Intraoperative Radiotherapy After the Resection of Brain Metastases (INTRAMET)

Intraoperative Radiotherapy After the Resection of Brain Metastases - a Phase II Feasibility Study

INTRAMET examines prospectively the effectiveness of an intraoperative radiotherapy immediate after the surgical resection of brain metastases. Patients won't receive further radiation therapy of the intraoperatively treated lesion.

Study Overview

• Status: Recruiting
• Conditions: Brain Metastases
• Intervention / Treatment: Radiation: Intraoperative Radiotherapy

Detailed Description

Brain metastases occur in up to 40% of all patients diagnosed with systemic cancer. Without adjuvant radiotherapy after resection of space occupying lesions local recurrence rates are high. That is why guidelines recommend a cavity boosting with x-rays. External beam radiotherapy can lower the risk of local recurrence but means longer hospitalization, prolongs the time to systemic salvage therapies and bears risks of radionecrosis and leucoencephalopathy with neurological and cognitive decline. A solution for this problem could be onetime intraoperative radiotherapy (IORT) with soft x-rays to sterilize the resection cavity, which may provide both: freedom from local recurrence fast track salvage therapy initiation.

INTRAMET is a single institution, open-label, prospective, phase 2 feasibility study for intraoperative radiotherapy immediately following resection of brain metastases. 50 adult patients with resectable not dural brain metastases should be treated in surgery after tumor resection with IORT with 20-30Gy prescribed to the margin of the resection cavity. The highest dose tolerable to surrounding risk structures (N. opticus, brainstem) should be used.

With this method, the investigators hope to show similar local control rates to postoperative external beam radiotherapy in line with guideline recommendations with less patient hospitalization and faster start of rescue therapies which could lead to a favorable overall outcome and less cognitive side effects.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Stefanie Brehmer, MD; Phone Number: +49 621 383 2750; Email: stefanie.brehmer@umm.de

Study Locations

• Germany
  • Mannheim, Germany, 68167
    • Recruiting
    • Universitätsmedizin Mannheim
    • Contact: A
    • Contact: Stefanie Brehmer, MD; Phone Number: +49 621 383 2750; Email: stefanie.brehmer@umm.de
    • Principal Investigator: Stefanie Brehmer, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Karnofsky Performance index ≥ 50%
• MRI T1 Gadolinium enhancing non-dural resectable lesion
• Informed consent
• Adequate birth control
• Frozen section confirms metastasis
• Adequate distance to optic nerve and brainstem

Exclusion Criteria:

• Dural lesions or meningeal carcinomatosis
• Frozen section reveals glioma, lymphoma,small cell lung cancer or germinoma
• Psychiatric or social condition interfering compliance
• Contraindication against anesthesia, surgery, MRI and/or Gadolinium
• Pregnant or breast-feeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intraoperative radiotherapy; After neurosurgical resection and proven metastasis (frozen section) a local intraoperative radiotherapy with soft energy x-rays is applied to the resection cavity. To perform this an applicator is inserted into the situs in the tightest fit rule. The highest possible dose between 30-20 Gy is chosen depending on nearby risk structures (Optic nerve, brainstem) is prescribed. After radiotherapy the applicator is removed and the surgery will be finished in standard way.

Radiation: Intraoperative Radiotherapy; Intraoperative Radiotherapy is performed with a mobile radiation device emitting soft energy x-rays in a spherical way. Different size applicators are available to cover the resection cavity after the tightest fit rule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median local progression-free-survival	Rate of recurrence of the treated lesion in the brain	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall-survival	Survival differentiated between death due to systemic cancer progress and death due to cerebral progress	5 years
Time to further therapy	Time to further cancer therapy (e.g. salvage chemotherapy)	6 month
Patients cognitive performance	Neuropsychological battery	5 years
Patients quality of life	Patient questionary	5 years
Global progression-free-survival	Systemic cancer progression-free-survival	2 years
Regional progression-free-survival	Progression-free survival concerning other brain metastases	2 years
Intraoperative radiotherapy caused dose-limiting toxicities	Occurrence of wound healing disorders or infection requiring surgical revision, cerebral bleeding or ischemia, radionecrosis requiring surgical intervention	6 month after intervention

Collaborators and Investigators

• Sponsor: Universitätsmedizin Mannheim
• Investigators: Principal Investigator: Stefanie Brehmer, MD, Universitätsmedizin Mannheim

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2017
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: July 18, 2017
• First Submitted That Met QC Criteria: July 20, 2017
• First Posted (Actual): July 21, 2017

Study Record Updates

• Last Update Posted (Actual): June 3, 2022
• Last Update Submitted That Met QC Criteria: June 2, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Brain Metastases; Neurosurgery; Intraoperative Radiotherapy
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: 2016-638N-MA

Drug and device information, study documents

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