Minocycline Therapy for Management of Adverse Radiation Effects

NCT02201563 | Terminated Phase 1

• 1 other identifier: PRO14020381
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Irradiation; Adverse Effect

Keywords

Adverse radiation effects (ARE); Radiosurgery; Brain metastases; Minocycline

Outcome Measures

Primary Outcomes (1)

• Monitoring for adverse effects of Minocycline

  Safety will be assessed by monitoring blood levels of drug, liver enzymes, renal function tests, and monitoring for major and minor side-effects.

  3 months

Secondary Outcomes (1)

• Monitoring for imaging improvement

  3 months

Study Arms (1)

Minocycline

EXPERIMENTAL

oral Minocycline 100 mg twice a day for 3 months.

Drug: Minocycline

Interventions

Minocycline DRUG

Oral minocycline (100mg twice a day) for 3 months

Also known as: Dynacin, Minocin, Minocin PAC, Myrac, Solodyn, Vectrin

Minocycline

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• University of Pittsburgh: lead

Study Sites (1)

UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; cyclopia sequence

Interventions

Minocycline

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Ajay Niranjan, MD, MBA

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 24, 2014
• First Posted: July 28, 2014
• Study Start: November 1, 2015
• Primary Completion: May 31, 2018
• Study Completion: May 31, 2018
• Last Updated: June 25, 2018

Record last verified: 2018-06

Locations

US (1)