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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?

Phase 2
Recruiting
Conditions
Nsclc
Brain Metastases
Interventions
Radiation: Whole Brain Radiotherapy
Radiation: SRS
Registration Number
NCT05378633
Lead Sponsor
University Hospital Heidelberg
Brief Summary

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

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
190
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Standard Treatment ArmWhole Brain RadiotherapyBest Supportive Care ± Whole Brain Radiotherapy
Experimental Treatment ArmSRSBest Supportive Care + Stereotactic Radiotherapy of all Brain Metastases
Primary Outcome Measures
NameTimeMethod
quality of life according to BN-20 (questionaire for patients with brain neoplasm)time from randomisation until the date of death from any cause, assesd up to 24 month

changes in BN-20 scores, scale is 1-100 points, 100 points representing maximum score

overall survivaltime from randomisation until the date of death from any cause, assesd up to 24 month

number of alive patients

quality of life according to QLQ-C15 (questionaire for patients with advanced cancer referred for palliative radiotherapytime from randomisation until the date of death from any cause, assesd up to 24 month

changes in QLQ-C15 scores, scale is 1-100 points, 100 points representing maximum score

Secondary Outcome Measures
NameTimeMethod
intracranial progression of treated BM diseasetime from randomisation until the date of death from any cause, assesd up to 24 month

recurrence of treated BM disease

long-term cognitive Status (Hopkins Verbal Learning Test HVLT)time from randomisation until the date of death from any cause, assesd up to 24 month

Changes in HVLT scores (minimum 0, maximum 12)

development of radiation-induced brain lesionstime from randomisation until the date of death from any cause, assesd up to 24 month

changes in amounts of Radiation-induced brain lesions

intracranial progression of leptomeningeal diseasetime from randomisation until the date of death from any cause, assesd up to 24 month

occurrence of leptomeningeal disease

functional independence assessed by the Barthel ADL indextime from randomisation until the date of death from any cause, assesd up to 24 month

Changes in Barthel ADL index scores, scale 0-100 points

Overall survivaltime from randomisation until the date of death from any cause, assesd up to 24 month

amount of alive randomized patients enrolled in the trial

Brain salvage during follow-uptime from randomisation until the date of death from any cause, assesd up to 24 month

medical idication for whole brain Radiation after inital stereotactic radiotherapy

Radiation induced sideeffectstime from randomisation until the date of death from any cause, assesd up to 24 month

changes in toxicity rates according to CTCAE 5.0

local progression of treated metastasestime from randomisation until the date of death from any cause, assesd up to 24 month

detectable progressive disease of treated metastases

intracranial progression of new BM diseasetime from randomisation until the date of death from any cause, assesd up to 24 month

occurrence of new BM disease

Trial Locations

Locations (1)

University Hospital of Heidelberg, Radiation Oncology

🇩🇪

Heidelberg, Germany

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