Minocycline Therapy for Management of Adverse Radiation Effects

• Status: Terminated
• Trial end date: 2018-05-31
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Pittsburgh
• Treatments: Minocycline

Criteria

Inclusion Criteria:

• Age range: 18 - 90 years

• Males and females.

• Patients must have undergone cranial radiosurgery.

• MRI evidence supporting the diagnosis of ARE and/or surgical biopsy evidence of necrosis without tumor at ≤2 months before study entry.

• Karnofsky performance status of ≥60,

• With or without evidence of progressive neurologic signs or symptoms appropriate to the location of the ARE, and no previous bevacizumab therapy.

• With or without previous chemotherapy for their tumor.

• Routine laboratory study results with bilirubin ≤1.5 times the upper limit of normal, aspartate aminotransferase and/or alanine aminotransferase <2.5 times the upper limit of normal, creatinine <2.0 times the upper limit of normal.

• Patients with a history of seizures will be required to be receiving anticonvulsant therapy and to be seizure-free for ≥1 week before study.

Exclusion Criteria:

• Significant mass effect requiring resection (as assessed by a clinical neurosurgeon)

• Known hypersensitivity to tetracyclines

• Women of childbearing age must be non-lactating and have a negative urine pregnancy test (adequate birth control includes use of intra uterine device, or a barrier method, e.g. condom, diaphragm). The results of animal studies indicate that tetracyclines cross the placenta and are found in fetal tissues, having potentially toxic effects on the developing fetus (often related to retardation of skeletal development). Evidence of embryo toxicity has been noted in animals treated early in pregnancy. Therefore pregnant women will not be allowed to participate in this study

• Female subjects on oral contraceptives

• Contraindication to undergo MRI

• Significant cardiopulmonary, renal or neurological co-morbidities

• Current diagnosis of major depression, substance abuse, or other psychiatric disorders;