High Grade GliomaPhase 2NCT01466686
Low Dose Radiation Therapy for Glioblastoma Multiforme
A Phase 2 study testing Low Dose Fractionated Radiation Therapy (LDFRT) and Temozolomide in people with High Grade Glioma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 3 sites in United States.
Trial summary
To evaluate the safety and effectiveness of low dose rate radiation therapy plus temozolomide. This will be in patients with High Grade Glioma (to only include Anaplastic Astrocytoma or Glioblastoma Multiforme) who have previously been treated with surgery followed by radiation surgical resection followed by adjuvant… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- High Grade Glioma
- What is being tested?
- Low Dose Fractionated Radiation Therapy (LDFRT) and Temozolomide
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 3 sitesUnited States
- Study dates
- Sep 2012to Dec 2022
- 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 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have recurrent GBM (Glioblastoma Multiforme)or Anaplastic Astrocytoma.
- The diagnosis of GBM or Anaplastic Astrocytoma.
- Patients must have been previously treated with surgical resection (any extent okay) and adjuvant radiation therapy plus temozolomide.
- Patients must be at least 12 months from completion of radiation therapy
- At least 2 months from completion of temozolomide (to be consistent with the the "rechallenge" group from Perry et al. JCO 2010).
- Age >18 years
Show all 13Show fewer
- ECOG performance status <2 (Karnofsky >60%, see appendix A).
- There must be measurable disease on MRI.
- Patients must have normal organ and marrow function as defined below:
- Women must not be pregnant
- Ability to understand and the willingness to sign a written informed consent document
- Temozolomide re-treatment is planned by the treating neuro-oncologist.
- The most recent brain tumor pathology obtained for the patient must be glioblastoma.
Who cannot join
- Must be able to receive an MRI
- Patients may not be receiving any other investigational cancer treatment agents at the time of enrollment.
- Patients may not have previously failed treatment with salvage temozolomide.
- Patients may not have previously failed treatment with a VEGF inhibitor.
- Patients may not have previously been treated with >1 course of radiotherapy.
- Patients may not have previously been treated with radiosurgery to the brain.
- Uncontrolled intercurrent illness
- Pregnant and breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use and acceptable method of birth control to avoid pregnancy for the entire study period and up to 12 weeks after the study are excluded. Male subjects must also agree to use effective contraception for the same period as above.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231
Suburban Hospital
Bethesda, Maryland, 20814
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016
About this study
Official title: A Phase II Trial of Low Dose Fractionated Radiation Therapy as a Chemo-Potentiator of Salvage Temozolomide for Recurrent Anaplastic Astrocytoma and Glioblastoma Multiforme
To evaluate the safety and effectiveness of low dose rate radiation therapy plus temozolomide. This will be in patients with High Grade Glioma (to only include Anaplastic Astrocytoma or Glioblastoma Multiforme) who have previously been treated with surgery followed by radiation surgical resection followed by adjuvant radiation therapy plus temozolomide.
Read the detailed description
In vitro and in vivo studies have suggested that low dose fractionated radiation therapy (LDFRT) may be used to potentiate full dose chemotherapy, decreasing the development of resistance found with standard doses of radiation and chemotherapy. This is a nonrandomized, open label, single institution phase II trial with a safety run-in to evaluate the safety and efficacy of LDFRT plus temozolomide in patients with High Grade Glioma (to only include Anaplastic Astrocytoma or Glioblastoma Multiforme) previously treated with surgical resection followed by adjuvant radiation therapy plus temozolomide. The primary objective of the phase II study is to estimate response rate in patients treated with twice daily fractions of low dose radiation plus temozolomide chemotherapy.
- Conditions
- High Grade Glioma
- Being tested
- Low Dose Fractionated Radiation Therapy (LDFRT), Temozolomide
- Keywords
- Recurrent Glioblastoma Multiforme, Recurrent Anaplastic Astrocytoma, Surgery, Adjuvant Radiation, Adjuvant Temozolomide
- Medical subject headings
- Glioma, Glioblastoma, Astrocytoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low Dose Fractionated Radiation Therapy (LDFRT)Radiation
All patients will receive 0.5 Gy of radiation therapy twice daily. This study will include a safety run-in component. If > 33% of patients in the initial cohort of 6 experience grade 3 or greater hematologic toxicity according to the NCI Common Toxicity Criteria version 4, then a dose reduction will occur following the schedule listed below.
TemozolomideDrug
All patients will receive temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle) for a total of 1 year or until the time of disease progression.
| Study group | Role | What they receive |
|---|---|---|
| Temozolomide with Low Dose Fractionated Radiation Therapy | Experimental | All patients will receive temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle) for a total of 1 year or until the time of disease progression.
All patients will receive 0.5 Gy of radiation therapy twice daily. This study will include a safety run-in component. If > 33% of patients in the initial cohort of 6 experience grade 3 or greater hematologic toxicity according to the NCI Common Toxicity Criteria version 4, then a dose reduction will occur following the schedule listed below. Otherwise, following a 1 month waiting period after the first cycle of adjuvant LDFRT plus temozolomide for the first cohort of patients, the phase 2 study will open for full accrual. Patients will receive radiation with the first six 28-day cycles of temozolomide. Receives: Radiation: Low Dose Fractionated Radiation Therapy (LDFRT); Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate
To estimate the response rate to salvage temozolomide plus LDFRT.
Measured: 3, 6 and 12 month follow-up after therapy has been completed
Overall Survival Rate
Overall survival rate is calculated as the median number of months that patients were alive for the cohort
Measured: up to 12 months after completion of temozolomide (48 weeks of treatment)
Secondary outcomes (3)
Progression Free Survival Rate
Progression free survival rate is calculated as the median number of months for the cohort until patient's disease worsened/progressed
Measured: up to 12 months after completion of temozolomide (48 weeks of treatment)
Number of Patients With Hematologic Toxicities
The number of patients with grade 3+ hematologic toxicities.
Measured: Approximately every month from study start until 48 weeks, and then up to 12 months after completion of temozolomide at 3, 6, and 12 months follow up
Number of Patients With Neurologic Toxicity
The number of patients with reported grade 3+ neurologic toxicities
Measured: Approximately every month from study start until 48 weeks, and then up to 12 months after completion of temozolomide at 3, 6, and 12 months follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2011 (estimated)
- Study startSep 2012
- Primary completionDec 2021
- Study completionDec 2022
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.
- Other trials for High Grade GliomaStudies 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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kristin Redmond, M.D., Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01466686
- Sponsor's protocol ID
- J11120
- Other IDs
- NA_00065863
- Status last verified
- Jun 2023
- First submitted
- 3 Nov 2011
- Last updated
- 3 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Low Dose Fractionated Radiation Therapy as a Chemo-Potentiator of Salvage Temozolomide for Recurrent Anaplastic Astrocytoma and Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT01466686
- Acronym / sponsor ID
- J11120
- Conditions
- High Grade Glioma
- Keywords
- Recurrent Glioblastoma Multiforme, Recurrent Anaplastic Astrocytoma, Surgery, Adjuvant Radiation, Adjuvant Temozolomide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Study start
- Sep 2012 (actual)
- Primary completion
- Dec 2021 (actual)
- Study completion
- Dec 2022 (actual)
- First posted
- 8 Nov 2011 (estimated)
- Results
- Posted 3 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the safety and effectiveness of low dose rate radiation therapy plus temozolomide. This will be in patients with High Grade Glioma (to only include Anaplastic Astrocytoma or Glioblastoma Multiforme) who have previously been treated with surgery followed by radiation surgical resection followed by adjuvant radiation therapy plus temozolomide.
Detailed description
In vitro and in vivo studies have suggested that low dose fractionated radiation therapy (LDFRT) may be used to potentiate full dose chemotherapy, decreasing the development of resistance found with standard doses of radiation and chemotherapy. This is a nonrandomized, open label, single institution phase II trial with a safety run-in to evaluate the safety and efficacy of LDFRT plus temozolomide in patients with High Grade Glioma (to only include Anaplastic Astrocytoma or Glioblastoma Multiforme) previously treated with surgical resection followed by adjuvant radiation therapy plus temozolomide. The primary objective of the phase II study is to estimate response rate in patients treated with twice daily fractions of low dose radiation plus temozolomide chemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Temozolomide with Low Dose Fractionated Radiation Therapy | Experimental | Radiation: Low Dose Fractionated Radiation Therapy (LDFRT), Drug: TemozolomideAll patients will receive temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle) for a total of 1 year or until the time of disease progression. All patients will receive 0.5 Gy of radiation therapy twice daily. This study will include a safety run-in component. If > 33% of patients in the initial cohort of 6 experience grade 3 or greater hematologic toxicity according to the NCI Common Toxicity Criteria version 4, then a dose reduction will occur following the schedule listed below. Otherwise, following a 1 month waiting period after the first cycle of adjuvant LDFRT plus temozolomide for the first cohort of patients, the phase 2 study will open for full accrual. Patients will receive radiation with the first six 28-day cycles of temozolomide. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients must have recurrent GBM (Glioblastoma Multiforme)or Anaplastic Astrocytoma.
- The diagnosis of GBM or Anaplastic Astrocytoma.
- Patients must have been previously treated with surgical resection (any extent okay) and adjuvant radiation therapy plus temozolomide.
- Patients must be at least 12 months from completion of radiation therapy
- At least 2 months from completion of temozolomide (to be consistent with the the "rechallenge" group from Perry et al. JCO 2010).
Key exclusion criteria (8 listed)
- Must be able to receive an MRI
- Patients may not be receiving any other investigational cancer treatment agents at the time of enrollment.
- Patients may not have previously failed treatment with salvage temozolomide.
- Patients may not have previously failed treatment with a VEGF inhibitor.
- Patients may not have previously been treated with >1 course of radiotherapy.
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 |
|---|---|---|
| Low Dose Fractionated Radiation Therapy (LDFRT)All patients will receive 0.5 Gy of radiation therapy twice daily. This study will include a safety run-in component. If > 33% of patients in the initial cohort of 6 experience grade 3 or greater hematologic toxicity according to the NCI Common Toxicity Criteria version 4, then a dose reduction will occur following the schedule listed below. | Radiation | Temozolomide with Low Dose Fractionated Radiation Therapy |
| TemozolomideAll patients will receive temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle) for a total of 1 year or until the time of disease progression. | Drug | Temozolomide with Low Dose Fractionated Radiation Therapy |
Primary outcome
Response Rate
Time frame: 3, 6 and 12 month follow-up after therapy has been completed
To estimate the response rate to salvage temozolomide plus LDFRT.
Overall Survival Rate
Time frame: up to 12 months after completion of temozolomide (48 weeks of treatment)
Overall survival rate is calculated as the median number of months that patients were alive for the cohort
3 secondary outcomes
Progression Free Survival Rate
Time frame: up to 12 months after completion of temozolomide (48 weeks of treatment)
Number of Patients With Hematologic Toxicities
Time frame: Approximately every month from study start until 48 weeks, and then up to 12 months after completion of temozolomide at 3, 6, and 12 months follow up
Number of Patients With Neurologic Toxicity
Time frame: Approximately every month from study start until 48 weeks, and then up to 12 months after completion of temozolomide at 3, 6, and 12 months follow up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Kristin Redmond, M.D. principal investigator
Johns Hopkins University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Low Dose Fractionated Radiation Therapy (LDFRT) and Temozolomide in people with High Grade Glioma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 3 sites 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 13 inclusion and 8 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 3 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 3 Jul 2023). 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?
Response Rate (time frame: 3, 6 and 12 month follow-up after therapy has been completed). 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?
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 3 Jul 2023.