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

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.

Study Overview

• Status: Recruiting
• Conditions: Brain Metastases; Nsclc
• Intervention / Treatment: Radiation: SRS; Radiation: Whole Brain Radiotherapy

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.

• Study Type: Interventional
• Enrollment (Estimated): 190
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tanja Eichkorn, MD; Phone Number: 8201 06221 56; Email: tanja.eichkorn@med.uni-heidelbeg.de
• Study Contact Backup: Name: Adriane Hommertgen, PhD; Phone Number: 34091 06221 56; Email: adriane.hommertgen@med.uni-heidelberg.de

Study Locations

• Germany
  • Heidelberg, Germany, 69120
    • Recruiting
    • University Hospital of Heidelberg, Radiation Oncology
    • Contact: Jürgen Debus, Prof. Dr.; Phone Number: 8202 +49-6221-56; Email: juergen.debus@med.uni-heidelberg.de
    • Contact: Adriane Hommertgen; Phone Number: 34091 +49-6221-56; Email: adriane.hommertgen@med.uni-heidelberg.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Treatment Arm; Best Supportive Care + Stereotactic Radiotherapy of all Brain Metastases	Radiation: SRS; Stereotactic Radiotherapy (SRS)
Other: Standard Treatment Arm; Best Supportive Care ± Whole Brain Radiotherapy	Radiation: Whole Brain Radiotherapy; Whole Brain Radiotherapy (WBRT)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital Heidelberg
• Investigators: Principal Investigator: Juergen Debus, Prof., Head of Department

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2022
• Primary Completion (Estimated): February 24, 2027
• Study Completion (Estimated): February 24, 2028

Study Registration Dates

• First Submitted: January 24, 2022
• First Submitted That Met QC Criteria: May 13, 2022
• First Posted (Actual): May 18, 2022

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Lung Cancer; Metastases; Cyberknife
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Nervous System Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Central Nervous System Neoplasms; Pathological Conditions, Signs and Symptoms; Lung Neoplasms; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms
• Other Study ID Numbers: The CyberChallenge Trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No