Neoadjuvant vs. Intraoperative vs. Adjuvant Resection Cavity Radiotherapy of Brain Metastases (Radcav)

Neoadjuvant vs. Intraoperative vs. Adjuvant Resection Cavity Radiotherapy of Brain Metastases - A Prospective Randomized Explorative Phase II Trial

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Brain Metastases; Radiotherapy
• Intervention / Treatment: Radiation: Preoperative Radiotherapy; Radiation: Intraoperative Radiation; Radiation: Postoperative Radiotherapy

Detailed Description

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. intraoperative radiotherapy vs. 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?

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Heidelberg, Germany, 69120
    • Department of Radiotherapy, University of Heidelberg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Arm A (Preoperativ SRS); Preoperative stereotatic radiosurgery following resection of brain metastases after 1-7 days	Radiation: Preoperative Radiotherapy; Resection of brain mestases following
Experimental: Experimental Arm B (Intraoperativ SRS); Intraoperative stereotactic radiotherapy after resection of brain metastases	Radiation: Intraoperative Radiation; While Resection
Active Comparator: Standard Treatment Arm C (Posoperativ SRS); Resection of brain metastases following stereotactic radiotherapy after 2-6 weeks	Radiation: Postoperative Radiotherapy; After resection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of treatment response	number of patients without progresion according to RANO-BM	through study completion, an avarage of 60 month
local tumor control	events of tumor progression or recurrence in the area of 1cm surrounding the resection cavity and surrounding the surgical access	through study completion, an avarage of 60 month

Collaborators and Investigators

• Sponsor: University Hospital Heidelberg
• Investigators: Principal Investigator: Laila König, Prof. Dr., University Hospital of Heidelberg, Radiation Oncology

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: November 2, 2022
• First Submitted That Met QC Criteria: May 12, 2023
• First Posted (Actual): May 23, 2023

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Radiotherapy; Brain Metastases
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Neoplasms
• Other Study ID Numbers: RADOnk-Radcav

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