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Stereotactic Radiosurgery for Brain Metastases


Title A Phase III Trial Of Stereotactic Radiosurgery Compared With Whole Brain Radiotherapy (WBRT) For 5-15 Brain Metastases
Therapeutic Area Brain Tumors, Breast Cancer
Principal Investigator John Mignano, MD
Min Age 18 Years
Gender All
Contact Erica Holt
617-636-2675
More Information https://www.clinicaltrials.gov/ct2/show/NCT03550391

Overview

This is an international multi-centre, open-label, randomized phase III trial comparing stereotactic radiosurgery (SRS) to whole brain radiotherapy (WBRT) in patients with 5 to 15 brain metastases.

Primary Objectives

• To compare the overall survival in patients with five to fifteen brain metastases who receive SRS compared to patients who receive WBRT.

• To compare the neurocognitive progression-free survival in patients with five to fifteen brain metastases who receive SRS compared to patients who receive WBRT.

 

Secondary Objectives

Patient/treatment Related Secondary Outcomes

• To compare time to central nervous system (CNS) failure (local, distant, and leptomeningeal) in patients who receive SRS compared to patients who receive WBRT.

• To evaluate if there is any difference in CNS failure patterns (local, distant, or leptomeningeal) in patients who receive SRS compared to patients who receive WBRT.

• To evaluate number of salvage procedures following SRS in comparison to WBRT.

• To evaluate the individual cognitive test results following SRS in comparison to WBRT.

• To tabulate and descriptively compare the post-treatment adverse events associated with the interventions.

• To evaluate the time delay to (re-)initiation of systemic therapy in patients receiving SRS in comparison to WBRT.

• To prospectively validate a predictive nomogram for distant brain failure [Ayala-Peacock 2014].

Economic Endpoints

• To compare the estimated cost of brain-related therapies in patients who receive SRS compared to patients who receive WBRT:

- Comparison based on payer rates (Medicare for US / provincial heath authorities in Canadian jurisdictions with activity-based funding).

Quality of Life Endpoints

• To evaluate patient’s quality of life, as assessed by the EORTC QLQ-C30 + BN20, EQ-5D, ECOG performance status, for those who receive SRS compared to those who receive WBRT.

Translational Endpoints

• Collect plasma to evaluate whether detectable somatic mutations in liquid biopsy can enhance prediction of the overall survival and development of new brain metastases.

• Analysis of serum samples for inflammatory biomarker C-reactive protein and brain-derived-neurotrophic factor (BDNF) to elucidate molecular/genomic mechanisms of neurocognitive decline and associated radiographic changes.

Imaging/Dosimetric Endpoints

• Collect whole-brain dosimetry in SRS patients to be prospectively correlated with cognitive toxicity, intracranial control and radiation necrosis (hippocampal dosimetry will be retrospectively assessed).

• Collect imaging parameters and workflow details relating to the radiosurgery planning MRIs (including timing of MR prior to radiosurgery, magnet field strength, contrast type/dose/timing, use of image post-processing, and formal reviewed by radiology) to be prospectively correlated with tumour control outcomes (local control, intracranial control).

• Evaluate serial changes in imaging features found in routine MRI images (T2w changes, morphometry) that may predict tumour control and/or neurocognitive outcomes

Study Details

Inclusion Criteria

  • Patients must have 5 or more brain metastases as counted on a T1 contrast enhanced MRI obtained ≤ 30 days from randomization (maximum 15 brain metastases).
  • Patients must have a pathological diagnosis (cytological or histological) of a non-hematopoietic malignancy.
  • The largest brain metastasis must measure <2.5 cm in maximal diameter. The total tumour volume must be 30 cm3 or less. Lesion volume will be approximated by measuring the lesion’s three perpendicular diameters on contrast-enhanced, T1-weighted MRI and the product of those diameters will be divided by 2 to estimate the lesion volume (e.g. xyz/2). Alternatively, direct volumetric measurements via slice by slice contouring on a treatment planning software package can be used to calculate the total tumour volume.

Exclusion Criteria

  • Pregnant or nursing women.
  • Inability to complete a brain MRI.
  • Known allergy to gadolinium.

Study Requirements

7 research visits on top of randomized protocol treatment over a total of 24 months with annual follow-up until disease progression.