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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00066482




Registration number
NCT00066482
Ethics application status
Date submitted
6/08/2003
Date registered
7/08/2003
Date last updated
17/10/2013

Titles & IDs
Public title
Combination Chemotherapy in Treating Children With Newly Diagnosed Malignant Germ Cell Tumors
Scientific title
Pilot Study of Cisplatin, Etoposide, Bleomycin and Escalating Dose Cyclophosphamide Therapy for Children With High Risk Malignant Germ Cell Tumors
Secondary ID [1] 0 0
CDR0000316244
Secondary ID [2] 0 0
AGCT01P1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Childhood Germ Cell Tumor 0 0
Extragonadal Germ Cell Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Testicular
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - bleomycin sulfate
Treatment: Other - filgrastim
Treatment: Drugs - cisplatin
Treatment: Drugs - cyclophosphamide
Treatment: Drugs - etoposide
Treatment: Surgery - conventional surgery
Treatment: Other - MESNA

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.


Treatment: Other: 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)

Treatment: Other: filgrastim
Given SQ once daily 5 micrograms/kg/dose Starting on Day 6 (Week 1, 4, 7, 10) Daily until ANC \> 5,000/uL

Treatment: Drugs: 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)

Treatment: Drugs: 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)

Treatment: Drugs: 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)

Treatment: Surgery: conventional surgery
Stage III/IV extragonadal tumors: biopsy followed by a definitive surgical excision after maximal chemotherapy effect, likely after 4 cycles of therapy

Treatment: Other: 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.
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Feasibility of adding cyclophosphamide to a PEB backbone
Timepoint [1] 0 0
2 years
Secondary outcome [1] 0 0
Maximum tolerated dose
Timepoint [1] 0 0
21 days
Secondary outcome [2] 0 0
Estimate the response rate
Timepoint [2] 0 0
Length of study

Eligibility
Key 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
Minimum age
No limit
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2004
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
19
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
6001 - Perth
Recruitment outside Australia
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Alabama
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Delaware
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District of Columbia
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Florida
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Georgia
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Indiana
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Kentucky
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Maine
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Mississippi
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Missouri
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North Carolina
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Ohio
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Oklahoma
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Pennsylvania
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South Carolina
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Tennessee
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Texas
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West Virginia
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British Columbia
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Newfoundland and Labrador
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Quebec
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Saskatchewan
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Santurce

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00066482
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Marcio A. Malogolowkin, MD
Address 0 0
Children's Hospital Los Angeles
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
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Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00066482