieve a CR at anytime are followed. Patients are followed monthly for 1 year, every 6 months for 1 year, and then annually for 3 years. PROJECTED ACCRUAL: A total of 6-18 patients will be accrued for this study within 1.3 years.
Interventions
BIOLOGICALbleomycin sulfate
Given IV over 10 minutes. Children ≥ 12 months: 15 units/m2/dose Children \< 12 months: 0.5 units/kg/dose Day 1 (Week 1, 4, 7, 10)
BIOLOGICALfilgrastim
Given SQ once daily 5 micrograms/kg/dose Starting on Day 6 (Week 1, 4, 7, 10) Daily until ANC \> 5,000/uL
DRUGcisplatin
Children ≥ 12 months: Given IV over one hour Dose: 20 mg/m2/dose Days 1-5 (Week 1,4,7,10) Children \< 12 months: Given IV over 4 hours, 0.67 mg/kg/dose Days 1-5 (Week 1,4,7,10)
DRUGcyclophosphamide
Given IV over 1 hour. Children ≥ 12 months: Level 1: 1.2 g/m2/dose Level 2: 1.8 g/m2/dose Level 3: 2.4 g/m2/dose Children \< 12 months: Level 1: 40 mg/kg/dose Level 2: 60 mg/kg/dose Level 3: 80 mg/kg/dose Day 1 (Week 1, 4, 7, 10)
DRUGetoposide
Given IV over 1 hour. Children ≥ 12 months: 100 mg/m2/dose Children \< 12 months: 3.3 mg/kg/dose Day 1-5 (Week 1, 4, 7, 10)
PROCEDUREconventional surgery
Stage III/IV extragonadal tumors: biopsy followed by a definitive surgical excision after maximal chemotherapy effect, likely after 4 cycles of therapy
BIOLOGICALMESNA
Given IV or oral. The total daily MESNA dose is equal to at least 80% of the daily CPM dose. The oral dose of MESNA is 2x the IV dose. Day 1 (Week 1,4,7,10) To be given with CPM.
Sponsors
National Cancer Institute (NCI)
Children's Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed newly diagnosed extracranial germ cell tumors, including 1 of the following types: * Yolk sac carcinoma (endodermal sinus tumor) * Embryonal carcinoma * Choriocarcinoma * Teratoma with mixed malignant elements (malignant teratoma) * High-risk disease, defined as stage III or IV extragonadal germ cell tumors * Must be enrolled on study within 21 days of diagnostic surgical procedure PATIENT CHARACTERISTICS: Age * 21 and under (at original diagnosis) Performance status * ECOG 0-2 * Karnofsky 50-100% (in patients over 16 years of age) * Lansky 50-100% (in patients 16 years of age and under) Life expectancy * At least 2 months Hematopoietic * Absolute neutrophil count at least 1,000/mm\^3 * Platelet count at least 100,000/mm\^3 (transfusion independent) * Hemoglobin at least 10.0 g/dL (transfusion allowed) Hepatic * Not specified Renal * Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min OR * Creatinine based on age as follows: * No greater than 0.8 mg/dL (5 years and under) * No greater than 1.0 mg/dL (6-10 years) * No greater than 1.2 mg/dL (11-15 years) * No greater than 1.5 mg/dL (over 15 years) Pulmonary * FEV\_1/FVC greater than 60% OR * Children who are uncooperative must meet all of the following criteria: * No dyspnea at rest * No exercise intolerance * Pulse oximetry greater than 94% Other * Not pregnant or nursing * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * No prior chemotherapy Endocrine therapy * Not specified Radiotherapy * No prior radiotherapy Surgery * See Disease Characteristics
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Feasibility of adding cyclophosphamide to a PEB backbone | 2 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose | 21 days | Maximum tolerated dose (MTD) and toxicity profile of cyclophosphamide combined with cisplatin, etoposide, bleomycin (C-PEB) in previously untreated children with high-risk malignant germ cell tumors (MGCT). |
| Estimate the response rate | Length of study | To estimate the response rate in this group of patients to a regimen of cyclophosphamide combined with cisplatin, etoposide, bleomycin (C-PEB). |
Countries
Australia, Canada, Puerto Rico, United States
Outcome results
None listed