We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Minocycline Therapy for Management of Adverse Radiation Effects

This study is currently recruiting participants.
Verified June 2017 by Ajay Niranjan, University of Pittsburgh
Sponsor:
ClinicalTrials.gov Identifier:
NCT02201563
First Posted: July 28, 2014
Last Update Posted: June 21, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Ajay Niranjan, University of Pittsburgh
  Purpose

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.


Condition Intervention Phase
Irradiation; Adverse Effect Drug: Minocycline Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Safety and Feasibility Study of Minocycline Therapy for Management of Adverse Radiation Effects After Brain Metastases Radiosurgery

Resource links provided by NLM:


Further study details as provided by Ajay Niranjan, University of Pittsburgh:

Primary Outcome Measures:
  • Monitoring for adverse effects of Minocycline [ Time Frame: 3 months ]
    Safety will be assessed by monitoring blood levels of drug, liver enzymes, renal function tests, and monitoring for major and minor side-effects.


Secondary Outcome Measures:
  • Monitoring for imaging improvement [ Time Frame: 3 months ]
    Brain MRIs will be performed 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.


Estimated Enrollment: 15
Study Start Date: November 2015
Estimated Study Completion Date: September 30, 2018
Estimated Primary Completion Date: June 30, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Minocycline
oral Minocycline 100 mg twice a day for 3 months.
Drug: Minocycline
Oral minocycline (100mg twice a day) for 3 months
Other Name: Dynacin, Minocin, Minocin PAC, Myrac, Solodyn, Vectrin

Detailed Description:

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 90 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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;
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02201563


Contacts
Contact: Ajay Niranjan, MD, MBA 412-647-6781 niranjana@upmc.edu
Contact: Edward Monaco, MD, PhD 412-647-6782 monacoea2@upmc.edu

Locations
United States, Pennsylvania
UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Principal Investigator: Ajay Niranjan, MD, MBA         
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Ajay Niranjan, MD, MBA University of Pittsburgh
  More Information

Responsible Party: Ajay Niranjan, Associate Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02201563     History of Changes
Other Study ID Numbers: PRO14020381
First Submitted: July 24, 2014
First Posted: July 28, 2014
Last Update Posted: June 21, 2017
Last Verified: June 2017

Keywords provided by Ajay Niranjan, University of Pittsburgh:
Adverse radiation effects (ARE)
Radiosurgery
Brain metastases
Minocycline

Additional relevant MeSH terms:
Minocycline
Anti-Bacterial Agents
Anti-Infective Agents