Trial Title:
Whole-Brain Radiotherapy (WBRT) Versus WBRT and Integrated Boost Using Helical Tomotherapy for Multiple Brain Metastases
NCT ID:
NCT00876759
Condition:
Brain Metastases
Conditions: Official terms:
Neoplasm Metastasis
Brain Neoplasms
Conditions: Keywords:
cerebral metastases
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Unknown status
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
whole brain radiotherapy
Description:
WBRT in 10 fractions to a total dose of 30Gy
Arm group label:
WBRT
Intervention type:
Radiation
Intervention name:
whole brain radiotherapy with simultaneous boost
Description:
Total dose: 10 fractions: whole brain total dose: 30Gy, metastases: total dose 50Gy
Arm group label:
WBRT with simulatneous boost
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 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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
- 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University Duisburg-Essen, Medical Faculty, department of Radiation Oncology
Address:
City:
Essen
Zip:
45122
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Andrea Wittig, MD
Phone:
+49201723
Phone ext:
2050
Email:
andrea.wittig@uni-due.de
Contact backup:
Last name:
Martin stuschke, MDpHD
Phone:
+49201723
Phone ext:
2321
Email:
martin.stuschke@uni-due.de
Investigator:
Last name:
Martin Stuschke, MD pHD
Email:
Principal Investigator
Facility:
Name:
Klinik für Strahlentherapie Charite Campus Mitte
Address:
City:
Berlin
Zip:
10117
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Volker Budach, MD pHD
Phone:
+49-30-450527
Phone ext:
021
Email:
volker.budach@charite.de
Contact backup:
Last name:
Simone Marnitz, MD pHD
Phone:
49-30-450527
Phone ext:
162
Email:
Simone.Marnitz@charite.de
Investigator:
Last name:
Volker Budach, MD pHD
Email:
Principal Investigator
Facility:
Name:
Universitätsklinikum Hamburg Eppendorf, Ambulanzzentrum des UKE GmbH, Bereich Strahlentherapie,
Address:
City:
Hamburg
Zip:
20246
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Rudolf Schwarz, MD pHD
Phone:
040 42803
Phone ext:
5425
Email:
rschwarz@uke.uni-hamburg.de
Investigator:
Last name:
Rudolf Schwarz, MDpHD
Email:
Principal Investigator
Facility:
Name:
Jürgen Debus
Address:
City:
Heidelberg
Zip:
69120
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Jürgen Debus, MD pHD
Phone:
+49-6221
Phone ext:
56 8202
Email:
juergen.debus@med.uni-heidelberg.de
Contact backup:
Last name:
Klaus Herfarth, MDpHD
Phone:
+49-6221
Phone ext:
56 8202
Email:
klaus.herfarth@med.uni-heidelberg.de
Investigator:
Last name:
Klaus Herfarth, MD pHD
Email:
Principal Investigator
Facility:
Name:
Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie, Klinikum rechts der Isar, Technische Universität München
Address:
City:
München
Zip:
81675
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Michael Molls, MD pHD
Phone:
+ 49 89 4140
Phone ext:
4501
Email:
Molls@lrz.tu-muenchen.de
Contact backup:
Last name:
Hans Geinitz, MD pHD
Phone:
089/4140
Phone ext:
4525
Email:
hans.geinitz@lrz.tu-muenchen.de
Investigator:
Last name:
Hans Geinitz, Md pHD
Email:
Principal Investigator
Start date:
April 2009
Completion date:
July 2013
Lead sponsor:
Agency:
University Hospital, Essen
Agency class:
Other
Source:
University Hospital, Essen
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT00876759
