Cerebral Metastases of Solid Cancers
Conditions
Brief summary
Phase III trial comparing local control and side effects after fractionated stereotactic radiotherapy and single session radiosurgery in patients with larger brain metastases (2-4 cm)
Detailed description
This is a prospective, multicenter randomized trial comparing local control and side effects after fractionated stereotactic radiotherapy with 12 x 4 Gy and single session radiosurgery according to RTOG 9005 in patients with larger brain metastases (2-4 cm). Patients will be randomized to either fractionated stereotactic radiotherapy with 12 x 4 Gy or radiosurgery with 1 x 18 Gy (2-3 cm) or 1 x 15 Gy (3-4 cm) as defined by the RTOG 9005. Randomization will be stratified by metastasis volume and histology.
Interventions
RADIATIONRadiosurgery
Radiosurgery with 1 x 18 Gy (2-3 cm) or 1 x 15 Gy (3-4 cm)
Fractionated stereotactic radiotherapy with 12 x 4 Gy and 2 mm
Sponsors
University of Erlangen-Nürnberg Medical School
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, multicenter, Open-Label, randomized
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years, no upper age limit * Karnofsky Performance Score \> 50 points * Expected Survival \> 3 months * 1-10 cerebral metastases of metastatic solid cancer * Indication for local radiotherapy * Patients must be able to understand the protocol and provide informed consent
Exclusion criteria
* Whole Brain radiotherapy no longer than 6 weeks before the start of stereotactic radiotherapy or planned whole brain radiotherapy after stereotactic radiotherapy * Prior irradiation of the cerebral metastasis that is to be treated in the study * Relevant overlap of prior radiation fields with the metastasis that is to be treated in the study * Metastasis in the brainstem * Contraindication for cerebral MRI * Metastasis that is to be treated in the study can't be visualized in contrast-enhanced T1 MRI sequence * Pregnant or lactating women * Abuse of illicit drugs, alcohol or medication * Patient not able or willing to behave according to protocol * Participation in another clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to local progression - TTLP | 12 months | Local progression will be defined according to the RANO-BM criteria by an increase of at least 20% in the longest diameter of the metastasis relative to nadir or baseline. In addition to the relative increase of 20% the lesion must increase by an absolute value of 5 mm or more. TTLP is defined as the time from randomization until the detection of progression as per the RANO-BM criteria. Patients will be censored if they have no signs of local progression at the time of last tumor monitoring during follow-up or at the onset of one of the following competing risk events not associated with local progression: death, lost to follow up, unauthorized non-protocol treatment of the target lesion. Confirmatory analysis of the primary endpoint variable will be performed using a p-value of p≤0.05 as the global significance level. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to local progression (Volumetric RANO-BM criteria) | 12 months | Based on the RANO-BM criteria, progression is defined as an increase in volume of 72.8% or more (corresponds to a 20% increase in diameter for a perfect sphere). |
| Quality of Life according to EORTC QLQ-C30 | Change from baseline to 3, 6, 12 and 24 months | Quality of life measured by European Organization for Research and Treatment of Cancer (EORTC) questionnaire QLQ C30 |
| CNS toxicity according to CTCAE v5.0 | 12 months | CNS toxicity according to CTCAE v5.0 |
| Overall Survival | 24 months | Overall Survival |
| Quality of Life according to EORTC QLQ-BN20 | Change from baseline to 3, 6, 12 and 24 months | Quality of life measured by European Organization for Research and Treatment of Cancer (EORTC) questionnaire QLQ BN20 |
| Local-Progression-Free Survival | 12 months | Local-Progression-Free Survival is defined like TTLP except that death not associated with local progression will not be censored but assessed as a separate event |
Countries
Germany
Contacts
Primary ContactFlorian Putz, PD Dr. med.
Outcome results
None listed