Combination Chemotherapy in Treating Children With Newly Diagnosed Malignant Germ Cell Tumors
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|ClinicalTrials.gov Identifier: NCT00066482|
Recruitment Status : Completed
First Posted : August 7, 2003
Last Update Posted : October 17, 2013
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.
|Condition or disease||Intervention/treatment||Phase|
|Childhood Germ Cell Tumor Extragonadal Germ Cell Tumor||Biological: bleomycin sulfate Biological: filgrastim Drug: cisplatin Drug: cyclophosphamide Drug: etoposide Procedure: conventional surgery Biological: MESNA||Not Applicable|
- 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 (Clinical Trial)|
|Actual Enrollment :||19 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Study of Cisplatin, Etoposide, Bleomycin and Escalating Dose Cyclophosphamide Therapy for Children With High Risk Malignant Germ Cell Tumors|
|Study Start Date :||July 2004|
|Actual Primary Completion Date :||April 2007|
Experimental: combination chemotherapy
Induction therapy: bleomycin sulfate 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. MESNA & 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. 6 patients receive escalating doses of cyclophosphamide until the maximum tolerated dose (MTD) is determined.
Evaluated after 4 courses of therapy. Partial response or stable disease undergo second-look conventional surgery & receive 2 more courses of induction therapy then re-evaluated. Those who do not achieve complete response (CR) after a total of 6 courses may undergo a third conventional surgery. Tumor that cannot be removed are removed from study therapy. Achievement of a CR at anytime are followed monthly for 1 year, every 6 months for 1 year, and then annually for 3 years.
Biological: bleomycin 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)
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)
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)
Procedure: conventional surgery
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.
- Feasibility of adding cyclophosphamide to a PEB backbone [ Time Frame: 2 years ]
- Maximum tolerated dose [ Time Frame: 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 [ Time Frame: 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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00066482
|Study Chair:||Marcio A. Malogolowkin, MD||Children's Hospital Los Angeles|