Brain and Central Nervous System TumorsPhase 3NCT00278278
Combination Chemotherapy and Radiation Therapy With or Without Methotrexate in Treating Young Patients With Newly Diagnosed Gliomas
A Phase 3 study testing cisplatin, etoposide and ifosfamide in people with Brain and Central Nervous System Tumors, run by German Society for Pediatric Oncology and Hematology GPOH gGmbH at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Read more about this study
- Who is it for?
- Ages 3 to 18 years
- Conditions the study is for
- Brain and Central Nervous System Tumors
- What is being tested?
- cisplatin, etoposide and ifosfamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2003to Mar 2010
- Phase
- Phase 3
- 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 3 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
DISEASE CHARACTERISTICS:
- Newly diagnosed tumors of the brain or spinal cord, meeting one of the following criteria:
- Histologically* confirmed diagnosis of 1 of the following high-grade gliomas:
- Glioblastoma (WHOº IV)
- Anaplastic astrocytoma (WHOº III)
- Gliosarcoma (WHOº III or IV)
- Anaplastic oligo-astrocytoma NOTE: *Histological requirement may be waived for other types of brainstem glioma
- Radiologically proven diffuse intrinsic pontine glioma
- Second malignancy or disseminate metastases or multifocal tumors are allowed if the field of irradiation is not too large
- No diffuse metastases making craniospinal irradiation necessary
PATIENT CHARACTERISTICS:
- No cardiorespiratory insufficiency requiring medical respiration
- No low blood pressure requiring systemic catecholamines
- No severe neurological damage (e.g., coma)
- No tetraplegia without possibility to communicate
- No other poor clinical condition
- Not pregnant
- Fertile patients must use effective contraception
- No hypersensitivity to methotrexate, cisplatin, vincristine, lomustine, or ifosfamide
- No other malignancy preceding radiotherapy that does not allow further radiation
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy for brain tumor
- The following prior therapies are allowed:
- Mistletoe
- H15 (extract of Boswellia serrata)
- Homeopathy therapy with dilution > 4D
- Alternative medicine without proven efficacy
- No prior radiotherapy for brain tumor
- No concurrent alcohol or tobacco consumption
- No concurrent participation in another study
Trial locations and contacts
1 site in 1 country.
United States1 site
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, 77030-4009
About this study
Official title: Treatment of Children and Adolescents With Diffuse Intrinsic Pontine Glioma and High Grade Glioma
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether giving methotrexate together with combination chemotherapy and radiation therapy is more effective than combination chemotherapy and radiation therapy alone in treating gliomas.
PURPOSE: This randomized phase III trial is studying giving methotrexate together with combination chemotherapy and radiation therapy to see how well it works compared to combination chemotherapy and radiation therapy alone in treating young patients with newly diagnosed gliomas.
Read the detailed description
OBJECTIVES:
Primary
- Determine if the addition of high-dose methotrexate prior to standard treatment improves survival of patients with malignant high-grade glioma or diffuse intrinsic pontine glioma as compared to standard treatment only.
Secondary
- Determine if the addition of high-dose methotrexate, as compared to standard treatment only, improves the tumor response of these patients.
- Determine if high-dose methotrexate, compared to standard treatment only, improves the progression-free or event-free survival of these patients.
- Determine if high-dose methotrexate, as compared to standard treatment only, improves the health status (quality of life) of these patients.
- Determine if consolidation therapy improves the overall, progression-free, or event-free survival rates as compared to the historical control group.
OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to tumor location includes pons (yes vs no) and complete or nearly complete resection (yes vs no).
- Surgery: All patients are encouraged to undergo radical resection of the tumor to reduce intracranial pressure, remove as much tumor tissue as possible, and obtain tumor tissue for histological diagnosis. Within 14 days after surgery, patients proceed to induction chemotherapy.
- Induction therapy: Patients are randomized to 1 of 2 treatment arms.
- Arm I:
- High-dose methotrexate with leucovorin calcium: Patients receive high-dose methotrexate IV over 24 hours on days 1 and 15 and leucovorin calcium IV every 6 hours on days 2-3 an 16-17. Patients proceed to chemoradiotherapy 4 weeks later.
- Chemoradiotherapy (course 1): Patients undergo external beam radiotherapy once daily, 5 days a week, for approximately 6 weeks. Beginning on the first day of radiotherapy, patients receive cisplatin IV over 1 hour on days 1-5, etoposide IV over 2 hours on days 1-3, and vincristine IV on days 5, 12, 19, 26, and 33. Patients proceed to course 2 of chemoradiotherapy 7 days prior to completion of radiotherapy.
- Chemoradiotherapy (course 2): Patients receive ifosfamide IV over 1 hour and cisplatin IV over 1 hour on days 1-5, etoposide IV over 2 hours on days 1-3, and vincristine IV on day 5. Patients proceed to consolidation chemotherapy 4 weeks later.
- Arm II: Patients receive chemoradiotherapy courses 1 and 2 as in arm I and proceed to consolidation chemotherapy 4 weeks later.
- Consolidation chemotherapy: Patients receive vincristine IV on days 1, 8, and 15, oral lomustine once on day 2, and oral prednisone once daily on days 1-17. Treatment repeats every 6 weeks for up to 8 courses.
Quality of life is assessed 1 week after surgery, after completion of chemoradiotherapy, at 1, 4, and 13 months after completion of consolidation chemotherapy, and then annually for 3 years.
After completion of study treatment, patients are followed periodically for 3 years.
PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study.
- Conditions
- Brain and Central Nervous System Tumors
- Being tested
- cisplatin, etoposide, ifosfamide, lomustine, methotrexate
- Keywords
- untreated childhood brain stem glioma, untreated childhood cerebellar astrocytoma, childhood high-grade cerebral astrocytoma, childhood spinal cord neoplasm
- Medical subject headings
- Central Nervous System Neoplasms, Astrocytoma, Spinal Cord Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cisplatinDrug
Given IV
etoposideDrug
Given IV
ifosfamideDrug
Given IV
lomustineDrug
Given IV
methotrexateDrug
Given IV
prednisoneDrug
Given IV
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients receive high-dose methotrexate IV over 24 hours on days 1 and 15 and leucovorin calcium IV every 6 hours on days 2-3 an 16-17. Four weeks later, patients undergo external beam radiotherapy once daily, 5 days a week, for approximately 6 weeks.
Beginning on the first day of radiotherapy, patients receive cisplatin IV over 1 hour on days 1-5, etoposide IV over 2 hours on days 1-3, and vincristine IV on days 5, 12, 19, 26, and 33. Beginning seven days prior to completion of radiotherapy, patients receive ifosfamide IV over 1 hour and cisplatin IV over 1 hour on days 1-5, etoposide IV over 2 hours on days 1-3, and vincristine IV on day 5. Receives: Drug: cisplatin; Drug: etoposide; Drug: ifosfamide; Drug: lomustine; Drug: methotrexate; Drug: prednisone; Drug: vincristine sulfate |
| Arm II | Active comparator | Patients undergo external beam radiotherapy once daily, 5 days a week, for approximately 6 weeks.
Beginning on the first day of radiotherapy, patients receive cisplatin IV over 1 hour on days 1-5, etoposide IV over 2 hours on days 1-3, and vincristine IV on days 5, 12, 19, 26, and 33. Beginning seven days prior to completion of radiotherapy, patients receive ifosfamide IV over 1 hour and cisplatin IV over 1 hour on days 1-5, etoposide IV over 2 hours on days 1-3, and vincristine IV on day 5. Receives: Drug: cisplatin; Drug: etoposide; Drug: ifosfamide; Drug: lomustine; Drug: prednisone; Drug: vincristine sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival (OS) rate at 5.5 years
Secondary outcomes (6)
Comparison of OS, progression-free survival, and event-free survival with historical control annually
Long-term sequelae annually
Tumor response
Progression-free survival
Event-free survival
Health status
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2006 (estimated)
- Study startSep 2003
- Primary completionMar 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- German Society for Pediatric Oncology and Hematology GPOH gGmbH
- Sponsor type
- University, hospital or other
- Investigators
- Christoph Kramm, MD, Study chair, University Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00278278
- Sponsor's protocol ID
- CDR0000454723
- Other IDs
- GPOH-HIT-GBM-D, EU-205100
- Status last verified
- Nov 2008
- First submitted
- 16 Jan 2006
- Last updated
- 19 Dec 2013
- Results posted
- No
Publications
Wolff JE, Kortmann RD, Wolff B, Pietsch T, Peters O, Schmid HJ, Rutkowski S, Warmuth-Metz M, Kramm C. High dose methotrexate for pediatric high grade glioma: results of the HIT-GBM-D pilot study. J Neurooncol. 2011 May;102(3):433-42. doi: 10.1007/s11060-010-0334-2. Epub 2010 Aug 8.
PubMed 20694800
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Children and Adolescents With Diffuse Intrinsic Pontine Glioma and High Grade Glioma
- ClinicalTrials.gov ID
- NCT00278278
- Acronym / sponsor ID
- CDR0000454723
- Conditions
- Brain and Central Nervous System Tumors
- Keywords
- untreated childhood brain stem glioma, untreated childhood cerebellar astrocytoma, childhood high-grade cerebral astrocytoma, childhood spinal cord neoplasm
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- German Society for Pediatric Oncology and Hematology GPOH gGmbHUniversity, hospital or other
- Study start
- Sep 2003
- Primary completion
- Mar 2010 (estimated)
- First posted
- 18 Jan 2006 (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 work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether giving methotrexate together with combination chemotherapy and radiation therapy is more effective than combination chemotherapy and radiation therapy alone in treating gliomas.
PURPOSE: This randomized phase III trial is studying giving methotrexate together with combination chemotherapy and radiation therapy to see how well it works compared to combination chemotherapy and radiation therapy alone in treating young patients with newly diagnosed gliomas.
Detailed description
OBJECTIVES:
Primary
- Determine if the addition of high-dose methotrexate prior to standard treatment improves survival of patients with malignant high-grade glioma or diffuse intrinsic pontine glioma as compared to standard treatment only.
Secondary
- Determine if the addition of high-dose methotrexate, as compared to standard treatment only, improves the tumor response of these patients.
- Determine if high-dose methotrexate, compared to standard treatment only, improves the progression-free or event-free survival of these patients.
- Determine if high-dose methotrexate, as compared to standard treatment only, improves the health status (quality of life) of these patients.
- Determine if consolidation therapy improves the overall, progression-free, or event-free survival rates as compared to the historical control group.
OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to tumor location includes pons (yes vs no) and complete or nearly complete resection (yes vs no).
- Surgery: All patients are encouraged to undergo radical resection of the tumor to reduce intracranial pressure, remove as much tumor tissue as possible, and obtain tumor tissue for histological diagnosis. Within 14 days after surgery, patients proceed to induction chemotherapy.
- Induction therapy: Patients are randomized to 1 of 2 treatment arms.
- Arm I:
- High-dose methotrexate with leucovorin calcium: Patients receive high-dose methotrexate IV over 24 hours on days 1 and 15 and leucovorin calcium IV every 6 hours on days 2-3 an 16-17. Patients proceed to chemoradiotherapy 4 weeks later.
- Chemoradiotherapy (course 1): Patients undergo external beam radiotherapy once daily, 5 days a week, for approximately 6 weeks. Beginning on the first day of radiotherapy, patients receive cisplatin IV over 1 hour on days 1-5, etoposide IV over 2 hours on days 1-3, and vincristine IV on days 5, 12, 19, 26, and 33. Patients proceed to course 2 of chemoradiotherapy 7 days prior to completion of radiotherapy.
- Chemoradiotherapy (course 2): Patients receive ifosfamide IV over 1 hour and cisplatin IV over 1 hour on days 1-5, etoposide IV over 2 hours on days 1-3, and vincristine IV on day 5. Patients proceed to consolidation chemotherapy 4 weeks later.
- Arm II: Patients receive chemoradiotherapy courses 1 and 2 as in arm I and proceed to consolidation chemotherapy 4 weeks later.
- Consolidation chemotherapy: Patients receive vincristine IV on days 1, 8, and 15, oral lomustine once on day 2, and oral prednisone once daily on days 1-17. Treatment repeats every 6 weeks for up to 8 courses.
Quality of life is assessed 1 week after surgery, after completion of chemoradiotherapy, at 1, 4, and 13 months after completion of consolidation chemotherapy, and then annually for 3 years.
After completion of study treatment, patients are followed periodically for 3 years.
PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: cisplatin, Drug: etoposide, Drug: ifosfamide, Drug: lomustine, Drug: methotrexate, Drug: prednisone, Drug: vincristine sulfatePatients receive high-dose methotrexate IV over 24 hours on days 1 and 15 and leucovorin calcium IV every 6 hours on days 2-3 an 16-17. Four weeks later, patients undergo external beam radiotherapy once daily, 5 days a week, for approximately 6 weeks. Beginning on the first day of radiotherapy, patients receive cisplatin IV over 1 hour on days 1-5, etoposide IV over 2 hours on days 1-3, and vincristine IV on days 5, 12, 19, 26, and 33. Beginning seven days prior to completion of radiotherapy, patients receive ifosfamide IV over 1 hour and cisplatin IV over 1 hour on days 1-5, etoposide IV over 2 hours on days 1-3, and vincristine IV on day 5. |
| Arm II | Active comparator | Drug: cisplatin, Drug: etoposide, Drug: ifosfamide, Drug: lomustine, Drug: prednisone, Drug: vincristine sulfatePatients undergo external beam radiotherapy once daily, 5 days a week, for approximately 6 weeks. Beginning on the first day of radiotherapy, patients receive cisplatin IV over 1 hour on days 1-5, etoposide IV over 2 hours on days 1-3, and vincristine IV on days 5, 12, 19, 26, and 33. Beginning seven days prior to completion of radiotherapy, patients receive ifosfamide IV over 1 hour and cisplatin IV over 1 hour on days 1-5, etoposide IV over 2 hours on days 1-3, and vincristine IV on day 5. |
Who may qualify
- Ages
- 3 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, 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 |
|---|---|---|
| cisplatinGiven IV | Drug | Arm I, Arm II |
| etoposideGiven IV | Drug | Arm I, Arm II |
| ifosfamideGiven IV | Drug | Arm I, Arm II |
| lomustineGiven IV | Drug | Arm I, Arm II |
| methotrexateGiven IV | Drug | Arm I |
| prednisoneGiven IV | Drug | Arm I, Arm II |
| vincristine sulfateGiven IV | Drug | Arm I, Arm II |
Primary outcome
Overall survival (OS) rate at 5.5 years
6 secondary outcomes
Comparison of OS, progression-free survival, and event-free survival with historical control annually
Long-term sequelae annually
Tumor response
Progression-free survival
Event-free survival
Health status
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2013.
- Results publication: PubMed 20694800Wolff JE, Kortmann RD, Wolff B, Pietsch T, Peters O, Schmid HJ, Rutkowski S, Warmuth-Metz M, Kramm C. High dose methotrexate for pediatric high grade glioma: results of the HIT-GBM-D pilot study. J Neurooncol. 2011 May;102(3):433-42. doi: 10.1007/s11060-010-0334-2. Epub 2010 Aug 8.
Related trials for Brain and Central Nervous System Tumors
RecruitingPhase 2
BrAin Metastasis in tripLe Negateive Breast Cancer: IvoneScimab and Trop2 ADC
Triple-Negative Breast Cancer (TNBC), Brain Metastases
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma
Recruiting
Virtual Home-based Exercise Intervention (RISE) to Improve Cancer-Related Cognitive Impairment and Gut Microbiome in Adolescent and Young Adult Brain Tumor Survivors
Cancer-related Cognitive Dysfunction, Primary Brain Neoplasm
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.
Christoph Kramm, MD study chair
University Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing cisplatin, etoposide and ifosfamide in people with Brain and Central Nervous System Tumors, run by German Society for Pediatric Oncology and Hematology GPOH gGmbH at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 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 1 site in United States. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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.
What does the primary outcome measure?
Overall survival (OS) rate at 5.5 years. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00278278, which also lists 1 linked publication.
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 19 Dec 2013.