Randomized Phase II Study: Corticosteroids + Bevacizumab vs. Corticosteroids + Placebo (BeSt) for Radionecrosis after Radiosurgery for Brain Metastases.
This randomized phase II study aims to investigate whether the addition of bevacizumab to standard corticosteroid therapy results in greater improvement in symptoms and less treatment-induced symptoms compared with standard corticosteroid therapy for patients with symptomatic brain radionecrosis following radiosurgery. It is hypothesized that the addition of bevacizumab to standard care corticosteroids will reduce treatment-induced toxicities and improve neurologic impairments in patients with brain radionecrosis following radiosurgery for brain metastases.
Registration/Randomization Eligibility Criteria:
* A diagnosis of radionecrosis will be based on a clinical onset of symptoms and radiological findings of radionecrosis at 3-24 months following radiosurgery, with or without pathological confirmation. 1.1 'Symptomatic' brain radionecrosis to at least one lesion following radiosurgery treatment for brain metastases where 'symptomatic' is defined as: 1.1.1 New or increasing headache associated with mass effect, sensory or motor abnormality, cognitive changes, speech difficulty, balance or coordination difficulty, cranial nerve deficits 1.1.2 Symptoms are persistent or worsening despite administration of at least dexamethasone 4 mg daily for 1 week 1.2 Clinical eligibility supported by central imaging real-time review. The presence of at least the following conventional MR image characteristic: 1.2.1 Conventional MR - Lesion quotient of < 0.3, where lesion quotient is defined as the proportional value of the maximum axial cross-sectional area of the T2-weighted defined lesion over the maximum axial cross-sectional area of the contrast-enhancing lesion on the T1-weighted post-gadolinium sequence on a comparable axial slice. If the conventional MR findings are not seen, the following dynamic susceptibility-contrast (DSC) MR characteristics may be used to meet eligibility for this study. 1.2.2 DSC MR - The cut-offs below will be based on GRE EPI DSC perfusion images, acquired without using a gadolinium pre-load: 18.104.22.168 Relative cerebral blood volume (rCBV) <1.5 in the enhancing- lesion relative to normal-appearing white matter (NAWM) 22.214.171.124. Percentage of signal recovery (PSR) > 76%, where PSR is determined by comparing the lower signal intensity during passage of the contrast bolus with the post-contrast signal intensity on the signal intensity-time curve 1.2.3 Centers that standardly use PET or MRS to determine a diagnosis of radionecrosis are permitted to use these modalities to assist in their patient selection; however the criteria described for conventional MR and/or DSC should also be met for study eligibility. Both PET and MRS are not mandatory for study eligibility.
* Prior to start of treatment 2.1 Must have been taking a stable dose of corticosteroids for symptom management for at least 1 week before baseline MRI. 2.2 No systemic therapy within 2 weeks prior to registration or plan for systemic therapy within the first 8 weeks after study registration. The protocol provides a list of 'approved systemic' therapies that are allowed for concurrent use with bevacizumab. 2.3 No bevacizumab ≤ 3 months of study registration. 2.4 Central imaging real-time review (72 hour turn around) to confirm eligibility.
Alison Conlin, M.D.
The Pacific Cancer Research Consortium clinical trials are offered at multiple locations throughout Oregon, Washington, Alaska, California, and Idaho. To find a location near you, please contact the Patient Engagement Center at 844-552-2734.