Irradiation; Adverse Effect Clinical Trial
Official title:
A Safety and Feasibility Study of Minocycline Therapy for Management of Adverse Radiation Effects After Brain Metastases Radiosurgery
Stereotactic radiosurgery (SRS) is a well-established treatment for patients with metastatic
brain tumors. Although SRS has a very high tumor growth control these interventions are
associated with adverse radiation effects (ARE) in approximately 15 % of patients. The
traditional approach, and still a mainstay, is the administration of a course of high dose
anti-inflammatory corticosteroids. Currently there are no other effective oral
neuroprotective agents in clinical practice which can improve outcomes of patients with ARE
after radiosurgery for brain metastases.
Minocycline, an antibiotic with a favorable adverse effect profile and pharmacokinetics, has
been shown to have neuroprotective properties in experimental models of a variety of
neurological diseases, as well as in human clinical trials. The investigators propose a
single arm clinical trial, to evaluate the safety and feasibility of minocycline in improving
ARE. This study will recruit 15 patients who will be treated with minocycline (100mg BID) for
3 months. This clinical trial has the potential to prove that minocycline therapy is safe in
this patient population. In addition, positive results will provide preliminary evidence for
its use in an array of radiosurgical indications.
Although stereotactic radiosurgery (SRS) has proven to be highly effective in the management
of brain metastases, it is not without risk. Despite selective targeting of lesions and the
sharp dose fall-off associated with radiosurgical treatments, adverse radiation effects
(AREs) can occur in 10-15% of patients. Adverse radiation effects (AREs) can be defined as
unexpected or undesirable post-radiosurgery imaging change regardless of whether it is
clinically symptomatic. Patients showing ARE have limited therapeutic options with
corticosteroids being the main treatment modality. This single arm clinical trial, will
evaluate the safety and feasibility of minocycline in improving AREs. Brain metastases
patients with documented AREs will be treated with minocycline (100 mg twice a day) for 3
months in addition to the standard treatment with oral corticosteroids. The investigators
anticipate recruiting a total of 15 patients over 12 months.
Primary aim:
The primary aim is of this study to evaluate safety and feasibility of minocycline therapy in
patients with ARE after radiosurgery. The investigators' hypothesis is that minocycline will
be safe in this patient population. Safety will be assessed by monitoring blood levels of
drug, liver enzymes, renal function tests, and monitoring for major and minor side-effects.
Research Strategy The investigators plan to conduct a single arm observational study to
evaluate safety and feasibility of minocycline in patients diagnosed with radiosurgery
associated adverse radiation effects. In addition to clinical and biochemical monitoring for
safety, the investigators will also employ neuroimaging techniques to investigate whether
minocycline reduces enhancement at lesion in post contrast T1 weighted MRI and reduces hyper
intensity surrounding the tumor as detected by T2 MRI radiosurgery.
Primary Outcomes: 1) The primary clinical outcome will be safety of minocycline use in this
patient population.
Secondary outcomes: 1) The investigators will also review brain images in detail to find any
evidence of benefit from Minocycline therapy such as reduction or resolution of volume of T2
hyper intensity and contrast enhancement at the lesion (radiation necrosis) at 4-6 weeks and
3 month follow-up. 2) Overall neurological status 3) Change in neurocognitive status, 4)
Reduction in the number of patients needing resection 5) Changes in plasma biomarkers, and
plasma drug levels.
Target Population: Recruitment will take place at Center of Image-guided Neurosurgery of
UPMC. All patients with AREs after brain metastases radiosurgery will be potentially eligible
for the study. The investigators anticipate enrolling 15 patients. Patients will be diagnosed
based on MRI findings. The investigators will evaluate T1 pre and post contrast, T2, FLAIR
and Perfusion MR in order to diagnose ARE. MR spectroscopy or CT Pet will be obtained when
clinically indicated. The investigators will use T1/T2 matching and proportion of edema
versus lesion volume as a guide for diagnosing ARE.
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