Brain MetastasesPhase 2NCT00876759
Whole-Brain Radiotherapy (WBRT) Versus WBRT and Integrated Boost Using Helical Tomotherapy for Multiple Brain Metastases
A Phase 2 study testing whole brain radiotherapy and whole brain radiotherapy with simultaneous boost in people with Brain Metastases, run by University Hospital, Essen at 5 sites in Germany.
Trial summary
Brain metastases occur in 20-40% of patients with primary extracerebral tumors. Despite important advances in therapy of malignant solid tumors and treatment of 1-3 brain metastases, multiple brain metastases continue to present a significant problem in attempting to prevent progression of disease and limit morbidity… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Metastases
- What is being tested?
- whole brain radiotherapy and whole brain radiotherapy with simultaneous boost
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 5 sitesGermany
- Study dates
- Apr 2009to Jul 2013
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed extracranial primary malignancy other than small cell lung cancer, germ cell tumor and lymphoma. Histological confirmation may have been from the primary tumor site, from another metastatic site, or from the metastatic brain lesion(s)
- 4-10 brain metastases, which are radiologically proven by MRI scan. The size of each metastasis must be between 3 mm and 4.0 cm in the largest diameter. Contrast-enhancements on MRI which are smaller than 3 mm in diameter are not considered. The total volume of the lesions must be smaller than 35 ml and the volume of perilesional normal brain receiving more than 4 Gy per fraction must be smaller than 40 ml. An evaluation of the latter criterion is strongly recommended for total lesions volume > 20 ml prior to randomization of the patient according to figure 1. OR
- 2-3 brain metastases, which are radiologically proven by MRI scan. The size of each metastasis must be between 3 mm and 4.0 cm in the largest diameter. Contrast-enhancements on MRI which are smaller than 3 mm in diameter are not considered. The patient should not be considered as a good candidate for stereotactic radiosurgery +/- whole brain radiotherapy.
- Each lesion has a distance of its margin to the chiasma opticum or the optic nerves of > 5 mm.
- Male or female, Age 18 years or older
- Laboratory requirements: hematological status must be documented.
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- Platelets >30 x 109/l. If platelets are below 30 x 109/l then correction by transfusion is indicated before entry into the study according to institutional guidelines.
- Hemoglobin > 8 g/dl. If anemia is present to the extent that the hemoglobin is less than 8 g/dl then correction by transfusion and/or erythropoietin is indicated before entry into the study according to institutional guidelines.
- Before patient registration, written informed consent must be given according to ICH/GCP and national regulations.
Who cannot join
- Lesions located in the medulla oblongata or in the brainstem.
- Leptomeningeal metastases or meningosis carcinomatosa. If meningosis carcinomatosa is suspected on MRI, the presence of tumor cells in the liquor cerebrospinalis must be excluded prior study entry.
- Chemotherapy within 1 week prior to study treatment
- Need for systemic chemotherapy to control primary disease or extracranial metastases within 3 weeks after study treatment (assessed before randomization)
- Prior treatment for brain metastases other than chemotherapy or resection of brain metastases (with 2-10 measurable lesions remaining), prior cranial radiotherapy
- Severe coagulopathy
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- Medical illnesses or psychiatric impairments which would prevent completion of protocol therapy
- Female patients who are pregnant at the time of entering the study. Women must agree to a beta-HCG pregnancy test if the possibility of pregnancy is believed to exist. Women and men of child bearing potential who are admitted to the trial will be advised that the treatment received may be teratogenic and are advised to take adequate measures to prevent conception.
- Participation in other clinical trials within 4 weeks prior registration.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Germany5 sites, 5 recruiting
- Not yet recruiting
Klinik für Strahlentherapie Charite Campus Mitte
Berlin, 10117
Volker Budach, MD pHD, +49-30-450527 ext. 021, volker.budach@charite.de
Simone Marnitz, MD pHD, 49-30-450527 ext. 162, Simone.Marnitz@charite.de
- Recruiting
University Duisburg-Essen, Medical Faculty, department of Radiation Oncology
Essen, North Rhine-Westphalia, 45122
Andrea Wittig, MD, +49201723 ext. 2050, andrea.wittig@uni-due.de
Martin stuschke, MDpHD, +49201723 ext. 2321, martin.stuschke@uni-due.de
- Not yet recruiting
Universitätsklinikum Hamburg Eppendorf, Ambulanzzentrum des UKE GmbH, Bereich Strahlentherapie,
Hamburg, 20246
Rudolf Schwarz, MD pHD, 040 42803 ext. 5425, rschwarz@uke.uni-hamburg.de
Rudolf Schwarz, MDpHD
- Not yet recruiting
Jürgen Debus
Heidelberg, 69120
Jürgen Debus, MD pHD, +49-6221 ext. 56 8202, juergen.debus@med.uni-heidelberg.de
Klaus Herfarth, MDpHD, +49-6221 ext. 56 8202, klaus.herfarth@med.uni-heidelberg.de
- Not yet recruiting
Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie, Klinikum rechts der Isar, Technische Universität München
München, 81675
Michael Molls, MD pHD, + 49 89 4140 ext. 4501, Molls@lrz.tu-muenchen.de
Hans Geinitz, MD pHD, 089/4140 ext. 4525, hans.geinitz@lrz.tu-muenchen.de
About this study
Official title: Whole-Brain Radiotherapy (WBRT) vs. WBRT and Integrated Boost Using Helical Tomotherapy for Patients With Multiple Brain Metastases - a Multicentre Randomized Phase II Trial
Brain metastases occur in 20-40% of patients with primary extracerebral tumors. Despite important advances in therapy of malignant solid tumors and treatment of 1-3 brain metastases, multiple brain metastases continue to present a significant problem in attempting to prevent progression of disease and limit morbidity associated with therapy. The majority of patients who develop brain metastases have a short survival, effective palliation being transient. The median survival after diagnosis is as low as 3-6 months. However, there is some evidence that selected patients survive prolonged periods with vigorous therapeutic approach.
Specific therapeutic options are surgery, chemotherapy, conventional fractionated whole-brain radiotherapy (WBRT) and radiosurgery. Radiosurgery allows delivering of a single high dose fraction of radiation to targets of 3-3.5 cm maximum diameter. In patients with newly diagnosed brain metastases, a rapid decrease of symptoms, local tumor response rate of 73-90% and a median survival of 7-12 month have been reported.
Read more
WBRT alone is the treatment of choice for patients with multiple brain metastases, and for patients with single brain metastases not amenable to surgery or radiosurgery. Median survival after WBRT alone is 3-6 months.
WBRT and radiosurgery boost have been shown to improve survival in RPA class I patients and in patients with favorable histological status and squamous cell or non-small cell lung tumors. All randomized trials showed improved local control with the addition of radiosurgery to WBRT (Andrews, 2004).
WBRT in conjunction with radiosurgery improves local control and reduces the risk of new distant brain metastases, but most studies support that combined radiosurgery and WBRT does not improve the overall survival expect for patients without evidence of extracranial disease.
Helical Tomotherapy (HT) allows as a sole modality a new treatment option: Using HT, the advantage of applying a highly conformal boost dose to the metastases and WBRT can be combined in one treatment session. Therefore, it allows applying a high dose to multiple brain metastases in the sense of an integrated boost. The focus of this study is to investigate the efficacy and safety of WBRT with an integrated boost using this new treatment modality in comparison to the effects of conventional WBRT alone.
The principal objective of the trial is to assess the therapeutic efficacy of WBRT as compared to WBRT combined with integrated boost with HT delivered to patients with 2-10 brain metastases of solid tumors. The secondary objective is to evaluate the safety of WBRT as opposed to WBRT combined with integrated boost as delivered by HT in patients with 2-10 brain metastases.
- Conditions
- Brain Metastases
- Being tested
- whole brain radiotherapy, whole brain radiotherapy with simultaneous boost
- Keywords
- cerebral metastases
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
whole brain radiotherapyRadiation
WBRT in 10 fractions to a total dose of 30Gy
whole brain radiotherapy with simultaneous boostRadiation
Total dose: 10 fractions: whole brain total dose: 30Gy, metastases: total dose 50Gy
| Study group | Role | What they receive |
|---|---|---|
| WBRT | Active comparator | standard WBRT to a total dose of 30 Gy in 10 fractions Receives: Radiation: whole brain radiotherapy |
| WBRT with simulatneous boost | Experimental | The experimental group will be treated with helical tomotherapy giving 3 Gy per fraction to the whole brain up to a total dose of 30 Gy in 10 fractions and raising the prescribed dose to the brain metastases to 5 Gy per fraction. The dose fall off to the normal brain should be as steep as possible around each brain metastasis. The optic chiasm and the optic nerves should not receive more than 3.5 Gy per fraction. Receives: Radiation: whole brain radiotherapy with simultaneous boost |
What is being measured
The primary outcome is the main question the study is designed to answer.
time to morphologic progression in the brain as evidenced on MRI (RECIST criteria)
Measured: 2 years
Secondary outcomes (6)
local tumor control as evidenced by MRI
Measured: 2 years
time to neurocognitive progression
Measured: 2 years
time to deterioration of functional independence
Measured: 2 years
quality of life
Measured: 2 years
overall survival, cause of death distribution
Measured: 2 years
toxicity as evidenced by CTC-criteria
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2009 (estimated)
- Study startApr 2009
- Primary completionJul 2011 (estimated)
- Study completionJul 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain MetastasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Essen
- Sponsor type
- University, hospital or other
- Investigators
- Martin Stuschke, MD pHD, Principal investigator, University Duisburg-Essen, Medical Faculty, Department of Radiation Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00876759
- Sponsor's protocol ID
- Tomo0701
- Status last verified
- Apr 2009
- First submitted
- 6 Apr 2009
- Last updated
- 7 Apr 2009
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Whole-Brain Radiotherapy (WBRT) vs. WBRT and Integrated Boost Using Helical Tomotherapy for Patients With Multiple Brain Metastases - a Multicentre Randomized Phase II Trial
- ClinicalTrials.gov ID
- NCT00876759
- Acronym / sponsor ID
- Tomo0701
- Conditions
- Brain Metastases
- Keywords
- cerebral metastases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- University Hospital, EssenUniversity, hospital or other
- Study start
- Apr 2009
- Primary completion
- Jul 2011 (estimated)
- Study completion
- Jul 2013 (estimated)
- First posted
- 7 Apr 2009 (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.
Brain metastases occur in 20-40% of patients with primary extracerebral tumors. Despite important advances in therapy of malignant solid tumors and treatment of 1-3 brain metastases, multiple brain metastases continue to present a significant problem in attempting to prevent progression of disease and limit morbidity associated with therapy. The majority of patients who develop brain metastases have a short survival, effective palliation being transient. The median survival after diagnosis is as low as 3-6 months. However, there is some evidence that selected patients survive prolonged periods with vigorous therapeutic approach.
Specific therapeutic options are surgery, chemotherapy, conventional fractionated whole-brain radiotherapy (WBRT) and radiosurgery. Radiosurgery allows delivering of a single high dose fraction of radiation to targets of 3-3.5 cm maximum diameter. In patients with newly diagnosed brain metastases, a rapid decrease of symptoms, local tumor response rate of 73-90% and a median survival of 7-12 month have been reported.
WBRT alone is the treatment of choice for patients with multiple brain metastases, and for patients with single brain metastases not amenable to surgery or radiosurgery. Median survival after WBRT alone is 3-6 months.
WBRT and radiosurgery boost have been shown to improve survival in RPA class I patients and in patients with favorable histological status and squamous cell or non-small cell lung tumors. All randomized trials showed improved local control with the addition of radiosurgery to WBRT (Andrews, 2004).
WBRT in conjunction with radiosurgery improves local control and reduces the risk of new distant brain metastases, but most studies support that combined radiosurgery and WBRT does not improve the overall survival expect for patients without evidence of extracranial disease.
Helical Tomotherapy (HT) allows as a sole modality a new treatment option: Using HT, the advantage of applying a highly conformal boost dose to the metastases and WBRT can be combined in one treatment session. Therefore, it allows applying a high dose to multiple brain metastases in the sense of an integrated boost. The focus of this study is to investigate the efficacy and safety of WBRT with an integrated boost using this new treatment modality in comparison to the effects of conventional WBRT alone.
The principal objective of the trial is to assess the therapeutic efficacy of WBRT as compared to WBRT combined with integrated boost with HT delivered to patients with 2-10 brain metastases of solid tumors. The secondary objective is to evaluate the safety of WBRT as opposed to WBRT combined with integrated boost as delivered by HT in patients with 2-10 brain metastases.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| WBRT | Active comparator | Radiation: whole brain radiotherapystandard WBRT to a total dose of 30 Gy in 10 fractions |
| WBRT with simulatneous boost | Experimental | Radiation: whole brain radiotherapy with simultaneous boostThe experimental group will be treated with helical tomotherapy giving 3 Gy per fraction to the whole brain up to a total dose of 30 Gy in 10 fractions and raising the prescribed dose to the brain metastases to 5 Gy per fraction. The dose fall off to the normal brain should be as steep as possible around each brain metastasis. The optic chiasm and the optic nerves should not receive more than 3.5 Gy per fraction. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histologically or cytologically confirmed extracranial primary malignancy other than small cell lung cancer, germ cell tumor and lymphoma. Histological confirmation may have been from the primary tumor site, from another metastatic site, or from the metastatic brain lesion(s)
- 4-10 brain metastases, which are radiologically proven by MRI scan. The size of each metastasis must be between 3 mm and 4.0 cm in the largest diameter. Contrast-enhancements on MRI which are smaller than 3 mm in diameter are not considered. The total volume of the lesions must be smaller than 35 ml and the volume of perilesional normal brain receiving more than 4 Gy per fraction must be smaller than 40 ml. An evaluation of the latter criterion is strongly recommended for total lesions volume > 20 ml prior to randomization of the patient according to figure 1. OR
- 2-3 brain metastases, which are radiologically proven by MRI scan. The size of each metastasis must be between 3 mm and 4.0 cm in the largest diameter. Contrast-enhancements on MRI which are smaller than 3 mm in diameter are not considered. The patient should not be considered as a good candidate for stereotactic radiosurgery +/- whole brain radiotherapy.
- Each lesion has a distance of its margin to the chiasma opticum or the optic nerves of > 5 mm.
- Male or female, Age 18 years or older
Key exclusion criteria (9 listed)
- Lesions located in the medulla oblongata or in the brainstem.
- Leptomeningeal metastases or meningosis carcinomatosa. If meningosis carcinomatosa is suspected on MRI, the presence of tumor cells in the liquor cerebrospinalis must be excluded prior study entry.
- Chemotherapy within 1 week prior to study treatment
- Need for systemic chemotherapy to control primary disease or extracranial metastases within 3 weeks after study treatment (assessed before randomization)
- Prior treatment for brain metastases other than chemotherapy or resection of brain metastases (with 2-10 measurable lesions remaining), prior cranial radiotherapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| whole brain radiotherapyWBRT in 10 fractions to a total dose of 30Gy | Radiation | WBRT |
| whole brain radiotherapy with simultaneous boostTotal dose: 10 fractions: whole brain total dose: 30Gy, metastases: total dose 50Gy | Radiation | WBRT with simulatneous boost |
Primary outcome
time to morphologic progression in the brain as evidenced on MRI (RECIST criteria)
Time frame: 2 years
6 secondary outcomes
local tumor control as evidenced by MRI
Time frame: 2 years
time to neurocognitive progression
Time frame: 2 years
time to deterioration of functional independence
Time frame: 2 years
quality of life
Time frame: 2 years
overall survival, cause of death distribution
Time frame: 2 years
toxicity as evidenced by CTC-criteria
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2009.
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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.
Martin Stuschke, MD pHD principal investigator
University Duisburg-Essen, Medical Faculty, Department of Radiation Oncology
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing whole brain radiotherapy and whole brain radiotherapy with simultaneous boost in people with Brain Metastases, run by University Hospital, Essen at 5 sites 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 9 inclusion and 9 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 7 Apr 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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 Andrea Wittig, MD (+49201723 ext. 2050, andrea.wittig@uni-due.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
time to morphologic progression in the brain as evidenced on MRI (RECIST criteria) (time frame: 2 years). 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 7 Apr 2009.