AstrocytomaPhase 1NCT06344130
Hypofractionation Trial of Re-irradiation in Good Prognosis Recurrent Glioblastoma
A Phase 1 study testing Radiation Therapy in people with Astrocytoma and Glioma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: Glioblastoma (GBM) is a cancer of the brain. Current survival rates for people with GBM are poor; survival ranges from 5.2 months to 39 months. Most tumors come back within months or years after treatment, and when they do, they are worse: Overall survival drops to less than 10 months. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Astrocytoma, Glioma, Recurrent Glioblastoma
- What is being tested?
- Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2024to 31 Dec 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologic diagnosis of primary glioblastoma or gliosarcoma of the brain, or secondary glioblastoma of the brain due to transformation from a lower grade to a grade 4 tumor.
- Age >= 18.
- KPS >= 70%.
- Previous tumor irradiation to curative-intent doses.
- Radiation dose constraints must be achievable based on assessment with MRI and treatment planning CT.
- Participants must have adequate organ and marrow function as defined below:
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- Absolute neutrophil count (ANC) >= 1,000/microL
- Platelets >= 100,000/microL
- Individuals of child-bearing potential (IOCBP) and individuals who can father children must agree to use effective contraception (barrier, hormonal, intrauterine device, surgical sterilization, abstinence) from study entry and through 6 months after the last study treatment (restricted period). Individuals who can father children must not freeze or donate sperm within the same period.
- Nursing participants must be willing to discontinue nursing from study treatment initiation through 6 months after the last study treatment.
- The ability of a participant to understand and the willingness to sign a written informed consent document.
Who cannot join
- Recent systemic therapy prior to the initiation of the study therapy as follows:
- Bevacizumab used for reasons other than tumor progression or symptomatic management within 2 weeks.
- Temozolomide within 2 weeks.
- Cytotoxic chemotherapy within 3 weeks.
- Any investigational agents within 2 weeks.
- Participants who are unable to undergo MRI evaluation or receive gadolinium contrast for any reason.
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- Any prior therapy after surgical re-resection or biopsy within 2 weeks prior to the initiation of the study therapy.
- Requiring radiation therapy within 12 months prior to the initiation of study therapy.
- History of prior therapy with Novacure TTF, Gliadel wafers, or GammaTile therapy.
- Positive beta-human chorionic gonadotropin (HCG) pregnancy test performed in individuals of childbearing potential at screening.
- Participants with known or suspected radiation sensitivity syndromes.
- Uncontrolled intercurrent illness evaluated by medical history and physical exam that are not stable and would potentially increase the risk to the participant.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
National Cancer Institute Referral Office, 888-624-1937
About this study
Official title: A Phase I Hypofractionation Trial of Re-irradiation in Good Prognosis Recurrent Glioblastoma
Background:
Glioblastoma (GBM) is a cancer of the brain. Current survival rates for people with GBM are poor; survival ranges from 5.2 months to 39 months. Most tumors come back within months or years after treatment, and when they do, they are worse: Overall survival drops to less than 10 months. No standard treatment exists for people whose GBM has returned after radiation therapy.
Read more
Objective:
To find a safe schedule for using radiation to treat GBM tumors that returned after initial radiation treatment.
Eligibility:
People aged 18 years and older with grade 4 GBM that returned after initial radiation treatment.
Design:
Participants will be screened. They will have a physical exam with blood tests. A sample of tumor tissue may be collected.
Participants will undergo re-irradiation planning: They will wear a plastic mask over their head during imaging scans. These scans will pinpoint the exact location of the tumor. This spot will be the target of the radiation treatments.
Participants will undergo radiation treatment 4 times per week. Some people will have this treatment for 3 weeks, some for 2 weeks, and some for 1 week. Blood tests and other exams will be repeated at each visit.
Participants will complete questionnaires about their physical and mental health. They will answer these questions before starting radiation treatment; once a week during treatment; and at intervals for up to 3 years after treatment ends.
Participants will have follow-up visits 1 month after treatment and then every 2 months for 6 months. Follow-up clinic visits will continue up to 3 years. Follow-ups by phone or email will continue an additional 2 years.
Read the detailed description
Background:
- Although survival of glioblastoma (GBM) has improved using standard of care chemoradiation, outcomes are still poor. Most patients will recur within months to years, in or adjacent to their previous treatment field.
- There is no consensus standard of care for patients with recurrent GBM. Re-resection is recommended, if possible, to improve symptoms and decrease tumor volume. However, this treatment option is possible only in a minority of patients, and for these patients re-irradiation has emerged as a possible treatment.
- Modern radiation therapy (RT) techniques allow delivery of re-irradiation while minimizing the dose to previously treated organs at risk (OAR) within the radiation field.
- Data from a recently completed clinical trial at our center (16-C-0081, NCT02709226) suggests that the Maximum Tolerated Dose (MTD) of re-irradiation in 350 cGy fractions is 4200 cGy.
Objective:
-To determine the maximum tolerated dosage of daily re-irradiation in participants with recurrent Grade 4 gliomas
Eligibility:
- A histologic diagnosis of GBM, gliosarcoma, or transformation, from a lower grade to a grade 4 brain tumor.
- Previous glioma irradiation to curative-intent doses.
- Age >= 18.
- Karnofsky performance scale (KPS) >= 70.
Design:
- This is a single center phase I trial using a '3 + 3' design and a three (3) dose level hypofractionation schema to enroll a maximum of 21 evaluable participants.
- Prior to radiation therapy, participants will undergo laboratory evaluations, magnetic resonance imaging (MRI), and a treatment planning computed tomography (CT).
- RT will be administered daily 4 days a week for 1, 2, or 3 weeks in the Radiation Oncology Branch, NCI, at NIH. Radiation will be delivered on consecutive days, 4 fractions per week via a linear accelerator using 6 megavoltage (MV) photons or greater.
- Follow-up visits following RT are planned at 1 month, every 2 months for years 1-2, and every 3 months for year 3. These visits will be stopped earlier in case of progression. After progression or 3 years of follow-up, participants will be followed remotely for survival until 5 years after treatment completion.
- Conditions
- Astrocytoma, Glioma, Recurrent Glioblastoma
- Being tested
- Radiation Therapy
- Keywords
- Radiotherapy, Hypofractionation, Re-irradiation
- Medical subject headings
- Astrocytoma, Glioma, Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radiation TherapyRadiation
Radiation therapy will be administered via a linear accelerator using 6 megavoltage (MV) photons or greater.
| Study group | Role | What they receive |
|---|---|---|
| 1/Arm 1 | Experimental | Fraction size escalation of 3 planned re-irradiation dose levels. Receives: Radiation: Radiation Therapy |
| 2/Arm 2 | Experimental | MTD of re-irradiation dose. Receives: Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD of daily re-irradiation in participants with recurrent grade 4 gliomas
The number of participants experiencing DLTs within the DLT period will be reported for each hypofractionation schema. The MTD will be identified, and the proportion of participants treated with the MTD experiencing DLT will be reported.
Measured: DLT period (28 days)
Secondary outcomes (6)
Progression free survival
Time to progression is defined as the interval from the initiation of treatment on protocol to progression or death. Estimates of the median time to progression and of the proportion of participants experiencing progression by 3 years or dying by 5 years will be obtained.
Measured: Baseline, 30 day safety follow up visit, every 2 months for 2 years, every 3 months for 3rd year, or until progression
Overall survival
Overall survival is defined as the interval from initiation of treatment on protocol to the death. Estimates of the median time to overall survival will be obtained.
Measured: Treatment and follow up
Compliance and feasibility of administering PRO in this participant population
Patient reported outcome forms will be checked versus the timing schedule and considered valid if they fall within the scheduled assessment window. Compliance rates, namely the number of received valid forms over the number of expected forms will be reported.
Measured: Baseline through 3 years post radiation therapy.
Tolerability of treatment by assessing adverse events, cognitive function, physical function, and side effect bother
Tolerability of treatment will be assessed by determining the frequency of adverse events among treated participants and reporting the results by maximum grade of event and type of toxicity noted.
Measured: First radiation treatment administration through 6 months after the last day of radiation. Beyond 6 months after radiation, only adverse events which are serious and related to radiation need to be recorded.
Longitudinally describe and evaluate disease and treatment-related symptom severity and interference with daily activities
Longitudinal changes in perceived cognition, disease and treatment-related symptom severity, and interference with daily activities will be evaluated and described. The proportion of participants rating their symptoms as mild , moderate, or severe for individual symptoms will be reported.
Measured: Baseline through 3 years post radiation therapy.
Meaningful change in disease and treatment-related symptoms by using anchors
Meaningful change will be determined through both clinician-rated (Karnofsky) and participant-rated (PGI-Severity, PGI-Change) anchors from the MD Anderson Symptom Inventory for Brain Tumors and Montreal Cognitive Assessment.
Measured: Baseline through 3 years post radiation therapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2024
- Study start1 Oct 2024
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AstrocytomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 28 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Peter GK Mathen, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06344130
- Sponsor's protocol ID
- 10001859
- Other IDs
- 001859-C
- Status last verified
- 13 Oct 2026
- First submitted
- 2 Apr 2024
- Last updated
- 16 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD recorded in the medical record will be shared with intramural investigators upon request. This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review.
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Hypofractionation Trial of Re-irradiation in Good Prognosis Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT06344130
- Acronym / sponsor ID
- 10001859
- Conditions
- Astrocytoma, Glioma, Recurrent Glioblastoma
- Keywords
- Radiotherapy, Hypofractionation, Re-irradiation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 28 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 1 Oct 2024 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 3 Apr 2024 (actual)
- 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.
Background:
Glioblastoma (GBM) is a cancer of the brain. Current survival rates for people with GBM are poor; survival ranges from 5.2 months to 39 months. Most tumors come back within months or years after treatment, and when they do, they are worse: Overall survival drops to less than 10 months. No standard treatment exists for people whose GBM has returned after radiation therapy.
Objective:
To find a safe schedule for using radiation to treat GBM tumors that returned after initial radiation treatment.
Eligibility:
People aged 18 years and older with grade 4 GBM that returned after initial radiation treatment.
Design:
Participants will be screened. They will have a physical exam with blood tests. A sample of tumor tissue may be collected.
Participants will undergo re-irradiation planning: They will wear a plastic mask over their head during imaging scans. These scans will pinpoint the exact location of the tumor. This spot will be the target of the radiation treatments.
Participants will undergo radiation treatment 4 times per week. Some people will have this treatment for 3 weeks, some for 2 weeks, and some for 1 week. Blood tests and other exams will be repeated at each visit.
Participants will complete questionnaires about their physical and mental health. They will answer these questions before starting radiation treatment; once a week during treatment; and at intervals for up to 3 years after treatment ends.
Participants will have follow-up visits 1 month after treatment and then every 2 months for 6 months. Follow-up clinic visits will continue up to 3 years. Follow-ups by phone or email will continue an additional 2 years.
Detailed description
Background:
- Although survival of glioblastoma (GBM) has improved using standard of care chemoradiation, outcomes are still poor. Most patients will recur within months to years, in or adjacent to their previous treatment field.
- There is no consensus standard of care for patients with recurrent GBM. Re-resection is recommended, if possible, to improve symptoms and decrease tumor volume. However, this treatment option is possible only in a minority of patients, and for these patients re-irradiation has emerged as a possible treatment.
- Modern radiation therapy (RT) techniques allow delivery of re-irradiation while minimizing the dose to previously treated organs at risk (OAR) within the radiation field.
- Data from a recently completed clinical trial at our center (16-C-0081, NCT02709226) suggests that the Maximum Tolerated Dose (MTD) of re-irradiation in 350 cGy fractions is 4200 cGy.
Objective:
-To determine the maximum tolerated dosage of daily re-irradiation in participants with recurrent Grade 4 gliomas
Eligibility:
- A histologic diagnosis of GBM, gliosarcoma, or transformation, from a lower grade to a grade 4 brain tumor.
- Previous glioma irradiation to curative-intent doses.
- Age >= 18.
- Karnofsky performance scale (KPS) >= 70.
Design:
- This is a single center phase I trial using a '3 + 3' design and a three (3) dose level hypofractionation schema to enroll a maximum of 21 evaluable participants.
- Prior to radiation therapy, participants will undergo laboratory evaluations, magnetic resonance imaging (MRI), and a treatment planning computed tomography (CT).
- RT will be administered daily 4 days a week for 1, 2, or 3 weeks in the Radiation Oncology Branch, NCI, at NIH. Radiation will be delivered on consecutive days, 4 fractions per week via a linear accelerator using 6 megavoltage (MV) photons or greater.
- Follow-up visits following RT are planned at 1 month, every 2 months for years 1-2, and every 3 months for year 3. These visits will be stopped earlier in case of progression. After progression or 3 years of follow-up, participants will be followed remotely for survival until 5 years after treatment completion.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1/Arm 1 | Experimental | Radiation: Radiation TherapyFraction size escalation of 3 planned re-irradiation dose levels. |
| 2/Arm 2 | Experimental | Radiation: Radiation TherapyMTD of re-irradiation dose. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histologic diagnosis of primary glioblastoma or gliosarcoma of the brain, or secondary glioblastoma of the brain due to transformation from a lower grade to a grade 4 tumor.
- Age >= 18.
- KPS >= 70%.
- Previous tumor irradiation to curative-intent doses.
- Radiation dose constraints must be achievable based on assessment with MRI and treatment planning CT.
Key exclusion criteria (12 listed)
- Recent systemic therapy prior to the initiation of the study therapy as follows:
- Participants who are unable to undergo MRI evaluation or receive gadolinium contrast for any reason.
- Any prior therapy after surgical re-resection or biopsy within 2 weeks prior to the initiation of the study therapy.
- Requiring radiation therapy within 12 months prior to the initiation of study therapy.
- History of prior therapy with Novacure TTF, Gliadel wafers, or GammaTile therapy.
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 |
|---|---|---|
| Radiation TherapyRadiation therapy will be administered via a linear accelerator using 6 megavoltage (MV) photons or greater. | Radiation | 1/Arm 1, 2/Arm 2 |
Primary outcome
MTD of daily re-irradiation in participants with recurrent grade 4 gliomas
Time frame: DLT period (28 days)
The number of participants experiencing DLTs within the DLT period will be reported for each hypofractionation schema. The MTD will be identified, and the proportion of participants treated with the MTD experiencing DLT will be reported.
6 secondary outcomes
Progression free survival
Time frame: Baseline, 30 day safety follow up visit, every 2 months for 2 years, every 3 months for 3rd year, or until progression
Overall survival
Time frame: Treatment and follow up
Compliance and feasibility of administering PRO in this participant population
Time frame: Baseline through 3 years post radiation therapy.
Tolerability of treatment by assessing adverse events, cognitive function, physical function, and side effect bother
Time frame: First radiation treatment administration through 6 months after the last day of radiation. Beyond 6 months after radiation, only adverse events which are serious and related to radiation need to be recorded.
Longitudinally describe and evaluate disease and treatment-related symptom severity and interference with daily activities
Time frame: Baseline through 3 years post radiation therapy.
Meaningful change in disease and treatment-related symptoms by using anchors
Time frame: Baseline through 3 years post radiation therapy.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All IPD recorded in the medical record will be shared with intramural investigators upon request. This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review.
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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.
Peter GK Mathen, M.D. principal investigator
National Cancer Institute (NCI)
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 Radiation Therapy in people with Astrocytoma and Glioma, run by National Cancer Institute (NCI) 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 11 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 16 Oct 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rukayat O Salau ((240) 858-3712, rukayat.salau@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MTD of daily re-irradiation in participants with recurrent grade 4 gliomas (time frame: DLT period (28 days)). 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 16 Oct 2026.