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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
19
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)
Given SQ once daily 5 micrograms/kg/dose Starting on Day 6 (Week 1, 4, 7, 10) Daily until ANC \> 5,000/uL
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)
Feasibility of adding cyclophosphamide to a PEB backbone
Time frame: 2 years
Maximum tolerated dose
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).
Time frame: 21 days
Estimate the response rate
To estimate the response rate in this group of patients to a regimen of cyclophosphamide combined with cisplatin, etoposide, bleomycin (C-PEB).
Time frame: Length of study
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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)
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)
Stage III/IV extragonadal tumors: biopsy followed by a definitive surgical excision after maximal chemotherapy effect, likely after 4 cycles of therapy
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.
Comprehensive Cancer Center at University of Alabama at Birmingham
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Phoenix Children's Hospital
Phoenix, Arizona, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Southern California Permanente Medical Group
Downey, California, United States
Loma Linda University Cancer Institute at Loma Linda University Medical Center
Loma Linda, California, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Children's Hospital Central California
Madera, California, United States
Children's Hospital of Orange County
Orange, California, United States
Kaiser Permanente Medical Center - Oakland
Sacramento, California, United States
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San Diego, California, United States
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