Clinical trial NCT05378633: The CyberChallenge Trial How Much is Too Much - What is the Role of Cyberknife Radiosurgery in Patients With Multiple Brain Metastases?
Official title: The CyberChallenge Trial How Much is Too Much - What is the Role of Cyberknife Radiosurgery in Patients With Multiple Brain Metastases?
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Brain Metastases
Nsclc
Keywords: Metastases
Cyberknife
Lung Cancer
Lead sponsor: University Hospital Heidelberg
Sponsor class: OTHER
First posted: 2022-05-18
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: overall survival
timeFrame: time from randomisation until the date of death from any cause, assesd up to 24 month
measure: quality of life according to QLQ-C15 (questionaire for patients with advanced cancer referred for palliative radiotherapy
timeFrame: time from randomisation until the date of death from any cause, assesd up to 24 month
measure: quality of life according to BN-20 (questionaire for patients with brain neoplasm)
timeFrame: time from randomisation until the date of death from any cause, assesd up to 24 month
Secondary outcomes:
measure: functional independence assessed by the Barthel ADL index
timeFrame: time from randomisation until the date of death from any cause, assesd up to 24 month
measure: long-term cognitive Status (Hopkins Verbal Learning Test HVLT)
timeFrame: time from randomisation until the date of death from any cause, assesd up to 24 month
measure: development of radiation-induced brain lesions
timeFrame: time from randomisation until the date of death from any cause, assesd up to 24 month
measure: Radiation induced sideeffects
timeFrame: time from randomisation until the date of death from any cause, assesd up to 24 month
measure: Overall survival
timeFrame: time from randomisation until the date of death from any cause, assesd up to 24 month
measure: local progression of treated metastases
timeFrame: time from randomisation until the date of death from any cause, assesd up to 24 month
measure: intracranial progression of leptomeningeal disease
timeFrame: time from randomisation until the date of death from any cause, assesd up to 24 month
measure: intracranial progression of treated BM disease
timeFrame: time from randomisation until the date of death from any cause, assesd up to 24 month
measure: intracranial progression of new BM disease
timeFrame: time from randomisation until the date of death from any cause, assesd up to 24 month
measure: Brain salvage during follow-up
timeFrame: time from randomisation until the date of death from any cause, assesd up to 24 month
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: University Hospital of Heidelberg, Radiation Oncology
Study officials:
affiliation: Head of Department
name: Juergen Debus, Prof.
role: PRINCIPAL_INVESTIGATOR
References: