Combination Chemotherapy in Treating Children With Newly Diagnosed Malignant Germ Cell Tumors
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Purpose
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 | Intervention |
|---|---|
|
Childhood Germ Cell Tumor Extragonadal Germ Cell Tumor |
Biological: bleomycin sulfate Biological: filgrastim Drug: cisplatin Drug: cyclophosphamide Drug: etoposide Procedure: conventional surgery Biological: MESNA |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Pilot Study of Cisplatin, Etoposide, Bleomycin and Escalating Dose Cyclophosphamide Therapy for Children With High Risk Malignant Germ Cell Tumors |
- Event Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Maximum tolerated dose [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]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 ] [ Designated as safety issue: No ]To estimate the response rate in this group of patients to a regimen of cyclophosphamide combined with cisplatin, etoposide, bleomycin (C-PEB).
| Enrollment: | 19 |
| Study Start Date: | July 2004 |
| Primary Completion Date: | August 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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)
Other Names:
Biological: filgrastim
Given SQ once daily 5 micrograms/kg/dose Starting on Day 6 (Week 1, 4, 7, 10) Daily until ANC > 5,000/uL
Other Names:
Drug: cisplatin
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)
Other Names:
Drug: cyclophosphamide
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)
Other Names:
Drug: etoposide
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)
Other Names:
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
Biological: MESNA
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.
Other Names:
|
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.
Eligibility| Ages Eligible for Study: | up to 21 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Show 98 Study Locations| Study Chair: | Marcio A. Malogolowkin, MD | Children's Hospital Los Angeles |
More Information
Additional Information:
No publications provided
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00066482 History of Changes |
| Other Study ID Numbers: | AGCT01P1, CDR0000316244 |
| Study First Received: | August 6, 2003 |
| Last Updated: | March 12, 2013 |
| Health Authority: | United States: Federal Government |
Keywords provided by Children's Oncology Group:
|
childhood teratoma childhood extragonadal germ cell tumor |
Additional relevant MeSH terms:
|
Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Mesna Bleomycin Etoposide phosphate Cisplatin Cyclophosphamide Etoposide Lenograstim Protective Agents Physiological Effects of Drugs Pharmacologic Actions |
Antibiotics, Antineoplastic Antineoplastic Agents Therapeutic Uses Radiation-Sensitizing Agents Immunosuppressive Agents Immunologic Factors Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Myeloablative Agonists Antineoplastic Agents, Phytogenic Adjuvants, Immunologic |
ClinicalTrials.gov processed this record on June 18, 2013