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

Sponsor

University Hospital Heidelberg (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05871307

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Brain Metastases Radiotherapy	Radiation: Preoperative Radiotherapy Radiation: Intraoperative Radiation Radiation: Postoperative Radiotherapy	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

May 1, 2026

Anticipated Study Completion Date :

May 1, 2028

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Radiotherapy, University of Heidelberg	Heidelberg		Germany	69120

Sponsors and Collaborators

University Hospital Heidelberg

Investigators

Principal Investigator: Jürgen Debus, Prof., University Hospital of Heidelberg, Radiation Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Juergen Debus, Department Director, University Hospital Heidelberg

ClinicalTrials.gov Identifier:

NCT05871307

Other Study ID Numbers:

RADOnk-Radcav

First Posted:

May 23, 2023

Last Update Posted:

May 23, 2023

Last Verified:

Nov 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Juergen Debus, Department Director, University Hospital Heidelberg

Brain Metastases

Radiotherapy

Additional relevant MeSH terms:

Neoplasm Metastasis

Brain Neoplasms

Study Results

No Results Posted as of May 23, 2023