Stereotactic Radiotherapy of the Resection Cavity of Brain Metastases vs. Post-operative Whole-brain Radiotherapy

NCT03285932 | Completed Phase 2 DMC

• 1 other identifier: ESTRON
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

In advanced cancer disease brain metastases are common, difficult to treat, and are associated with a poor prognosis. As new local and systemic therapies are eventually resulting in improved survival and quality of life for patients with brain metastases, negative neurocognitive effects of radiation therapy are becoming increasingly important as well as good loco-regional disease control of brain metastases. Concerning treatment, brain metastases remain a major clinical problem and a multidisciplinary approach to management should be adopted. Neurosurgical resection with postoperative whole brain radiotherapy (WBRT) is one major treatment option in solitary or symptomatic brain metastases. Furthermore, WBRT is recommended for multiple brain metastases. For a limited number of brain metastases stereotactic radiosurgery (SRS) has been established as a highly effective treatment alternative. Recently, a new treatment approach combing neurosurgery with postoperative stereotactic radiotherapy (SRT) of the resection cavity is emerging. Based on available evidence, postoperative SRT of the resection cavity improves local control following surgery, reduces the number of patients who require whole brain radiotherapy, and is well tolerated (1). This protocol is aimed at primarily evaluating the safety and toxicity profile of SRT to the resection cavity following neurosurgical resection combined with SRT of potentially further unresected brain metastases, compared to postoperative whole-brain radiotherapy (WBRT). Secondary, the local effect of SRT in patients with brain metastases will be assessed by measuring time to local recurrence (LR), local and loco-regional progression-free survival (PFS). Additional systemic treatment will be carried out according to the standards of the National Center for Tumor Therapy (NCT).

Conditions

Brain Metastases, Adult

Keywords

Brain Metastase; Radiation of resection cavity; WBRT (whole brain radiotherapy); SRS (stereotactic radiosurgery)

Outcome Measures

Primary Outcomes (1)

• neurological progression-free survival (PFS)

  Neurologic progression-free survival in follow-up imaging is the primary endpoint of the study. The duration is defined as the time interval between the date start of RT and the date of local and loco-regional progression or death, or the date of leaving the study without local and loco-regional progression (e.g., lost to follow up non-local progression) whatever occurs first. Patients not reported local and loco-regional progressive or dead, or lost to follow-up or non-local progressive will be censored at the date of the last follow-up examination where no signs of local and loco-regional progression were observed.

  12 months PFS rate

Secondary Outcomes (7)

• Overall survival (OS)

  12 months survival rate

• Local PFS

  12 months after treatment

• Quality of life (QLQ-C30)

  up to 12 months after treatment

• Loco-regional recurrence

  up to 12 months after treatment

• Quality of life (BN20)

  up to 12 months after treatment

Study Arms (2)

Post-operative SRS of resection cavity

EXPERIMENTAL

High-resolution contrast-enhanced post-operative MRI imaging in preparation for Cyberknife SRS. Cyberknife SRS of the resection cavity and all potential additional metastases diagnosed in the treatment planning MRI (up to 10 lesions) Resection cavity: 7 x 5 Gy @ 95%-isodose Potential additional brain metastases: 20 Gy @ 70%-isodose (lesions \< 2 cm max. diameter) 18 Gy @ 70%-isodose (lesions 2 - 3 cm max. diameter) 6 x 5 Gy @ 70%-isodose (lesions \> 3 cm max. diameter)

Radiation: post-operative stereotactic radiosurgery (SRS)

Post-operative WBRT

OTHER

Post-operative WBRT will be performed according to the following dose regimen: 10 x 3 Gy

Radiation: Whole brain radiotherapy (WBRT)

Interventions

post-operative stereotactic radiosurgery (SRS) RADIATION

For radiosurgery, patients will be immobilized. Treatment planning including the MRI and planning CT should be performed 1 -2 weeks before SRT and treatment finished at latest 3-4 weeks after surgery. Planning should be as close to SRT as possible. Organs at risk such as the brain stem, optic nerves, chiasm and spinal cord will be contoured. The Clinical Target Volume 1 (CTV1) will be defined as the resection cavity based on MRI and CT including T1 contrast enhanced changes around the resection cavity. The Clinical Target Volume 2 (CTV2) will be defined as a 3mm margin added to CTV1 by isotropic expansion and slightly adjusted as deemed appropriated by the experienced contouring physician. The Planning Target Volume (PTV) will be an additional margin of 1mm added to CTV2 by isotropic expansion. Treatment planning will be performed using Accuray's Multiplan or subsequent approved treatment planning systems for Cyberknife.

Post-operative SRS of resection cavity

Whole brain radiotherapy (WBRT) RADIATION

For WBRT, an individual head fixation mask is manufactured for each patient, and treatment planning is performed as virtual simulation or 3D-conformal RT planning based on CT-imaging. The portals include the whole brain with special focus as including the skull base areas and lamina cribrosa. For low infratentorial lesions, the treatment volume may include the whole brain down to the second cervical vertbra. RT will be applied with two portals (e.g. 87°and 273°) using a 6 MeV linear accelerator. For WBRT, a total dose of 30 Gy in 3 Gy fractions will be applied.

Post-operative WBRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• histologically confirmed solid cancer
• MRI confirmed cerebral metastases
• Neurosurgical resection of one cerebral metastasis
• age ≥ 18 years of age
• Karnofsky Performance Score \>60
• for women with childbearing potential, (and men) adequate contraception.
• ability to understand character and individual consequences of the clinical trial
• written informed consent (must be available before enrolment in the trial)

You may not qualify if:

• refusal of the patients to take part in the study
• previous radiotherapy to the brain
• \> 10 unresected brain metastases in postoperative MRI
• Patients who have not yet recovered from acute toxicities of prior therapies
• known carcinoma \< 2 years ago (excluding carcinoma in situ of the cervix, basal cell carcinoma, squamous cell carcinoma of the skin) requiring immediate treatment interfering with study therapy
• pregnant or lactating women

Sponsors & Collaborators

• Juergen Debus: lead
• Heidelberg University: collaborator

Study Sites (1)

Department of Radiotherapy, University of Heidelberg

Heidelberg, 69120, Germany

Location

Related Publications (21)

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MeSH Terms

Conditions

Brain Neoplasms; Snyder Robinson syndrome

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Juergen Debus, Prof. Dr. Dr.

  Head of department Radiation Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. Dr. Jürgen Debus

Study Record Dates

• First Submitted: September 13, 2017
• First Posted: September 18, 2017
• Study Start: February 1, 2018
• Primary Completion: May 30, 2021
• Study Completion: July 8, 2021
• Last Updated: November 3, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)