Anaplastic AstrocytomaPhase 2NCT00100802
Radiation Therapy, Temozolomide, and Lomustine in Treating Young Patients With Newly Diagnosed Gliomas
A Phase 2 study testing Laboratory Biomarker Analysis, Lomustine and Radiation Therapy in people with Anaplastic Astrocytoma and Central Nervous System Neoplasm, run by Children's Oncology Group at 1 site in United States.
Trial summary
This phase II trial is studying how well giving radiation therapy together with temozolomide and lomustine works in treating young patients with newly diagnosed gliomas. Radiation therapy uses high energy x-rays to kill tumor cells. Read more about this study
- Who is it for?
- Ages 3 to 21 years
- Conditions the study is for
- Anaplastic Astrocytoma, Central Nervous System Neoplasm, Glioblastoma
- What is being tested?
- Laboratory Biomarker Analysis, Lomustine and Radiation Therapy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 118 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Mar 2005to 30 Jun 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Histologically confirmed, newly diagnosed high-grade glioma of 1 of the following histologies:
- Anaplastic astrocytoma
- Glioblastoma multiforme
- Gliosarcoma
- Primary spinal cord malignant gliomas allowed
- No primary brainstem tumors
Show all 41Show fewer
- Has undergone surgical resection or biopsy of the tumor within the past 31 days
- Pre-operative and post-operative brain MRI with and without gadolinium-contrast OR pre-operative and post-operative spine MRI for spinal cord primaries
- Post-operative MRI not required for patients who undergo biopsy only
- No evidence of neuraxis dissemination
- Spine MRI and cerebrospinal fluid cytology required only if clinically indicated
- Performance status - Karnofsky 50-100% (for patients > 16 years of age)
- Performance status - Lansky 50-100% (for patients ≤ 16 years of age)
- At least 8 weeks
- Absolute neutrophil count ≥ 1,000/mm^3
- Platelet count ≥ 100,000/mm^3 (transfusion independent)
- Hemoglobin ≥ 8 g/dL (transfusions allowed)
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- ALT ≤ 2.5 times ULN
- Albumin ≥ 2 g/dL
- Creatinine ≤ 1.5 times ULN
- Creatinine clearance or radioisotope glomerular filtration rate ≥ lower limit of normal
- No evidence of dyspnea at rest
- No exercise intolerance
- Pulse oximetry ≥ 94% (if determination is clinically indicated)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 2 months after study participation
- Able to swallow oral medication
- Seizures allowed provided they are well controlled with anticonvulsants
- No hypersensitivity to temozolomide
- No prior biologic agents
- No prior chemotherapy
- Prior corticosteroids allowed
- No concurrent corticosteroids as an antiemetic
- Concurrent corticosteroids allowed only for treatment of increased intracranial pressure
- No concurrent radiotherapy using cobalt-60
- See Disease Characteristics
- No other prior treatment
- No concurrent phenobarbital or cimetidine
- No concurrent co-trimoxazole for Pneumocystis carinii pneumonia prophylaxis during study chemoradiotherapy
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Oncology Group
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Phase II Study of Concurrent Radiation and Temozolomide Followed By Temozolomide and CCNU in the Treatment of Children With High-Grade Glioma
This phase II trial is studying how well giving radiation therapy together with temozolomide and lomustine works in treating young patients with newly diagnosed gliomas. Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide and lomustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with temozolomide and lomustine after surgery may kill any remaining tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- Compare event-free survival of pediatric patients with newly diagnosed high-grade gliomas treated with adjuvant radiotherapy and temozolomide followed by temozolomide and lomustine with historical controls.
II. Determine the toxicity of this regimen in these patients. III. Correlate MGMT and p53 expression in tumor tissue with outcome in patients treated with this regimen.
IV. Correlate polymorphisms in GSTP1, GSTM1 and GSTT1 genes and GSTP1 protein expression in tumors with survival in patients treated with this regimen.
OUTLINE: This is a pilot, multicenter study.
CHEMORADIOTHERAPY: Patients receive oral temozolomide once daily on days 1-42. Patients also undergo concurrent radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33 and 36-40. Patients who did not undergo prior gross total resection also undergo boost radiotherapy once daily on days 43-47.
MAINTENANCE CHEMOTHERAPY: Four weeks after completion of chemoradiotherapy, patients receive oral temozolomide once daily on days 1-5 and oral lomustine on day 1. Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months for 1 year, every 6 months for 3 years and then annually thereafter.
- Conditions
- Anaplastic Astrocytoma, Central Nervous System Neoplasm, Glioblastoma, Gliosarcoma, Spinal Cord Neoplasm
- Being tested
- Laboratory Biomarker Analysis, Lomustine, Radiation Therapy, Temozolomide
- Medical subject headings
- Astrocytoma, Central Nervous System Neoplasms, Glioblastoma, Gliosarcoma, Spinal Cord Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
LomustineDrug
Also called 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea, 1-Nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-, Belustin, Belustine
Given PO
Radiation TherapyRadiation
Also called Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated
Undergo radiation therapy
TemozolomideDrug
Also called CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (lomustine, temozolomide, radiation therapy) | Experimental | Patients receive oral temozolomide once daily on days 1-42. Patients also undergo concurrent radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33 and 36-40. Patients who did not undergo prior gross total resection also undergo boost radiotherapy once daily on days 43-47. Four weeks after completion of chemoradiotherapy, patients receive oral temozolomide once daily on days 1-5 and oral lomustine on day 1. Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Receives: Other: Laboratory Biomarker Analysis; Drug: Lomustine; Radiation: Radiation Therapy; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
One Year Overall Survival
Estimated one year survival using the Kaplan-Meier methodology.
Measured: One year
Occurrence of Death Attributable to Complications of Protocol Therapy
Number of deaths due to complications of protocol therapy.
Measured: While receiving protocol therapy (up to 301 days excluding delays) or within 30 days of Termination of Protocol Therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2005 (estimated)
- Study start21 Mar 2005
- Primary completion1 Sep 2012
- Study completion30 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Anaplastic AstrocytomaStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- 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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 118 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Regina I Jakacki, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00100802
- Sponsor's protocol ID
- ACNS0423
- Other IDs
- NCI-2012-02645, ACNS0423, CDR0000407744, COG-ACNS0423, ACNS0423, ACNS0423, U10CA098543
- Status last verified
- Jan 2023
- First submitted
- 6 Jan 2005
- Last updated
- 15 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Pollack IF, Hamilton RL, Burger PC, Brat DJ, Rosenblum MK, Murdoch GH, Nikiforova MN, Holmes EJ, Zhou T, Cohen KJ, Jakacki RI; Children's Oncology Group. Akt activation is a common event in pediatric malignant gliomas and a potential adverse prognostic marker: a report from the Children's Oncology Group. J Neurooncol. 2010 Sep;99(2):155-63. doi: 10.1007/s11060-010-0297-3. Epub 2010 Jul 4.
PubMed 20607350Pollack IF, Hamilton RL, Sobol RW, Nikiforova MN, Nikiforov YE, Lyons-Weiler MA, LaFramboise WA, Burger PC, Brat DJ, Rosenblum MK, Gilles FH, Yates AJ, Zhou T, Cohen KJ, Finlay JL, Jakacki RI; Children's Oncology Group. Mismatch repair deficiency is an uncommon mechanism of alkylator resistance in pediatric malignant gliomas: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2010 Dec 1;55(6):1066-71. doi: 10.1002/pbc.22634.
PubMed 20589656Pollack IF, Hamilton RL, Sobol RW, Nikiforova MN, Lyons-Weiler MA, LaFramboise WA, Burger PC, Brat DJ, Rosenblum MK, Holmes EJ, Zhou T, Jakacki RI; Children's Oncology Group. IDH1 mutations are common in malignant gliomas arising in adolescents: a report from the Children's Oncology Group. Childs Nerv Syst. 2011 Jan;27(1):87-94. doi: 10.1007/s00381-010-1264-1. Epub 2010 Aug 20.
PubMed 20725730
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Concurrent Radiation and Temozolomide Followed By Temozolomide and CCNU in the Treatment of Children With High-Grade Glioma
- ClinicalTrials.gov ID
- NCT00100802
- Acronym / sponsor ID
- ACNS0423
- Conditions
- Anaplastic Astrocytoma, Central Nervous System Neoplasm, Glioblastoma, Gliosarcoma, Spinal Cord Neoplasm
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 118 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 21 Mar 2005 (actual)
- Primary completion
- 1 Sep 2012 (actual)
- Study completion
- 30 Jun 2017 (actual)
- First posted
- 7 Jan 2005 (estimated)
- Results
- Posted 13 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studying how well giving radiation therapy together with temozolomide and lomustine works in treating young patients with newly diagnosed gliomas. Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide and lomustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with temozolomide and lomustine after surgery may kill any remaining tumor cells.
Detailed description
PRIMARY OBJECTIVES:
- Compare event-free survival of pediatric patients with newly diagnosed high-grade gliomas treated with adjuvant radiotherapy and temozolomide followed by temozolomide and lomustine with historical controls.
II. Determine the toxicity of this regimen in these patients. III. Correlate MGMT and p53 expression in tumor tissue with outcome in patients treated with this regimen.
IV. Correlate polymorphisms in GSTP1, GSTM1 and GSTT1 genes and GSTP1 protein expression in tumors with survival in patients treated with this regimen.
OUTLINE: This is a pilot, multicenter study.
CHEMORADIOTHERAPY: Patients receive oral temozolomide once daily on days 1-42. Patients also undergo concurrent radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33 and 36-40. Patients who did not undergo prior gross total resection also undergo boost radiotherapy once daily on days 43-47.
MAINTENANCE CHEMOTHERAPY: Four weeks after completion of chemoradiotherapy, patients receive oral temozolomide once daily on days 1-5 and oral lomustine on day 1. Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months for 1 year, every 6 months for 3 years and then annually thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (lomustine, temozolomide, radiation therapy) | Experimental | Other: Laboratory Biomarker Analysis, Drug: Lomustine, Radiation: Radiation Therapy, Drug: TemozolomidePatients receive oral temozolomide once daily on days 1-42. Patients also undergo concurrent radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33 and 36-40. Patients who did not undergo prior gross total resection also undergo boost radiotherapy once daily on days 43-47. Four weeks after completion of chemoradiotherapy, patients receive oral temozolomide once daily on days 1-5 and oral lomustine on day 1. Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 3 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (41 listed)
- Histologically confirmed, newly diagnosed high-grade glioma of 1 of the following histologies:
- Primary spinal cord malignant gliomas allowed
- No primary brainstem tumors
- Has undergone surgical resection or biopsy of the tumor within the past 31 days
- No evidence of neuraxis dissemination
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (lomustine, temozolomide, radiation therapy) |
| LomustineAlso: 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea, 1-Nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-, Belustin, BelustineGiven PO | Drug | Treatment (lomustine, temozolomide, radiation therapy) |
| Radiation TherapyAlso: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, IrradiatedUndergo radiation therapy | Radiation | Treatment (lomustine, temozolomide, radiation therapy) |
| TemozolomideAlso: CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831Given PO | Drug | Treatment (lomustine, temozolomide, radiation therapy) |
Primary outcome
One Year Overall Survival
Time frame: One year
Estimated one year survival using the Kaplan-Meier methodology.
Occurrence of Death Attributable to Complications of Protocol Therapy
Time frame: While receiving protocol therapy (up to 301 days excluding delays) or within 30 days of Termination of Protocol Therapy
Number of deaths due to complications of protocol therapy.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20607350Pollack IF, Hamilton RL, Burger PC, Brat DJ, Rosenblum MK, Murdoch GH, Nikiforova MN, Holmes EJ, Zhou T, Cohen KJ, Jakacki RI; Children's Oncology Group. Akt activation is a common event in pediatric malignant gliomas and a potential adverse prognostic marker: a report from the Children's Oncology Group. J Neurooncol. 2010 Sep;99(2):155-63. doi: 10.1007/s11060-010-0297-3. Epub 2010 Jul 4.
- Background: PubMed 20589656Pollack IF, Hamilton RL, Sobol RW, Nikiforova MN, Nikiforov YE, Lyons-Weiler MA, LaFramboise WA, Burger PC, Brat DJ, Rosenblum MK, Gilles FH, Yates AJ, Zhou T, Cohen KJ, Finlay JL, Jakacki RI; Children's Oncology Group. Mismatch repair deficiency is an uncommon mechanism of alkylator resistance in pediatric malignant gliomas: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2010 Dec 1;55(6):1066-71. doi: 10.1002/pbc.22634.
- Results publication: PubMed 20725730Pollack IF, Hamilton RL, Sobol RW, Nikiforova MN, Lyons-Weiler MA, LaFramboise WA, Burger PC, Brat DJ, Rosenblum MK, Holmes EJ, Zhou T, Jakacki RI; Children's Oncology Group. IDH1 mutations are common in malignant gliomas arising in adolescents: a report from the Children's Oncology Group. Childs Nerv Syst. 2011 Jan;27(1):87-94. doi: 10.1007/s00381-010-1264-1. Epub 2010 Aug 20.
Related trials for Anaplastic Astrocytoma
Active, not recruitingPhase 2
Dabrafenib Combined With Trametinib After Radiation Therapy in Treating Patients With Newly-Diagnosed High-Grade Glioma
Anaplastic Astrocytoma, Anaplastic Astrocytoma, Not Otherwise Specified
RecruitingPhase 1/2
A Study of Zedoresertib (Debio 0123) in Combination With Temozolomide in Adult Participants With Recurrent or Progressive Glioblastoma and of Zedoresertib (Debio 0123) in Combination With Temozolomide and Radiotherapy in Adult Participants With Newly Diagnosed Glioblastoma
Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype, Astrocytoma, Grade III
RecruitingPhase 1
Phase I Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms
Central Nervous System Neoplasms, Glioblastoma
RecruitingEarly Phase 1
Implantable Microdevice In Primary Brain Tumors
Grade II Glioma, Grade III Glioma
Recruiting
Local, Targeted Therapy With Alpha Emitter [225Ac]Ac-DOTA-SP (TAT) in Glioma (WHO G3-G4) Progression
Glioblastoma, High-Grade Gliomas
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.
Regina I Jakacki principal investigator
Children's Oncology Group
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Laboratory Biomarker Analysis, Lomustine and Radiation Therapy in people with Anaplastic Astrocytoma and Central Nervous System Neoplasm, run by Children's Oncology Group 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?
The sponsor lists 41 inclusion and 0 exclusion criteria. 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: finished, as of the sponsor's last update on 15 Feb 2023. 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 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?
Yes. Results are posted in the registry (first posted 13 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
One Year Overall Survival (time frame: One year). The study lists 2 primary outcomes in all. 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 NCT00100802, which also lists 3 linked publications.
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 15 Feb 2023.