The CyberChallenge Trial How Much is Too Much - What is the Role of Cyberknife Radiosurgery in Patients With Multiple Brain Metastases?

Study Overview
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Brief Summary
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Patients suffering from malignancies in advanced stages often develop brain metastases, which limit both the life span and the quality of life. Therapy options for multiple brain metastases may vary and range from stereotactic radiosurgery (SRS), whole-brain radiotherapy (WBRT), chemotherapy, immunotherapy to palliative best supportive care. Especially the efficacy and toxicity of SRS compared to WBRT in patients with extensive brain metastases (>4) is not yet clear but of incremental relevance in this seriously ill cohort with a limited life span. These health-impaired patients might especially profit from a less toxic treatment that is also time sparing with 1 or few sessions in SRS versus 10 sessions in WBRT. On the other hand, no compromises in efficacy want to be done.

Detailed Description
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In the present multicenter study, the benefit of SRS compared to conventional whole brain radiotherapy, each combined with best supportive care or best supportive care only, in patients with 4-15 brain metastases is to be prospectively investigated. The effect will be measured using quality-adjusted life-years (QUALY). Quality of life and overall survival are therefore primary endpoints. Secondary endpoints are the ability to perform basic activities of daily life (Barthel (ADL) index), progression-free survival, local and locoregional progression-free survival, extracranial progression, toxicity and its treatment, the recording of postherapeutic radiation-induced brain lesions (RIBL), long-term cognitive function, a possible salvage therapy as well as death from brain metastases. Furthermore, die CyberChallenge trial is linked to a translational program via BUB2 study. The BUB2 study conducts biobanking of blood, urine and resection or biopsy material, if available, as well as collects imaging material. This is to find diagnostic and prognostic biomarkers in our cancer patients via analyzing genetic, epigenetic and protein expression patterns as well as radiomics and correlating them to clinical data and therefore further push individualized patient care in brain metastases forward.

Official Title
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The CyberChallenge Trial How Much is Too Much - What is the Role of Cyberknife Radiosurgery in Patients With Multiple Brain Metastases?

Conditions
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Brain Metastases, Nsclc

Intervention / Treatment
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* Radiation: SRS
* Radiation: Whole Brain Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically confirmed malignant illness 4-15 suspect intracranial lesions, taking into consideration all available MRI series age ≥ 18 years of age 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) Exclusion Criteria: Refusal of the patients to take part in the study Inability to tolerate irradiation consistent with the protocol Small-cell lung cancer (SCLC) or lymphoma as primary malignant illness >15 suspect intracranial lesions, taking into consideration all available MRI series leptomeningeal disease Previous radiotherapy of the brain Patients who have not yet recovered from acute high-grade toxicities of prior therapies Pregnant or lactating women Participation in another competing clinical study or observation period of competing trials, respectively MRI contraindication (i.e. cardiac pacemaker, implanted defibrillator, certain cardiac valve replacements, certain metal implants)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Treatment Arm<br>Best Supportive Care + Stereotactic Radiotherapy of all Brain Metastases | Radiation: SRS<br>* Stereotactic Radiotherapy (SRS)<br>|
| Other: Standard Treatment Arm<br>Best Supportive Care ± Whole Brain Radiotherapy | Radiation: Whole Brain Radiotherapy<br>* Whole Brain Radiotherapy (WBRT)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | number of alive patients | time from randomisation until the date of death from any cause, assesd up to 24 month | 
| quality of life according to QLQ-C15 (questionaire for patients with advanced cancer referred for palliative radiotherapy | changes in QLQ-C15 scores, scale is 1-100 points, 100 points representing maximum score | time from randomisation until the date of death from any cause, assesd up to 24 month | 
| quality of life according to BN-20 (questionaire for patients with brain neoplasm) | changes in BN-20 scores, scale is 1-100 points, 100 points representing maximum score | time from randomisation until the date of death from any cause, assesd up to 24 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| functional independence assessed by the Barthel ADL index | Changes in Barthel ADL index scores, scale 0-100 points | time from randomisation until the date of death from any cause, assesd up to 24 month | 
| long-term cognitive Status (Hopkins Verbal Learning Test HVLT) | Changes in HVLT scores (minimum 0, maximum 12) | time from randomisation until the date of death from any cause, assesd up to 24 month | 
| development of radiation-induced brain lesions | changes in amounts of Radiation-induced brain lesions | time from randomisation until the date of death from any cause, assesd up to 24 month | 
| Radiation induced sideeffects | changes in toxicity rates according to CTCAE 5.0 | time from randomisation until the date of death from any cause, assesd up to 24 month | 
| Overall survival | amount of alive randomized patients enrolled in the trial | time from randomisation until the date of death from any cause, assesd up to 24 month | 
| local progression of treated metastases | detectable progressive disease of treated metastases | time from randomisation until the date of death from any cause, assesd up to 24 month | 
| intracranial progression of leptomeningeal disease | occurrence of leptomeningeal disease | time from randomisation until the date of death from any cause, assesd up to 24 month | 
| intracranial progression of treated BM disease | recurrence of treated BM disease | time from randomisation until the date of death from any cause, assesd up to 24 month | 
| intracranial progression of new BM disease | occurrence of new BM disease | time from randomisation until the date of death from any cause, assesd up to 24 month | 
| Brain salvage during follow-up | medical idication for whole brain Radiation after inital stereotactic radiotherapy | time from randomisation until the date of death from any cause, assesd up to 24 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastases, Cyberknife, Lung Cancer