Astrocytoma, Grade IVPhase 1NCT02709226
Dose Escalation Trial of Re-irradiation in Good Prognosis Recurrent Glioblastoma
A Phase 1 study testing Radiation in people with Astrocytoma, Grade IV and Giant Cell Glioblastoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: A glioblastoma is a tumor in the brain. It is treated with surgery, chemotherapy and radiation therapy. However, most people s tumors come back after therapy. When the tumor grows back, surgery or chemotherapy may not be possible or may no longer work. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Astrocytoma, Grade IV, Giant Cell Glioblastoma, Glioblastoma Multiforme
- What is being tested?
- Radiation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jun 2016to 19 Jul 2023
- Phase
- Phase 1
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological diagnosis
- Previous histologic diagnosis of glioblastoma, transformation to glioblastoma or gliosarcoma established by biopsy or resection prior to enrollment as evident on NIH or outside pathology.
- Patients must be age greater than or equal to 18.
- Patients should have a KPS greater than or equal to 70%
- Prior standard radiation therapy to a dose ranging from 50 to 60 Gy at 1.8 to 2 Gy per fraction.
- Patients must be more than or equal to 14 days from previous cytotoxic treatment.
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- Concurrent therapy
- The concurrent use of bevacizumab is allowed if previously initiated for tumor progression or symptomatic management. Prior temozolomide or other cytotoxic chemotherapy is allowed.
- Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
Who cannot join
- Prior therapy < than 2 weeks since surgical re-resection or biopsy
- Pregnant or breast feeding females are excluded due to potential mutagenic effects on the developing fetus or newborn
- Preexisting grade 3 or 4 nervous system disorder as per CTCAE Version 4.0
- Clinically significant unrelated systemic illness (including but not limited to active life threatening infection, cardiac or neurologic events, current hospital admission for a coexisting comorbid illness), which would make it impossible for the patient to tolerate re-irradiation or systemic chemotherapy or likely to interfere with the results.
- Patients exhibiting baseline grade 3 or 4 by CTCAE criteria are excluded due to difficulty in assigning these to the study intervention as treatment related DLT.
- Patients with preexisting known or suspected radiation sensitivity syndromes will be excluded due to potential confounding effect on outcome.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: A Phase I Dose Escalation Trial of Re-Irradiation in Good Prognosis Recurrent Glioblastoma
Background:
A glioblastoma is a tumor in the brain. It is treated with surgery, chemotherapy and radiation therapy. However, most people s tumors come back after therapy. When the tumor grows back, surgery or chemotherapy may not be possible or may no longer work. Repeat radiation therapy or re-irradiation, is an option for treating these tumors when they regrow.
Read more
Objective:
To find out the safety and highest tolerated dose of re-irradiation for people who have recurrent glioblastoma.
Eligibility:
People ages 18 50 who have glioblastoma that has been treated with radiation but has regrown.
Design:
Participants will be screened with:
Medical history
Physical exam
MRI of the brain: They will lie in a machine that takes pictures of the brain.
Participants will have baseline tests before they start therapy. These will include:
Blood tests
Neuropsychological tests: These test things like memory, attention, and thinking.
Quality of life questionnaire
Eye and hearing tests
Participants will get a CT of the brain prior to radiation start in order to plan the radiation treatment. Once the plan is completed, they will receive radiation once a day Monday Friday for a total of 10 17 treatments. They will lie on their back for about 10 minutes while they get the treatment.
Participants will be monitored for side effects.
After they finish treatment, participants will have visits 1, 2, and 3 months later. Then they will have them every 2 months for 3 years. These will include:
Medical history
Physical exam
Blood tests
MRI of the brain.
Quality of life questionnaire
Neuropsychological tests (at some visits)
After 3 years, participants will be contacted by phone each month.
Read the detailed description
Background
- Although the survival of gliomas has improved, most high grade gliomas will recur in field or adjacent to the treatment field within months to years of the original treatment. In newly diagnosed GBM, the concurrent use of radiation and temozolomide is standard of care.
- Surgical resection upon recurrence is possible in less than 50% of patients. For a significant proportion of recurrent glioma patients in whom reresection is not favourable and for whom systemic options have been exhausted, re-irradiation has emerged as a possible treatment option.
- Using modern precision RT techniques (stereotactic radiosurgery (SRS), stereotactic radiotherapy (SRT) or intensity modulated radiation therapy (IMRT), Rapid Arc techniques), re-irradiation has proven a feasible option with possible benefit in outcome as these techniques are often able to minimize dose to previously treated organs at risk in the field (OAR) and treat the recurrence safely.
- Data from multiple retrospective studies has indicated that not only is re-irradiation feasible, but it may actually improve survival in the appropriately selected patient.
Objective
The primary objective of this phase I study is to determine maximum tolerated re-irradiation dose (MTD).
Eligibility
- Recurrent glioblastoma or gliosarcoma
- Prior standard radiation therapy to a dose ranging from 50 to 60 Gy at 1.8 to 2 Gy per fraction.
- Prior irradiation > 12 months from enrollment on protocol.
- Age greater than or equal to 18.
- KPS greater than or equal to 70
Design
- Radiation therapy will be administered daily Monday-Friday at Radiation Oncology Branch (ROB), NCI. All the protocol related follow-up appointments will occur at NCI ROB. Radiation therapy dose will be administered on consecutive treatment days, 5 fractions per week via a linear accelerator using 6 MV photons or greater. Using a 3 plus 3 design , and three dose escalation levels, with 6 patients per dose level with 9 total patients at the MTD (provided no DLT), a maximum of 21 evaluable patients will be enrolled.
- Time to progression will be determined by the interval from initiation of treatment on protocol to progression as per RANO criteria.
- Neurologic decline without radiographic evidence of tumor will be designated as treatment related toxicity. Survival duration will be determined by the interval from initiation of treatment on protocol to date of death.
- Being tested
- Radiation
- Keywords
- Brain Tumor, Astrocytoma, GBM, Radiation Therapy
- Medical subject headings
- Glioblastoma, Gliosarcoma, Brain Neoplasms, Astrocytoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RadiationRadiation
Radiation therapy will be administered daily Monday-Friday at NCI, ROB unless the treatment schedule requires amendment in the event of inclement weather or federal holidays. Radiation therapy dose will be administered as per on consecutive treatment days, 5 fractions per week via a linear accelerator using 6 MV photons or greater. Dose escalation is as follows: dose level 1 (DL1) 3.5 Gy x 10; dose level 2 (DL2) 3.5 Gy x 12; dose level 3 (DL3) 3.5 Gy x 14. If 2 DLTs are observed in the second dose level a step down dose of 3.0 Gy x 14 fractions will be tested. If 2 DLTs are observed in the third dose level a step down dose of 3.0 Gy x 17 fractions will be tested. The study will have 3 planned re-irradiation dose levels, with 1 to 6 patients per dose level using the 3+3 design to define the MTD. The number of patients may be increased to 9 total patients at the MTD ( provided no DLT) with a maximum of 21 evaluable patients enrolled.
| Study group | Role | What they receive |
|---|---|---|
| 1/Radiation | Experimental | Dose escalation is as follows: dose level 1 (DL1) 3.5 Gy x 10; dose level 2 (DL2) 3.5 Gy x 12; dose level 3 (DL3) 3.5 Gy x 14. If 2 DLTs are observed in the second dose level a step down dose of 3.0 Gy x 14 fractions will be tested. If 2 DLTs are observed in the third dose level a step down dose of 3.0 Gy x 17 fractions will be tested. The study will have 3 planned re-irradiation dose levels, with 1 to 6 patients per dose level using the 3+3 design to define the MTD. The number of patients may be increased to 9 total patients at the MTD ( provided no DLT) with a maximum of 21 evaluable patients enrolled. Receives: Radiation: Radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine maximum tolerated re-irradiation dose (MTD).
The MTD will be based on the assessment of DLT within one month following the re-irradiation, and will be defined as the dose level at which less than one-third of patients (0/3 or 0-1/6 patients) treated at that dose experience a DLT, with the next higher dose level demonstrating a one-third or greater number of patients (>= 2/3 or >= 2/6 patients) having DLT.
Measured: 1 month after completion of re-irradiation
Secondary outcomes (3)
To determine QOL and impact on neurocognition in the setting of re-irradiation of recurrent glioblastoma
QOL scores will be summarized at baseline and for each visit. Changes from baseline of health-related quality of life questionnaire mean scores will be evaluated
Measured: baseline and at each visit
To determine progression free survival and overall survival.
interval from initiation of treatment on protocol to progression as per RANO criteria Survival duration will be determined by the interval from initiation of treatment on protocol to date of death
Measured: time of progression; time of death
To determine late toxicity secondary to re-irradiation
listing of adverse events
Measured: completion of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2016 (estimated)
- Study start15 Jun 2016
- Primary completion16 Dec 2022
- Study completion19 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Astrocytoma, Grade IVStudies 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
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Kevin A Camphausen, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02709226
- Sponsor's protocol ID
- 160081
- Other IDs
- 16-C-0081
- Status last verified
- 16 Dec 2025
- First submitted
- 15 Mar 2016
- Last updated
- 31 Dec 2025
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Escalation Trial of Re-Irradiation in Good Prognosis Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT02709226
- Acronym / sponsor ID
- 160081
- Keywords
- Brain Tumor, Astrocytoma, GBM, Radiation Therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 15 Jun 2016 (actual)
- Primary completion
- 16 Dec 2022 (actual)
- Study completion
- 19 Jul 2023 (actual)
- First posted
- 16 Mar 2016 (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.
Background:
A glioblastoma is a tumor in the brain. It is treated with surgery, chemotherapy and radiation therapy. However, most people s tumors come back after therapy. When the tumor grows back, surgery or chemotherapy may not be possible or may no longer work. Repeat radiation therapy or re-irradiation, is an option for treating these tumors when they regrow.
Objective:
To find out the safety and highest tolerated dose of re-irradiation for people who have recurrent glioblastoma.
Eligibility:
People ages 18 50 who have glioblastoma that has been treated with radiation but has regrown.
Design:
Participants will be screened with:
Medical history
Physical exam
MRI of the brain: They will lie in a machine that takes pictures of the brain.
Participants will have baseline tests before they start therapy. These will include:
Blood tests
Neuropsychological tests: These test things like memory, attention, and thinking.
Quality of life questionnaire
Eye and hearing tests
Participants will get a CT of the brain prior to radiation start in order to plan the radiation treatment. Once the plan is completed, they will receive radiation once a day Monday Friday for a total of 10 17 treatments. They will lie on their back for about 10 minutes while they get the treatment.
Participants will be monitored for side effects.
After they finish treatment, participants will have visits 1, 2, and 3 months later. Then they will have them every 2 months for 3 years. These will include:
Medical history
Physical exam
Blood tests
MRI of the brain.
Quality of life questionnaire
Neuropsychological tests (at some visits)
After 3 years, participants will be contacted by phone each month.
Detailed description
Background
- Although the survival of gliomas has improved, most high grade gliomas will recur in field or adjacent to the treatment field within months to years of the original treatment. In newly diagnosed GBM, the concurrent use of radiation and temozolomide is standard of care.
- Surgical resection upon recurrence is possible in less than 50% of patients. For a significant proportion of recurrent glioma patients in whom reresection is not favourable and for whom systemic options have been exhausted, re-irradiation has emerged as a possible treatment option.
- Using modern precision RT techniques (stereotactic radiosurgery (SRS), stereotactic radiotherapy (SRT) or intensity modulated radiation therapy (IMRT), Rapid Arc techniques), re-irradiation has proven a feasible option with possible benefit in outcome as these techniques are often able to minimize dose to previously treated organs at risk in the field (OAR) and treat the recurrence safely.
- Data from multiple retrospective studies has indicated that not only is re-irradiation feasible, but it may actually improve survival in the appropriately selected patient.
Objective
The primary objective of this phase I study is to determine maximum tolerated re-irradiation dose (MTD).
Eligibility
- Recurrent glioblastoma or gliosarcoma
- Prior standard radiation therapy to a dose ranging from 50 to 60 Gy at 1.8 to 2 Gy per fraction.
- Prior irradiation > 12 months from enrollment on protocol.
- Age greater than or equal to 18.
- KPS greater than or equal to 70
Design
- Radiation therapy will be administered daily Monday-Friday at Radiation Oncology Branch (ROB), NCI. All the protocol related follow-up appointments will occur at NCI ROB. Radiation therapy dose will be administered on consecutive treatment days, 5 fractions per week via a linear accelerator using 6 MV photons or greater. Using a 3 plus 3 design , and three dose escalation levels, with 6 patients per dose level with 9 total patients at the MTD (provided no DLT), a maximum of 21 evaluable patients will be enrolled.
- Time to progression will be determined by the interval from initiation of treatment on protocol to progression as per RANO criteria.
- Neurologic decline without radiographic evidence of tumor will be designated as treatment related toxicity. Survival duration will be determined by the interval from initiation of treatment on protocol to date of death.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1/Radiation | Experimental | Radiation: RadiationDose escalation is as follows: dose level 1 (DL1) 3.5 Gy x 10; dose level 2 (DL2) 3.5 Gy x 12; dose level 3 (DL3) 3.5 Gy x 14. If 2 DLTs are observed in the second dose level a step down dose of 3.0 Gy x 14 fractions will be tested. If 2 DLTs are observed in the third dose level a step down dose of 3.0 Gy x 17 fractions will be tested. The study will have 3 planned re-irradiation dose levels, with 1 to 6 patients per dose level using the 3+3 design to define the MTD. The number of patients may be increased to 9 total patients at the MTD ( provided no DLT) with a maximum of 21 evaluable patients enrolled. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Previous histologic diagnosis of glioblastoma, transformation to glioblastoma or gliosarcoma established by biopsy or resection prior to enrollment as evident on NIH or outside pathology.
- The concurrent use of bevacizumab is allowed if previously initiated for tumor progression or symptomatic management. Prior temozolomide or other cytotoxic chemotherapy is allowed.
Key exclusion criteria (6 listed)
- Prior therapy < than 2 weeks since surgical re-resection or biopsy
- Pregnant or breast feeding females are excluded due to potential mutagenic effects on the developing fetus or newborn
- Preexisting grade 3 or 4 nervous system disorder as per CTCAE Version 4.0
- Clinically significant unrelated systemic illness (including but not limited to active life threatening infection, cardiac or neurologic events, current hospital admission for a coexisting comorbid illness), which would make it impossible for the patient to tolerate re-irradiation or systemic chemotherapy or likely to interfere with the results.
- Patients exhibiting baseline grade 3 or 4 by CTCAE criteria are excluded due to difficulty in assigning these to the study intervention as treatment related DLT.
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 |
|---|---|---|
| RadiationRadiation therapy will be administered daily Monday-Friday at NCI, ROB unless the treatment schedule requires amendment in the event of inclement weather or federal holidays. Radiation therapy dose will be administered as per on consecutive treatment days, 5 fractions per week via a linear accelerator using 6 MV photons or greater. Dose escalation is as follows: dose level 1 (DL1) 3.5 Gy x 10; dose level 2 (DL2) 3.5 Gy x 12; dose level 3 (DL3) 3.5 Gy x 14. If 2 DLTs are observed in the second dose level a step down dose of 3.0 Gy x 14 fractions will be tested. If 2 DLTs are observed in the third dose level a step down dose of 3.0 Gy x 17 fractions will be tested. The study will have 3 planned re-irradiation dose levels, with 1 to 6 patients per dose level using the 3+3 design to define the MTD. The number of patients may be increased to 9 total patients at the MTD ( provided no DLT) with a maximum of 21 evaluable patients enrolled. | Radiation | 1/Radiation |
Primary outcome
To determine maximum tolerated re-irradiation dose (MTD).
Time frame: 1 month after completion of re-irradiation
The MTD will be based on the assessment of DLT within one month following the re-irradiation, and will be defined as the dose level at which less than one-third of patients (0/3 or 0-1/6 patients) treated at that dose experience a DLT, with the next higher dose level demonstrating a one-third or greater number of patients (>= 2/3 or >= 2/6 patients) having DLT.
3 secondary outcomes
To determine QOL and impact on neurocognition in the setting of re-irradiation of recurrent glioblastoma
Time frame: baseline and at each visit
To determine progression free survival and overall survival.
Time frame: time of progression; time of death
To determine late toxicity secondary to re-irradiation
Time frame: completion of study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2025.
- 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.
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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.
Kevin A Camphausen, 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 in people with Astrocytoma, Grade IV and Giant Cell Glioblastoma, 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 10 inclusion and 6 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 31 Dec 2025. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine maximum tolerated re-irradiation dose (MTD). (time frame: 1 month after completion of re-irradiation). 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 31 Dec 2025.