Glioblastoma Multiforme/Anaplastic AstrocytomaPhase 1NCT00841555
Temozolomide and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Anaplastic Astrocytoma
A Phase 1 study testing temozolomide, Hypofractionated radiation therapy and Intensity-modulated radiation therapy in people with Glioblastoma Multiforme/Anaplastic Astrocytoma, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme/Anaplastic Astrocytoma
- What is being tested?
- temozolomide, Hypofractionated radiation therapy and Intensity-modulated radiation therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Feb 2009to 25 Nov 2014
- Phase
- Phase 1
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who have De novo glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendrogliomas, mixed anaplastic oligoastrocytomas, gliosarcoma of the Brain, not involving the brain stem or optics chiasm, diagnosed following biopsy or tumor removal.
- Age > 18 years
- Given written consent
- Adequate bone marrow reserve(hemoglobin > 10 grams, Absolute neutrophil count > 1500 / mm3, platelets > 100,000/ mm3)
- Normal renal function(BUN < 24 mg/dL, Creatinine < 1.3 mg/dL)
- Normal liver function(Total Bilirubin < 1.5 mg/dL, SGPT/ALT < 60 U/L)
Who cannot join
- Have a Karnofsky score of < 60 [Appendix B] or age < 18 years.
- Prior chemotherapy and/or radiotherapy of their glioblastomamultiforme, anaplastic astrocytoma, anaplastic oligodendrogliomas, mixed anaplastic oligoastrocytomas, gliosarcoma.
- Tumors located in the brainstem or optic chiasm.
- Prior radiation therapy to the brain
- Prior chemotherapy within the past 6 weeks.
Trial locations and contacts
1 site in 1 country.
United States1 site
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
About this study
Official title: A Phase I Trial of Hypofraction Radiotherapy + Temozolomide in the Treatment of Patients With Glioblastoma Multiforme and Anaplastic Astrocytoma of the Brain
RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving chemotherapy together with radiation therapy may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of temozolomide when given together with radiation therapy in treating patients with newly diagnosed glioblastoma multiforme or anaplastic astrocytoma.
Read the detailed description
OBJECTIVES:
Primary
- To determine the maximum tolerated dose of temozolomide when given in combination with hypofractionated intensity-modulated conformal stereotactic radiotherapy in patients with newly diagnosed de novo glioblastoma multiforme or anaplastic astrocytoma.
Secondary
- To determine the time to neuroradiological evidence of tumor recurrence or progression in patients treated with this regimen.
- To determine the survival time of patients treated with this regimen.
- To determine the time spent in a Karnofsky performance status of 60-100%.
OUTLINE: This is a dose-escalation study of temozolomide.
Beginning 1-3 weeks following surgery or biopsy, patients receive oral temozolomide once daily for 5 weeks. Beginning 1 week after starting temozolomide, patients also undergo hypofractionated intensity-modulated conformal stereotactic radiotherapy once daily 5 days a week for 3 weeks.
After completion of study treatment, patients are followed at 1 month, 2 months, and 3 months, and then every 3 months thereafter.
- Being tested
- temozolomide, Hypofractionated radiation therapy, Intensity-modulated radiation therapy
- Keywords
- adult giant cell glioblastoma, adult gliosarcoma, adult anaplastic astrocytoma, adult glioblastoma, GBM/AA
- Medical subject headings
- Glioblastoma, Astrocytoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
temozolomideDrug
Also called Temodar, Temodal
Chemotherapy will be given for 5 weeks; it will start 1 week before Radiotherapy, will continue for the 3 weeks of Radiotherapy, and will continue for 1 week post-Radiotherapy.
Dose Level 1: 50 mg/m2 x first 4 weeks/75 mg/m2 x last 1 weeks of treatment Dose Level 2: 65 mg/m2 x first 4 weeks/75 mg/m2 x last 1 weeks of treatment Dose Level 3: 75 mg/m2 over the entire 5 weeks of treatment
Hypofractionated radiation therapyRadiation
Patients will undergo HIMRT
Intensity-modulated radiation therapyRadiation
Also called IMRT
Patients undergo HIMRT
| Study group | Role | What they receive |
|---|---|---|
| Hypofractionation Radiotherapy+Temozolomide | Experimental | Patients will receive temozolomide PO daily for 5 weeks. Beginning week 1 after initiation of temozolomide therapy, patients undergo HIMRT times a week for a total of 15 fractions. Receives: Drug: temozolomide; Radiation: Hypofractionated radiation therapy; Radiation: Intensity-modulated radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose(MTD)of Temozolomide(TMZ)
This study is designed as a phase I dose escalation trial using the Standard Method of dose escalation of three patients per dose level to determine the MTD of TMZ (up to 75 mg/m 2 /day) when TMZ is used with HIMRT for patients with glioblastoma multiforme(GBM) or Anaplastic Astrocytoma(AA)of the brain. The 3 dose levels will be evaluated using the standard method to determine if either represents an MTD based on DLT. If DLT is not observed at all doses level, the greater of the three levels will be recommended for phase II evaluations of treatment effect.
Measured: up to 12-16 months
Secondary outcomes (3)
Time to Neuroradiological Evidence of Tumor Recurrence or Progression
As a small phase I study, no inferential statistical tests of hypotheses are planned. Data collected will be providing descriptive summary statistics. However, these estimates will allow statistically sound experimental designs and sample size calculations for subsequent studies of therapeutic effect.
Measured: up to 12-16 months
Survival Time
All patients will be followed to death. Active follow-up with disease evaluation with scans will be terminated if the patient's physician deems it in the patient's interest not to continue or upon patient request.
Measured: up to 2 years
Time Spent in a Karnofsky Performance Status of 60-100%
Time spent in a KPS ≥70 was calculated from the date of diagnosis of Karonofsky Performance Status decline (KPS<70) or censored at the last date the patient was known with KPS ≥70. The KPS higher scores indicates normal activity status.
Measured: up to 12-16 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2009 (estimated)
- Study start13 Feb 2009
- Primary completion13 Feb 2013
- Study completion25 Nov 2014
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 (1)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma Multiforme/Anaplastic AstrocytomaStudies of the same condition, open and under way.
- More trials run by Ohio State University Comprehensive Cancer CenterThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mario Ammirati, MD, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00841555
- Sponsor's protocol ID
- OSU-08119
- Other IDs
- NCI-2011-03149
- Status last verified
- Apr 2018
- First submitted
- 10 Feb 2009
- Last updated
- 18 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Ammirati M, Chotai S, Newton H, Lamki T, Wei L, Grecula J. Hypofractionated intensity modulated radiotherapy with temozolomide in newly diagnosed glioblastoma multiforme. J Clin Neurosci. 2014 Apr;21(4):633-7. doi: 10.1016/j.jocn.2013.09.005. Epub 2013 Oct 3.
PubMed 24380758
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Hypofraction Radiotherapy + Temozolomide in the Treatment of Patients With Glioblastoma Multiforme and Anaplastic Astrocytoma of the Brain
- ClinicalTrials.gov ID
- NCT00841555
- Acronym / sponsor ID
- OSU-08119
- Keywords
- adult giant cell glioblastoma, adult gliosarcoma, adult anaplastic astrocytoma, adult glioblastoma, GBM/AA
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Ohio State University Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 13 Feb 2009 (actual)
- Primary completion
- 13 Feb 2013 (actual)
- Study completion
- 25 Nov 2014 (actual)
- First posted
- 11 Feb 2009 (estimated)
- Results
- Posted 27 Apr 2016
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, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving chemotherapy together with radiation therapy may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of temozolomide when given together with radiation therapy in treating patients with newly diagnosed glioblastoma multiforme or anaplastic astrocytoma.
Detailed description
OBJECTIVES:
Primary
- To determine the maximum tolerated dose of temozolomide when given in combination with hypofractionated intensity-modulated conformal stereotactic radiotherapy in patients with newly diagnosed de novo glioblastoma multiforme or anaplastic astrocytoma.
Secondary
- To determine the time to neuroradiological evidence of tumor recurrence or progression in patients treated with this regimen.
- To determine the survival time of patients treated with this regimen.
- To determine the time spent in a Karnofsky performance status of 60-100%.
OUTLINE: This is a dose-escalation study of temozolomide.
Beginning 1-3 weeks following surgery or biopsy, patients receive oral temozolomide once daily for 5 weeks. Beginning 1 week after starting temozolomide, patients also undergo hypofractionated intensity-modulated conformal stereotactic radiotherapy once daily 5 days a week for 3 weeks.
After completion of study treatment, patients are followed at 1 month, 2 months, and 3 months, and then every 3 months thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hypofractionation Radiotherapy+Temozolomide | Experimental | Drug: temozolomide, Radiation: Hypofractionated radiation therapy, Radiation: Intensity-modulated radiation therapyPatients will receive temozolomide PO daily for 5 weeks. Beginning week 1 after initiation of temozolomide therapy, patients undergo HIMRT times a week for a total of 15 fractions. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients who have De novo glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendrogliomas, mixed anaplastic oligoastrocytomas, gliosarcoma of the Brain, not involving the brain stem or optics chiasm, diagnosed following biopsy or tumor removal.
- Age > 18 years
- Given written consent
- Adequate bone marrow reserve(hemoglobin > 10 grams, Absolute neutrophil count > 1500 / mm3, platelets > 100,000/ mm3)
- Normal renal function(BUN < 24 mg/dL, Creatinine < 1.3 mg/dL)
Key exclusion criteria (5 listed)
- Have a Karnofsky score of < 60 [Appendix B] or age < 18 years.
- Prior chemotherapy and/or radiotherapy of their glioblastomamultiforme, anaplastic astrocytoma, anaplastic oligodendrogliomas, mixed anaplastic oligoastrocytomas, gliosarcoma.
- Tumors located in the brainstem or optic chiasm.
- Prior radiation therapy to the brain
- Prior chemotherapy within the past 6 weeks.
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 |
|---|---|---|
| temozolomideAlso: Temodar, TemodalChemotherapy will be given for 5 weeks; it will start 1 week before Radiotherapy, will continue for the 3 weeks of Radiotherapy, and will continue for 1 week post-Radiotherapy. Dose Level 1: 50 mg/m2 x first 4 weeks/75 mg/m2 x last 1 weeks of treatment Dose Level 2: 65 mg/m2 x first 4 weeks/75 mg/m2 x last 1 weeks of treatment Dose Level 3: 75 mg/m2 over the entire 5 weeks of treatment | Drug | Hypofractionation Radiotherapy+Temozolomide |
| Hypofractionated radiation therapyPatients will undergo HIMRT | Radiation | Hypofractionation Radiotherapy+Temozolomide |
| Intensity-modulated radiation therapyAlso: IMRTPatients undergo HIMRT | Radiation | Hypofractionation Radiotherapy+Temozolomide |
Primary outcome
Maximum Tolerated Dose(MTD)of Temozolomide(TMZ)
Time frame: up to 12-16 months
This study is designed as a phase I dose escalation trial using the Standard Method of dose escalation of three patients per dose level to determine the MTD of TMZ (up to 75 mg/m 2 /day) when TMZ is used with HIMRT for patients with glioblastoma multiforme(GBM) or Anaplastic Astrocytoma(AA)of the brain. The 3 dose levels will be evaluated using the standard method to determine if either represents an MTD based on DLT. If DLT is not observed at all doses level, the greater of the three levels will be recommended for phase II evaluations of treatment effect.
3 secondary outcomes
Time to Neuroradiological Evidence of Tumor Recurrence or Progression
Time frame: up to 12-16 months
Survival Time
Time frame: up to 2 years
Time Spent in a Karnofsky Performance Status of 60-100%
Time frame: up to 12-16 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24380758Ammirati M, Chotai S, Newton H, Lamki T, Wei L, Grecula J. Hypofractionated intensity modulated radiotherapy with temozolomide in newly diagnosed glioblastoma multiforme. J Clin Neurosci. 2014 Apr;21(4):633-7. doi: 10.1016/j.jocn.2013.09.005. Epub 2013 Oct 3.
- JameslineLink provided by the sponsor.
Related trials for Glioblastoma Multiforme/Anaplastic Astrocytoma
RecruitingObservational study
Targeted Pediatric High-Grade Glioma Therapy
High Grade Glioma, Diffuse Intrinsic Pontine Glioma
Active, not recruitingPhase 1/2
A Phase I Study of Mebendazole for the Treatment of Pediatric Gliomas
Pilomyxoid Astrocytoma, Pilocytic Astrocytoma
RecruitingEarly Phase 1
Lorlatinib for Newly-Diagnosed High-Grade Glioma With ROS or ALK Fusion
High Grade Glioma, Diffuse Intrinsic Pontine Glioma
RecruitingObservational study
Loupe-Based Intraoperative Fluorescence Imaging
Glioblastoma Multiforme, Anaplastic Astrocytoma
Active, not recruitingPhase 1
A Pilot Study of SurVaxM in Children Progressive or Relapsed Medulloblastoma, High Grade Glioma, Ependymoma and Newly Diagnosed Diffuse Intrinsic Pontine Glioma
Medulloblastoma, Glioblastoma Multiforme
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.
Mario Ammirati, MD principal investigator
Ohio State University Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing temozolomide, Hypofractionated radiation therapy and Intensity-modulated radiation therapy in people with Glioblastoma Multiforme/Anaplastic Astrocytoma, run by Ohio State University Comprehensive Cancer Center 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 6 inclusion and 5 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 18 Apr 2018. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 27 Apr 2016). 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?
Maximum Tolerated Dose(MTD)of Temozolomide(TMZ) (time frame: up to 12-16 months). 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 NCT00841555, 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 18 Apr 2018; AzTrials last refreshed its copy on 7 Nov 2026.