Brain and Central Nervous System TumorsPhase 2NCT00025324
Chemotherapy, Surgery, Radiation Therapy and Bone Marrow or Peripheral Stem Cell Transplantation in Treating Patients With Primary CNS Germ Cell Tumors
A Phase 2 study testing filgrastim, carboplatin and cyclophosphamide in people with Brain and Central Nervous System Tumors, run by Children's Hospital Los Angeles at 4 sites in 3 countries.
Trial summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Brain and Central Nervous System Tumors
- What is being tested?
- filgrastim, carboplatin and cyclophosphamide
- Type of treatment
- Surgery or procedure
- How many people
- Not given
- Where
- 4 sitesin 3 countries
- Study dates
- Dec 2000to not given
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed newly diagnosed primary CNS germ cell tumor OR
- Serum or cerebrospinal fluid (CSF) elevation of alpha-fetoprotein (AFP) or beta-human chorionic gonadotropin (beta-HCG) greater than 50 ng/mL
- Low-risk disease:
- Histologically proven pure germinoma
- Localized, nonmetastatic disease
- Normal CSF
- Normal serum tumor markers
- Intermediate-risk disease:
- Histologically proven germinoma
- Beta-HCG-positive syncytiotrophoblastic giant cell component AND/OR
- CSF elevation of beta-HCG to less than 50 ng/mL
- High-risk disease:
- Histologically proven choriocarcinoma, endodermal sinus tumor, or embryonal carcinoma
- Elevated serum and/or CSF AFP OR
- Elevated serum beta-HCG OR
- Elevated CSF beta-HCG greater than 50 ng/mL OR
- Disseminated disease by MRI and/or CSF cytology
PATIENT CHARACTERISTICS:
Age:
- Any age
Performance status:
- Not specified
Life expectancy:
- Not specified
Hematopoietic:
- Not specified
Hepatic:
- Bilirubin less than 2.0 mg/dL
- Indirect hyperbilirubinemia due to Gilbert's syndrome is allowed
- AST and ALT less than 5 times upper limit of normal
Renal:
- Creatinine clearance greater than 60 mL/min
Cardiovascular:
- Cardiac function normal by echocardiogram
- No myocardial infarction or ischemia in patients over 30 years
- Fractional shortening greater than 30%
Other:
- No unacceptable morbidity of organ systems outside the CNS
- Not pregnant
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- No prior chemotherapy
Endocrine therapy:
- No concurrent corticosteroids administered solely for antiemesis during study chemotherapy
Radiotherapy:
- No prior cranial radiotherapy
Surgery:
- Not specified
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
United States2 sites
Children's Hospital Los Angeles
Los Angeles, California, 90027-0700
Children's Hospital of the King's Daughters
Norfolk, Virginia, 23507
Australia1 site
Princess Margaret Hospital for Children
Perth, Western Australia, 6001
About this study
Official title: Clinical Correlative Studies In Primary Central Nervous System Germ Cell Tumors: The Third International CNS Germ Cell Tumor Study Group Protocol
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells.
PURPOSE: Phase II trial to study the effectiveness of chemotherapy, surgery, radiation therapy, and bone marrow or peripheral stem cell transplantation in treating patients who have primary CNS germ cell tumors.
Read the detailed description
OBJECTIVES:
- Determine the two-year event-free survival of patients with primary CNS germ cell tumors treated with carboplatin, etoposide, cyclophosphamide, and filgrastim (G-CSF) with or without radiotherapy and/or high-dose chemotherapy with autologous bone marrow or peripheral blood stem cell transplantation.
- Determine the prognostic significance of slow-responding tumor marker normalization in patients treated with this regimen.
- Determine the prognostic significance of syncytiotrophoblastic giant cell component and cerebrospinal fluid beta-human chorionic gonadotropin elevation in patients treated with this regimen.
- Assess the early and late endocrinologic, neuropsychometric, and quality of life sequelae in patients treated with this regimen.
OUTLINE: This is a multicenter study. Patients are stratified according to risk status (low vs intermediate or high).
Regimen A (Low-risk patients)
- Chemotherapy: Patients receive carboplatin IV over 4 hours and etoposide IV over 2 hours on days 1-2 and filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 3 and continuing until blood counts recover (course 1). Patients also receive cyclophosphamide IV over 1 hour and etoposide IV over 2 hours on days 22 and 23 and G-CSF SC once daily beginning on day 24 and continuing until blood counts recover (course 2).
- Patients with complete response (CR) to initial chemotherapy receive 2 additional courses of chemotherapy as above and then proceed to observational phase. Patients with partial response (PR) to initial chemotherapy receive 2 additional courses of chemotherapy as above.
- Patients with CR after additional chemotherapy receive another 2 additional courses of chemotherapy as above and then proceed to observational phase. Patients with PR after additional chemotherapy undergo biopsy and/or resection of residual tumor.
- Patients with evidence of malignant germ cell tumor (GCT) on resection undergo radiotherapy. Patients with no evidence of malignant GCT on resection but with scar, fibrosis, or mature teratoma receive 2 additional courses of chemotherapy as above and then proceed to observational phase. Patients with no evidence of malignant GCT on resection but with immature teratoma receive carboplatin IV over 4 hours, cyclophosphamide IV over 1 hour, and etoposide IV over 2 hours on days 1-2 and 22-23. Patients who underwent complete resection of residual tumor proceed to observational phase. Patients who underwent a biopsy only or an incomplete resection of residual tumor undergo radiotherapy.
Regimen B (Intermediate and high-risk patients)
- Patients receive carboplatin IV over 4 hours, cyclophosphamide IV over 1 hour, and etoposide IV over 2 hours on days 0-1. Patients also receive G-CSF SC once daily beginning on day 2 and continuing until blood counts recover. Treatment repeats every 21 days for a total of 2 courses. Patients undergo bone marrow or peripheral blood stem cell harvest prior to second course of chemotherapy.
- Patients with rapid CR to 2 initial courses of chemotherapy receive an additional 2 courses of chemotherapy as above and then proceed to observational phase. Patients with a PR or slow response to 2 initial courses of chemotherapy receive 2 additional courses of chemotherapy as above. Patients with a CR to courses 3 and 4 receive 2 more courses of chemotherapy and then proceed to observational phase. Patients with a PR to courses 3 and 4 undergo a biopsy and/or resection of residual tumor.
- Patients with no evidence of malignant GCT on resection but with scar, fibrosis, or mature teratoma receive carboplatin IV over 4 hours and etoposide IV over 2 hours on days 1 and 2 and cyclophosphamide IV over 1 hour and etoposide IV over 2 hours on days 22 and 23 and proceed to observational phase. Patients with teratoma on resection receive additional treatment as in regimen A. Patients with evidence of pure germinoma on resection undergo radiotherapy.
- Patients with evidence of other malignant GCT on resection undergo high-dose chemotherapy (HDCx) with bone marrow or peripheral blood stem cell support (PBSCS) comprising thiotepa IV over 3 hours and etoposide IV over 1 hour on days -8 through -6; carboplatin IV over 4 hours on days -5 through -3; reinfusion of autologous bone marrow or peripheral blood stem cells on day 0; and G-CSF SC or IV every 12 hours beginning on day 1 and continuing until blood counts recover. Patients then undergo radiotherapy.
Quality of life is assessed before bone marrow or PBSCS and then every 2 years thereafter.
Patients are followed at day 42, at 3 months, then every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 80 patients (40 per stratum) will be accrued for this study within 4 years.
- Conditions
- Brain and Central Nervous System Tumors
- Being tested
- filgrastim, carboplatin, cyclophosphamide, etoposide, thiotepa
- Keywords
- childhood central nervous system germ cell tumor, adult central nervous system germ cell tumor
- Medical subject headings
- Central Nervous System Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
filgrastimBiological
carboplatinDrug
cyclophosphamideDrug
etoposideDrug
thiotepaDrug
autologous bone marrow transplantationProcedure or surgery
bone marrow ablation with stem cell supportProcedure or surgery
conventional surgeryProcedure or surgery
peripheral blood stem cell transplantationProcedure or surgery
radiation therapyRadiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startDec 2000
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Masking
- None (open label)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- Jonathan L. Finlay, MB, ChB, Study chair, Children's Hospital Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00025324
- Sponsor's protocol ID
- CDR0000068950
- Other IDs
- CHLA-NYU-0007H, NCI-G01-2019
- Status last verified
- Dec 2004
- First submitted
- 11 Oct 2001
- Last updated
- 18 Dec 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Correlative Studies In Primary Central Nervous System Germ Cell Tumors: The Third International CNS Germ Cell Tumor Study Group Protocol
- ClinicalTrials.gov ID
- NCT00025324
- Acronym / sponsor ID
- CDR0000068950
- Conditions
- Brain and Central Nervous System Tumors
- Keywords
- childhood central nervous system germ cell tumor, adult central nervous system germ cell tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Lead sponsor
- Children's Hospital Los AngelesUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Dec 2000
- First posted
- 27 Jan 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells.
PURPOSE: Phase II trial to study the effectiveness of chemotherapy, surgery, radiation therapy, and bone marrow or peripheral stem cell transplantation in treating patients who have primary CNS germ cell tumors.
Detailed description
OBJECTIVES:
- Determine the two-year event-free survival of patients with primary CNS germ cell tumors treated with carboplatin, etoposide, cyclophosphamide, and filgrastim (G-CSF) with or without radiotherapy and/or high-dose chemotherapy with autologous bone marrow or peripheral blood stem cell transplantation.
- Determine the prognostic significance of slow-responding tumor marker normalization in patients treated with this regimen.
- Determine the prognostic significance of syncytiotrophoblastic giant cell component and cerebrospinal fluid beta-human chorionic gonadotropin elevation in patients treated with this regimen.
- Assess the early and late endocrinologic, neuropsychometric, and quality of life sequelae in patients treated with this regimen.
OUTLINE: This is a multicenter study. Patients are stratified according to risk status (low vs intermediate or high).
Regimen A (Low-risk patients)
- Chemotherapy: Patients receive carboplatin IV over 4 hours and etoposide IV over 2 hours on days 1-2 and filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 3 and continuing until blood counts recover (course 1). Patients also receive cyclophosphamide IV over 1 hour and etoposide IV over 2 hours on days 22 and 23 and G-CSF SC once daily beginning on day 24 and continuing until blood counts recover (course 2).
- Patients with complete response (CR) to initial chemotherapy receive 2 additional courses of chemotherapy as above and then proceed to observational phase. Patients with partial response (PR) to initial chemotherapy receive 2 additional courses of chemotherapy as above.
- Patients with CR after additional chemotherapy receive another 2 additional courses of chemotherapy as above and then proceed to observational phase. Patients with PR after additional chemotherapy undergo biopsy and/or resection of residual tumor.
- Patients with evidence of malignant germ cell tumor (GCT) on resection undergo radiotherapy. Patients with no evidence of malignant GCT on resection but with scar, fibrosis, or mature teratoma receive 2 additional courses of chemotherapy as above and then proceed to observational phase. Patients with no evidence of malignant GCT on resection but with immature teratoma receive carboplatin IV over 4 hours, cyclophosphamide IV over 1 hour, and etoposide IV over 2 hours on days 1-2 and 22-23. Patients who underwent complete resection of residual tumor proceed to observational phase. Patients who underwent a biopsy only or an incomplete resection of residual tumor undergo radiotherapy.
Regimen B (Intermediate and high-risk patients)
- Patients receive carboplatin IV over 4 hours, cyclophosphamide IV over 1 hour, and etoposide IV over 2 hours on days 0-1. Patients also receive G-CSF SC once daily beginning on day 2 and continuing until blood counts recover. Treatment repeats every 21 days for a total of 2 courses. Patients undergo bone marrow or peripheral blood stem cell harvest prior to second course of chemotherapy.
- Patients with rapid CR to 2 initial courses of chemotherapy receive an additional 2 courses of chemotherapy as above and then proceed to observational phase. Patients with a PR or slow response to 2 initial courses of chemotherapy receive 2 additional courses of chemotherapy as above. Patients with a CR to courses 3 and 4 receive 2 more courses of chemotherapy and then proceed to observational phase. Patients with a PR to courses 3 and 4 undergo a biopsy and/or resection of residual tumor.
- Patients with no evidence of malignant GCT on resection but with scar, fibrosis, or mature teratoma receive carboplatin IV over 4 hours and etoposide IV over 2 hours on days 1 and 2 and cyclophosphamide IV over 1 hour and etoposide IV over 2 hours on days 22 and 23 and proceed to observational phase. Patients with teratoma on resection receive additional treatment as in regimen A. Patients with evidence of pure germinoma on resection undergo radiotherapy.
- Patients with evidence of other malignant GCT on resection undergo high-dose chemotherapy (HDCx) with bone marrow or peripheral blood stem cell support (PBSCS) comprising thiotepa IV over 3 hours and etoposide IV over 1 hour on days -8 through -6; carboplatin IV over 4 hours on days -5 through -3; reinfusion of autologous bone marrow or peripheral blood stem cells on day 0; and G-CSF SC or IV every 12 hours beginning on day 1 and continuing until blood counts recover. Patients then undergo radiotherapy.
Quality of life is assessed before bone marrow or PBSCS and then every 2 years thereafter.
Patients are followed at day 42, at 3 months, then every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 80 patients (40 per stratum) will be accrued for this study within 4 years.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| filgrastim | Biological | – |
| carboplatin | Drug | – |
| cyclophosphamide | Drug | – |
| etoposide | Drug | – |
| thiotepa | Drug | – |
| autologous bone marrow transplantation | Procedure or surgery | – |
| bone marrow ablation with stem cell support | Procedure or surgery | – |
| conventional surgery | Procedure or surgery | – |
| peripheral blood stem cell transplantation | Procedure or surgery | – |
| radiation therapy | Radiation | – |
Primary outcome
Not reported in the source record.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jonathan L. Finlay, MB, ChB study chair
Children's Hospital Los Angeles
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing filgrastim, carboplatin and cyclophosphamide in people with Brain and Central Nervous System Tumors, run by Children's Hospital Los Angeles at 4 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Australia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2013.