GlioblastomaPhase 1/2NCT04019262
Short Course Chemo-Radiation Therapy for Patients With Newly Diagnosed Glioblastoma
A Phase 1/2 study testing Radiation Therapy and Temozolomide Oral Product in people with Glioblastoma, run by John Flickinger at 1 site in United States.
Trial summary
This is a prospective, randomized, open-label, exploratory trial of temozolomide-based chemo-radiotherapy which compares two widely used established radiation schedules with either 40 Gy in 15 fractions or 25 Gy in 5 fractions with concurrent temozolomide for both schedules in patients with glioblastoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Radiation Therapy and Temozolomide Oral Product
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Dec 2021to Jul 2027
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Each patient must meet all of the following inclusion criteria for study enrollment:
- Age ≥18 with ability to provide written informed consent
- Pathologically confirmed WHO Grade IV Gliobastoma prior receiving radiotherapy
- Prior radiotherapy to a dose of ≥50Gy
- No signs of distant metastases
- Baseline laboratory assessment including CBC and blood chemistry, ANC > or equal 1500, Platelet count greater or equal 100. Liver function tests and creatinine not greater than twice ULN.
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- Patient should not be pregnant. Urine or blood β-HCG within 14 days prior to study start for females who are not atleast one year post-menopausal or who have ot undergone a surgical sterilization procedure
- A baseline MRI scan of the brain is required to determine how much tumor is present for properly planning patient's radiotherapy.
- Karnofsky Performance Status (KPS) below 60 or ECOG of 3 or 4
- Any number or type of prior chemotherapy is allowed (patient may receive concurrent or adjuvant systemic therapy such as cetuximab at the discretion of the treating oncologic team).
Who cannot join
- Patients meeting any of the following exclusion criteria are not eligible for enrollment:
- Evidence of distant metastases on any staging or imaging modality
- Women who are breast feeding, or have a positive pregnancy test (reproductive age should use effective birth control during study)
- Any co-morbidity or condition of sufficient severity to limit full compliance with the protocol per assessment by the principal investigator.
- Karnofsky Performance Status less than 50
- Prior radiotherapy to involved site in brain.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh Medical Center, Radiation Oncology
Pittsburgh, Pennsylvania, 15232
About this study
Official title: Short Course Chemo-Radiation Therapy for Patients With Newly Diagnosed Glioblastoma: Comparison of Two Established Schedules
This is a prospective, randomized, open-label, exploratory trial of temozolomide-based chemo-radiotherapy which compares two widely used established radiation schedules with either 40 Gy in 15 fractions or 25 Gy in 5 fractions with concurrent temozolomide for both schedules in patients with glioblastoma.
Read the detailed description
All patients in the study will receive usual care with short-course radiotherapy (RT) and TMZ-chemo pills.
There are three phases of treatment in this study: the Chemo-radiation Phase, the Adjuvant Phase, and the Follow-Up Phase.
Twenty-eight or fewer days prior to starting the Chemo-radiation Phase, patients will have a baseline Magnetic Resonance Imaging (MRI) scan.
Chemo-radiation Phase: In this, patient will be assigned to either a one week or a three week treatment group with radiation treatments given approximately 5 days a week as directed by the study doctor. During this time they will also take TMZ-chemo orally (by mouth) once a day on every evening including weekends starting the evening of the day that you start radiotherapy. Once radiation is completed, you will stop taking TMZ-chemo for approximately 4 weeks before going to the next phase.
Radiation therapy: Patients will be randomized between standard radiation treatment at UPMC Radiation Oncology facilities included in this protocol with either 40 Gy in 15 fractions or 25 Gy in 5 fractions, using 6 to 23 MV x-rays along with concurrent temozolomide chemotherapy for both treatment schedules.
- Clinical treatment volumes (CTV) will include all contrast enhancing tumor plus 1.7cm expansion into brain tissue (not crossing the tentorium) and all T2 FLAIR hyperintensity plus 7mm expansion into brain tissue (not crossing the tentorium). A planning target volume (PTV) expansion of 3mm will be then added to the CTV. No additional exclusion of brainstem or optic nerves is required as both treatment schedules are within tolerance.
- Treatment may be delivered with either 3D-conformal or intensity modulated radiotherapy (IMRT) techniques.
Adjuvant Phase: In the Adjuvant Phase, you will receive standard monthly 5 day cycles of TMZ-chemo at 150 mg/m^2 per day for up to 1 year.
Chemotherapy: Patient will receive concurrent temozolomide throughout radiation therapy, followed by standard monthly 5 day cycles for up to 1 year. Patients randomized to 25 Gy in 5 fractions will receive 150 mg/m^2 of temozolomide per day for 5 days starting first day of radiotherapy. Patients randomized to 40 Gy in 15 fractions will receive 75 mg/m2 of temozolomide per day for 19 days starting first day of radiotherapy. Patients will be appropriately pre-medicated with anti-nausea medication, prior to taking temozolomide. All patients will also receive prophylactic treatment for pneumocystis pneumonia with Bactrim or other alternative antibiotics if allergic.
Follow-up Interval: Procedures performed to evaluate the safety and effectiveness of the study procedures are called "monitoring" or "follow-up" procedures. Subject participants will not be scheduled for any additional follow-up visits for this study than they would normally have if they were not in this study. Radiation Oncologists and Neuro-Oncologists usually see their patients one month after the first chemo-radiotherapy cycle before starting the next cycle of chemotherapy. After that Neuro-Oncologists and Radiation Oncologists will see the patients every 1-3 months.
- Conditions
- Glioblastoma
- Being tested
- Radiation Therapy, Temozolomide Oral Product
- Keywords
- Chemo-Radiation Therapy, temozolomide, lymphocytopenia
- Medical subject headings
- Glioblastoma, Lymphopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radiation TherapyRadiation
Radiation
Temozolomide Oral ProductDrug
Oral Temozolomide (150mg/m^2 or 75 mg/m^2)
| Study group | Role | What they receive |
|---|---|---|
| 40 Gy in 15 fractions | Active comparator | Patients randomized to 40 Gy in 15 fractions will receive 75 mg/m^2 temozolomide per day for 15 days starting the first day of radiotherapy. This treatment will be followed by standard monthly 5 day cycles at 150 mg/m^2 for upto 1 year. Receives: Radiation: Radiation Therapy; Drug: Temozolomide Oral Product |
| 25 Gy in 5 fractions | Active comparator | Patients randomized to 25 Gy in 5 fractions will receive 150 mg/m^2 temozolomide per day for 5 days starting the first day of radiotherapy. This treatment will be followed by standard monthly 5 day cycles at 150 mg/m^2 for upto 1 year. Receives: Radiation: Radiation Therapy; Drug: Temozolomide Oral Product |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival (OS)
The length of time from the start of treatment that patients remain alive.
Measured: Up to 9 years
Change in Absolute Lymphocyte Count
Differences in absolute lymphocyte count (total lymphocyte count <800 - 500/mm^3 <0.8 - 0.5 x 10^9 /L) / total # patients, during treatment.
Measured: From baseline up to 5 years.
Secondary outcomes (2)
Progression free survival (PFS) - 25 Gy in 5 fractions
The length of time during and after the treatment that a patient lives without worsening disease per Response Assessment in Neuro-Oncology (RANO) criteria. Disease progression per RANO: (any of the following): ≥25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement obtained either at baseline (if no decrease) or best response, on stable or increasing doses of corticosteroids*; significant increase in T2/FLAIR nonenhancing lesion on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy* not caused by comorbid events; any new lesion; clear clinical deterioration not attributable to other causes apart from the tumor (eg, seizures, medication adverse effects) or changes in corticosteroid dose; failure to return for evaluation as a result of death or deteriorating condition; or clear progression of nonmeasurable disease.
Measured: Up to 9 years
Progression free survival (PFS) - 40 Gy in 15 fractions
The length of time during and after the treatment that a patient lives without worsening disease per Response Assessment in Neuro-Oncology (RANO) criteria. Disease progression per RANO: (any of the following): ≥25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement obtained either at baseline (if no decrease) or best response, on stable or increasing doses of corticosteroids*; significant increase in T2/FLAIR nonenhancing lesion on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy* not caused by comorbid events; any new lesion; clear clinical deterioration not attributable to other causes apart from the tumor (eg, seizures, medication adverse effects) or changes in corticosteroid dose; failure to return for evaluation as a result of death or deteriorating condition; or clear progression of nonmeasurable disease.
Measured: Up to 9 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2019
- Study start14 Dec 2021
- Primary completionDec 2026 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- John Flickinger
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, John Flickinger, University of Pittsburgh
- Investigators
- John Flickinger, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04019262
- Sponsor's protocol ID
- HCC 19-022
- Status last verified
- Jun 2025
- First submitted
- 11 Jul 2019
- Last updated
- 18 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short Course Chemo-Radiation Therapy for Patients With Newly Diagnosed Glioblastoma: Comparison of Two Established Schedules
- ClinicalTrials.gov ID
- NCT04019262
- Acronym / sponsor ID
- HCC 19-022
- Conditions
- Glioblastoma
- Keywords
- Chemo-Radiation Therapy, temozolomide, lymphocytopenia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 2 participants (actual)
- Lead sponsor
- John FlickingerUniversity, hospital or other
- Study start
- 14 Dec 2021 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 15 Jul 2019 (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.
This is a prospective, randomized, open-label, exploratory trial of temozolomide-based chemo-radiotherapy which compares two widely used established radiation schedules with either 40 Gy in 15 fractions or 25 Gy in 5 fractions with concurrent temozolomide for both schedules in patients with glioblastoma.
Detailed description
All patients in the study will receive usual care with short-course radiotherapy (RT) and TMZ-chemo pills.
There are three phases of treatment in this study: the Chemo-radiation Phase, the Adjuvant Phase, and the Follow-Up Phase.
Twenty-eight or fewer days prior to starting the Chemo-radiation Phase, patients will have a baseline Magnetic Resonance Imaging (MRI) scan.
Chemo-radiation Phase: In this, patient will be assigned to either a one week or a three week treatment group with radiation treatments given approximately 5 days a week as directed by the study doctor. During this time they will also take TMZ-chemo orally (by mouth) once a day on every evening including weekends starting the evening of the day that you start radiotherapy. Once radiation is completed, you will stop taking TMZ-chemo for approximately 4 weeks before going to the next phase.
Radiation therapy: Patients will be randomized between standard radiation treatment at UPMC Radiation Oncology facilities included in this protocol with either 40 Gy in 15 fractions or 25 Gy in 5 fractions, using 6 to 23 MV x-rays along with concurrent temozolomide chemotherapy for both treatment schedules.
- Clinical treatment volumes (CTV) will include all contrast enhancing tumor plus 1.7cm expansion into brain tissue (not crossing the tentorium) and all T2 FLAIR hyperintensity plus 7mm expansion into brain tissue (not crossing the tentorium). A planning target volume (PTV) expansion of 3mm will be then added to the CTV. No additional exclusion of brainstem or optic nerves is required as both treatment schedules are within tolerance.
- Treatment may be delivered with either 3D-conformal or intensity modulated radiotherapy (IMRT) techniques.
Adjuvant Phase: In the Adjuvant Phase, you will receive standard monthly 5 day cycles of TMZ-chemo at 150 mg/m^2 per day for up to 1 year.
Chemotherapy: Patient will receive concurrent temozolomide throughout radiation therapy, followed by standard monthly 5 day cycles for up to 1 year. Patients randomized to 25 Gy in 5 fractions will receive 150 mg/m^2 of temozolomide per day for 5 days starting first day of radiotherapy. Patients randomized to 40 Gy in 15 fractions will receive 75 mg/m2 of temozolomide per day for 19 days starting first day of radiotherapy. Patients will be appropriately pre-medicated with anti-nausea medication, prior to taking temozolomide. All patients will also receive prophylactic treatment for pneumocystis pneumonia with Bactrim or other alternative antibiotics if allergic.
Follow-up Interval: Procedures performed to evaluate the safety and effectiveness of the study procedures are called "monitoring" or "follow-up" procedures. Subject participants will not be scheduled for any additional follow-up visits for this study than they would normally have if they were not in this study. Radiation Oncologists and Neuro-Oncologists usually see their patients one month after the first chemo-radiotherapy cycle before starting the next cycle of chemotherapy. After that Neuro-Oncologists and Radiation Oncologists will see the patients every 1-3 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 40 Gy in 15 fractions | Active comparator | Radiation: Radiation Therapy, Drug: Temozolomide Oral ProductPatients randomized to 40 Gy in 15 fractions will receive 75 mg/m^2 temozolomide per day for 15 days starting the first day of radiotherapy. This treatment will be followed by standard monthly 5 day cycles at 150 mg/m^2 for upto 1 year. |
| 25 Gy in 5 fractions | Active comparator | Radiation: Radiation Therapy, Drug: Temozolomide Oral ProductPatients randomized to 25 Gy in 5 fractions will receive 150 mg/m^2 temozolomide per day for 5 days starting the first day of radiotherapy. This treatment will be followed by standard monthly 5 day cycles at 150 mg/m^2 for upto 1 year. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age ≥18 with ability to provide written informed consent
- Pathologically confirmed WHO Grade IV Gliobastoma prior receiving radiotherapy
- Prior radiotherapy to a dose of ≥50Gy
- No signs of distant metastases
- Baseline laboratory assessment including CBC and blood chemistry, ANC > or equal 1500, Platelet count greater or equal 100. Liver function tests and creatinine not greater than twice ULN.
Key exclusion criteria (6 listed)
- Evidence of distant metastases on any staging or imaging modality
- Women who are breast feeding, or have a positive pregnancy test (reproductive age should use effective birth control during study)
- Any co-morbidity or condition of sufficient severity to limit full compliance with the protocol per assessment by the principal investigator.
- Karnofsky Performance Status less than 50
- Prior radiotherapy to involved site in brain.
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 | Radiation | 25 Gy in 5 fractions, 40 Gy in 15 fractions |
| Temozolomide Oral ProductOral Temozolomide (150mg/m^2 or 75 mg/m^2) | Drug | 25 Gy in 5 fractions, 40 Gy in 15 fractions |
Primary outcome
Overall survival (OS)
Time frame: Up to 9 years
The length of time from the start of treatment that patients remain alive.
Change in Absolute Lymphocyte Count
Time frame: From baseline up to 5 years.
Differences in absolute lymphocyte count (total lymphocyte count <800 - 500/mm^3 <0.8 - 0.5 x 10^9 /L) / total # patients, during treatment.
2 secondary outcomes
Progression free survival (PFS) - 25 Gy in 5 fractions
Time frame: Up to 9 years
Progression free survival (PFS) - 40 Gy in 15 fractions
Time frame: Up to 9 years
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 18 Jun 2025.
- Individual participant dataSharing planned: No
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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.
John Flickinger, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Radiation Therapy and Temozolomide Oral Product in people with Glioblastoma, run by John Flickinger 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: under way, not looking for participants, as of the sponsor's last update on 18 Jun 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 combined 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.
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?
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?
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?
Overall survival (OS) (time frame: Up to 9 years). 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 18 Jun 2025.