GlioblastomaPhase 2GlioCave/NOA17NCT02715297
Adjuvant Stereotactic Fractionated Radiotherapy to the Resection Cavity in Recurrent Glioblastoma
A Phase 2 study testing SRT to the resection cavity in people with Glioblastoma, run by Technical University of Munich at 1 site in Germany.
Trial summary
This multi-center randomized controlled phase II trial will investigate the impact of stereotactic fractionated radiotherapy to the resection cavity of complete resected recurrent glioblastoma on progression free survival. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Glioblastoma
- What is being tested?
- SRT to the resection cavity
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 162 participants
- Where
- 1 siteGermany
- Study dates
- Feb 2016to Feb 2023
- Phase
- Phase 2
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Unifocal, supratentorial recurrent glioblastoma
- Prior course of standard treatment
- Complete resection of all contrast enhancing areas
- age ≥ 18 years of age
- Karnofsky Performance Score 60% or higher
- For women with childbearing potential, (and men) adequate contraception.
- Ability of subject to understand character and individual consequences of the clinical trial
- Written informed consent (must be available before enrolment in the trial)
Who cannot join
- Multifocal glioblastoma of gliomatosis cerebri
- Time interval of less than 6 months after primary radiotherapy
- Previous re-irradiation or prior radiosurgery of prior treatment with interstitial radioactive seeds
- refusal of the patients to take part in the study
- Patients who have not yet recovered from acute toxicities of prior therapies
- Known carcinoma < 5 years ago (excluding Carcinoma in situ of the cervix, basal cell carcinoma, squamous cell carcinoma of the skin) requiring immediate treatment interfering with study therapy
- Pregnant or lactating women
- Participation in another clinical study or observation period of competing trials, respectively.
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
Dept. Radiation Oncology
Munich, Bavaria, 81675
Stephanie E. Combs, Prof. Dr., 089 4140 4501, direktion.radonk@mri.tum.de
Christoph Straube, Dr.
About this study
This multi-center randomized controlled phase II trial will investigate the impact of stereotactic fractionated radiotherapy to the resection cavity of complete resected recurrent glioblastoma on progression free survival. As secondary endpoints, overall survival, safety and toxicity as well as early response criteria on MRI, quality of life and neurocognitive function will be assessed. Chemotherapy will not be part of the protocol, however, additional treatment will be possible upon investigators best choice.
Read the detailed description
The treatment of recurrent glioblastoma is, beside of its abundance in clinical practice, still under discussion. Patients presenting with recurrent disease are therefore treated within individual concepts, largely based on small prospective trials, retrospective evaluations or case reports. Therefore, the treatment ranges from best supportive care over primary systemic treatments towards local therapies such as radiotherapy or surgical resection. Even if there might be a large selection bias, local therapies with or without concomitant or adjuvant chemotherapy seem to promise the largest prognostic benefit. Whether the combination of surgical resection and adjuvant radiotherapy improves survival, as it does within the primary situation, is unknown.
The result of surgical resection might have an impact as well. Several case reports, retrospective evaluations and prospective studies have also included patients with remaining gross tumor after maximum save resection. In these trials, radiotherapy was associated with improvements in progression free as well as overall survival. Therefore, the influence of neuroimaging on prognosis is currently evaluated within the GLIA-A trial. Furthermore, stereotactic radiotherapy with or without an experimental systemic therapy is currently investigated within another multicenter randomized trial (NOA-12).
Whether patients might benefit from a postoperative radiotherapy of the resection cavity after complete extirpation of all macroscopic tumor is key question of this protocol.
To answer this question, the considered standard of care after complete resection, namely observation with or without adjuvant systemic therapy, will be compared to a postoperative normofractionated stereotactic radiotherapy towards the resection cavity within an open label, randomized trial. The prescribed total dose will be 46 Gy in 2 Gy fractions of 36 Gy in 3 Gy fractions depending on the treatment volume.
Concerning safety, side effects will be monitored prospectively. Safety parameters will be compared between both arms of the study. Furthermore, measures for quality of life, neurocognitive function as well as neuroimaging features will be evaluated prospectively.
- Conditions
- Glioblastoma
- Being tested
- SRT to the resection cavity
- Keywords
- glioblastoma, GBM, radiotherapy, Re-irradiation, progression
- Medical subject headings
- Glioblastoma, Disease Progression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SRT to the resection cavityRadiation
46 Gy total dose will be delivered in 2 Gy per fraction, or 36 Gy delivered in 3 Gy per fraction, 5 fractions within 1 week. Doses will have to cover 95% of the PTV with the prescribed dose. The clinical target volume (CTV) will be defined as the resection cavity of the recurrent glioblastoma plus a margin of 5mm. A CTV to PTV margin of 1 to 3mm will be added according to technique used for immobilisation.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: SRT to the resection cavity | Experimental | Postoperative stereotactic fractionated radiotherapy (SRT) to the resection cavity to a Total Dose of 46 Gy, 2 Gy single dose, or 36 Gy in 3 Gy single dose 5 fractions/week, depending on the volume and location of the treatment region. Receives: Radiation: SRT to the resection cavity |
| Arm B: Observation | No intervention | Observation without adjuvant radiotherapy. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS) at 12 months
PFS will be defined according to the MacDonald and RANO-Criteria; Complete remission: Remission of all contrast-enhanced lesions on CT or MRI without worsening of neurologic status
Partial remission: at least 50% remission of the contrast-enhancing lesions on CT or MRI without increase in steroid medication and without worsening of the neurologic status
Stable disease: Remission of the solid tumor/contrast-enhancing lesion on CT or MRI of less than 50% or progression of the solid tumor/contrast-enhancing lesion on CT or MRI of less than 25%, without increase in steroid medication of worsening of the neurologic status
Progression: Increase in solid tumor/contrast-enhancing lesion of 25% or more or development of a new lesion
Measured: 1 year
Secondary outcomes (4)
Overall survival
Patients will be followed up until death or for at least 1 year. Living patients will be censored according to the date of their last visit.
Measured: 1 year
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Safety and tolerability will be assessed by quality and quantity according to the International Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 for toxicity and adverse event reporting. Safety and toxicity of the study treatment will be evaluated by clinical neurological examination as well as neuro-imaging studies (MRI or CT).
Measured: 1 year
Quality of Life questionnaire
The EORTC QLQ-C30 version 3.0 questionnaire will be used to monitor for Quality of Life continuously throughout the treatment course as well as during follow up.
Measured: 1 year
Neurocognitive function
Neurocognitive function will be assessed at randomisation, at 6 months and at 12 months after randomization. A battery containing of 3 tests will be used. For assessment of learning, early and intermediate recall, the German version of the California Verbal Learning Test (CVLT) as well as the Regensburger Wortflüssigkeits-Test (RWT) will be used. Cognitive flexibility, speed as well as attention will be tested by the Trail-Making-Test. The tests at 6 and at 12 months will be compared to the result of the baseline measure as well as to each other.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2016 (estimated)
- Study startFeb 2016
- Primary completionFeb 2023 (estimated)
- Study completionFeb 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Technical University of MunichThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 162 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Technical University of Munich
- Sponsor type
- University, hospital or other
- Collaborators
- Helmholtz Zentrum München
- Responsible party
- Sponsor
- Investigators
- Stephanie E. Combs, Prof. Dr., Principal investigator, Klinik für RadioOnkologie und Strahlentherapie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02715297
- Sponsor's protocol ID
- RadOnc MRI TUM - 1
- Acronym
- GlioCave/NOA17
- Status last verified
- Mar 2020
- First submitted
- 29 Feb 2016
- Last updated
- 10 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Straube C, Scherb H, Gempt J, Kirschke J, Zimmer C, Schmidt-Graf F, Meyer B, Combs SE. Adjuvant stereotactic fractionated radiotherapy to the resection cavity in recurrent glioblastoma - the GlioCave study (NOA 17 - ARO 2016/3 - DKTK ROG trial). BMC Cancer. 2018 Jan 3;18(1):15. doi: 10.1186/s12885-017-3928-7.
PubMed 29298660
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjuvant Stereotactic Fractionated Radiotherapy to the Resection Cavity in Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT02715297
- Acronym / sponsor ID
- GlioCave/NOA17 / RadOnc MRI TUM - 1
- Conditions
- Glioblastoma
- Keywords
- glioblastoma, GBM, radiotherapy, Re-irradiation, progression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 162 participants (estimated)
- Lead sponsor
- Technical University of MunichUniversity, hospital or other
- Collaborators
- Helmholtz Zentrum München
- Study start
- Feb 2016
- Primary completion
- Feb 2023 (estimated)
- Study completion
- Feb 2023 (estimated)
- First posted
- 22 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.
This multi-center randomized controlled phase II trial will investigate the impact of stereotactic fractionated radiotherapy to the resection cavity of complete resected recurrent glioblastoma on progression free survival. As secondary endpoints, overall survival, safety and toxicity as well as early response criteria on MRI, quality of life and neurocognitive function will be assessed. Chemotherapy will not be part of the protocol, however, additional treatment will be possible upon investigators best choice.
Detailed description
The treatment of recurrent glioblastoma is, beside of its abundance in clinical practice, still under discussion. Patients presenting with recurrent disease are therefore treated within individual concepts, largely based on small prospective trials, retrospective evaluations or case reports. Therefore, the treatment ranges from best supportive care over primary systemic treatments towards local therapies such as radiotherapy or surgical resection. Even if there might be a large selection bias, local therapies with or without concomitant or adjuvant chemotherapy seem to promise the largest prognostic benefit. Whether the combination of surgical resection and adjuvant radiotherapy improves survival, as it does within the primary situation, is unknown.
The result of surgical resection might have an impact as well. Several case reports, retrospective evaluations and prospective studies have also included patients with remaining gross tumor after maximum save resection. In these trials, radiotherapy was associated with improvements in progression free as well as overall survival. Therefore, the influence of neuroimaging on prognosis is currently evaluated within the GLIA-A trial. Furthermore, stereotactic radiotherapy with or without an experimental systemic therapy is currently investigated within another multicenter randomized trial (NOA-12).
Whether patients might benefit from a postoperative radiotherapy of the resection cavity after complete extirpation of all macroscopic tumor is key question of this protocol.
To answer this question, the considered standard of care after complete resection, namely observation with or without adjuvant systemic therapy, will be compared to a postoperative normofractionated stereotactic radiotherapy towards the resection cavity within an open label, randomized trial. The prescribed total dose will be 46 Gy in 2 Gy fractions of 36 Gy in 3 Gy fractions depending on the treatment volume.
Concerning safety, side effects will be monitored prospectively. Safety parameters will be compared between both arms of the study. Furthermore, measures for quality of life, neurocognitive function as well as neuroimaging features will be evaluated prospectively.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: SRT to the resection cavity | Experimental | Radiation: SRT to the resection cavityPostoperative stereotactic fractionated radiotherapy (SRT) to the resection cavity to a Total Dose of 46 Gy, 2 Gy single dose, or 36 Gy in 3 Gy single dose 5 fractions/week, depending on the volume and location of the treatment region. |
| Arm B: Observation | No intervention | –Observation without adjuvant radiotherapy. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Unifocal, supratentorial recurrent glioblastoma
- Prior course of standard treatment
- Complete resection of all contrast enhancing areas
- age ≥ 18 years of age
- Karnofsky Performance Score 60% or higher
Key exclusion criteria (8 listed)
- Multifocal glioblastoma of gliomatosis cerebri
- Time interval of less than 6 months after primary radiotherapy
- Previous re-irradiation or prior radiosurgery of prior treatment with interstitial radioactive seeds
- refusal of the patients to take part in the study
- Patients who have not yet recovered from acute toxicities of prior therapies
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 |
|---|---|---|
| SRT to the resection cavity46 Gy total dose will be delivered in 2 Gy per fraction, or 36 Gy delivered in 3 Gy per fraction, 5 fractions within 1 week. Doses will have to cover 95% of the PTV with the prescribed dose. The clinical target volume (CTV) will be defined as the resection cavity of the recurrent glioblastoma plus a margin of 5mm. A CTV to PTV margin of 1 to 3mm will be added according to technique used for immobilisation. | Radiation | Arm A: SRT to the resection cavity |
Primary outcome
Progression free survival (PFS) at 12 months
Time frame: 1 year
PFS will be defined according to the MacDonald and RANO-Criteria; Complete remission: Remission of all contrast-enhanced lesions on CT or MRI without worsening of neurologic status Partial remission: at least 50% remission of the contrast-enhancing lesions on CT or MRI without increase in steroid medication and without worsening of the neurologic status Stable disease: Remission of the solid tumor/contrast-enhancing lesion on CT or MRI of less than 50% or progression of the solid tumor/contrast-enhancing lesion on CT or MRI of less than 25%, without increase in steroid medication of worsening of the neurologic status Progression: Increase in solid tumor/contrast-enhancing lesion of 25% or more or development of a new lesion
4 secondary outcomes
Overall survival
Time frame: 1 year
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Time frame: 1 year
Quality of Life questionnaire
Time frame: 1 year
Neurocognitive function
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2020.
- Derived from this study: PubMed 29298660Straube C, Scherb H, Gempt J, Kirschke J, Zimmer C, Schmidt-Graf F, Meyer B, Combs SE. Adjuvant stereotactic fractionated radiotherapy to the resection cavity in recurrent glioblastoma - the GlioCave study (NOA 17 - ARO 2016/3 - DKTK ROG trial). BMC Cancer. 2018 Jan 3;18(1):15. doi: 10.1186/s12885-017-3928-7.
- 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.
Stephanie E. Combs, Prof. Dr. principal investigator
Klinik für RadioOnkologie und Strahlentherapie
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SRT to the resection cavity in people with Glioblastoma, run by Technical University of Munich at 1 site in Germany.
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 8 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: status not confirmed, as of the sponsor's last update on 10 Mar 2020. 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 Germany. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Stephanie E. Combs, Prof. Dr. (0049 89-41404501, direktion.radonk@mri.tum.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (PFS) at 12 months (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02715297, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2020.