Neoadjuvant vs. Intraoperative vs. Adjuvant Resection Cavity Radiotherapy of Brain Metastases

Study Purpose

Patients suffering from malignancies in advanced stages often develop brain metastases, which limit both the life span and the quality of life. Combining surgery and radiotherapy for resectable brain metastases is standard of care but there is a lot of controversy on which kind of radiotherapy is best suitable. Recently, first volumetric in-silico analyses point to theoretical advantages of neoadjuvant stereotactic radiotherapy of brain metastases. Special about this trial is the direct comparison between the three currently discussed radiotherapy options for resectable brain metastases: Neoadjuvant stereotactic radiotherapy, intraoperative radiotherapy and adjuvant stereotactic radiotherapy.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- Histologically confirmed solid malignancy.

- Metastatic brain disease (1-10 brain metastases), with at least one brain metastasis in a non-eloquent location (i.e. motor or speech) planned for resection.

- Maximum size of the brain metastasis <5cm.

- Eligibility of patients for both stereotactic radiotherapy and resection.

- Time interval from resection to adjuvant stereotactic radiosurgery of 2-6 weeks.

- Time interval from neoadjuvant stereotactic radiosurgery to resection of 1-7 days.

- Possibility to postpone resection for neoadjuvant stereotactic radiosurgery, if applicable.

- Karnofsky performance scores >= 70 or Eastern Cooperative Oncology Group (ECOG) >= 2 at enrollment.

- 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:
Necessity of immediate surgical resection due to life threatening symptoms.

- brain metastasis directly located (≤10mm) next to the optic system or brain stem.

- Refusal of the patients to take part in the study.

- Small-cell lung cancer (SCLC) or hematologic malignancy as primary malignant illness.

- Leptomeningeal disease suspected RadCav Trial Protocol Version 1.1, 01.07.2022 18.

- Previous radiotherapy of the brain.

- Contraindication for contrast-enhanced MRI.

- Pregnant or lactating women.

- Participation in another competing clinical study or observation period of competing trials, respectively

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05871307
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	University Hospital Heidelberg
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Jürgen Debus, Prof.
Principal Investigator Affiliation	University Hospital of Heidelberg, Radiation Oncology
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries	Germany
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Brain Metastases, Radiotherapy

Additional Details

This trial approach allows for detailed comparison of resected tissue samples, cerebrospinal fluid and blood of all patient groups. So, the investigators will investigate biomaterial of recently irradiated (neoadjuvant and intraoperative arms) and non-irradiated (adjuvant arm) tissue. All this prompts the main issues of the explorative randomized controlled phase 2 RADCAV trial: Is there a difference between neoadjuvant stereotactic radiotherapy vs.#46; intraoperative radiotherapy vs.#46; adjuvant stereotactic radiotherapy regarding the factors immune profiling, dosimetry, efficacy and toxicity. It can be hypothesized that the resected tissue differs between recently irradiated and non-irradiated brain metastases, for example regarding different histopathologic and molecular pathologic markers including immune environment, markers for cell death and markers for tumor invasion. Are there histopathologic and molecular pathologic markers of tumor cell response and prognosis so the investigators can better understand the effects of irradiation on metastatic brain tissue? And are there relevant differences in dosimetry that put patients at different risks for efficacy and toxicity?

Arms & Interventions

Arms

Experimental: Experimental Arm A (Preoperativ SRS)

Preoperative stereotatic radiosurgery following resection of brain metastases after 1-7 days

Experimental: Experimental Arm B (Intraoperativ SRS)

Intraoperative stereotactic radiotherapy after resection of brain metastases

Active Comparator: Standard Treatment Arm C (Posoperativ SRS)

Resection of brain metastases following stereotactic radiotherapy after 2-6 weeks

Interventions

Radiation: - Preoperative Radiotherapy

Resection of brain mestases following

Radiation: - Intraoperative Radiation

While Resection

Radiation: - Postoperative Radiotherapy

After resection

Contact a Trial Team

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