Irradiation; Adverse EffectPhase 1NCT02201563
Minocycline Therapy for Management of Adverse Radiation Effects
A Phase 1 study testing Minocycline in people with Irradiation; Adverse Effect, run by University of Pittsburgh at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Irradiation; Adverse Effect
- What is being tested?
- Minocycline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2015to 31 May 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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;
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Irradiation; Adverse Effect
- Being tested
- Minocycline
- Keywords
- Adverse radiation effects (ARE), Radiosurgery, Brain metastases, Minocycline
- Medical subject headings
- Brain Neoplasms, cyclopia sequence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MinocyclineDrug
Also called Dynacin, Minocin, Minocin PAC, Myrac, Solodyn, Vectrin
Oral minocycline (100mg twice a day) for 3 months
| Study group | Role | What they receive |
|---|---|---|
| Minocycline | Experimental | oral Minocycline 100 mg twice a day for 3 months. Receives: Drug: Minocycline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 months
Secondary outcomes (1)
Monitoring for imaging improvement
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.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2014 (estimated)
- Study startNov 2015
- Primary completion31 May 2018
- Study completion31 May 2018
Why it stopped: Very slow recruitment (only one patient was recruited)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Irradiation; Adverse EffectStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ajay Niranjan, University of Pittsburgh
- Investigators
- Ajay Niranjan, MD, MBA, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02201563
- Sponsor's protocol ID
- PRO14020381
- Status last verified
- Jun 2018
- First submitted
- 24 Jul 2014
- Last updated
- 25 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety and Feasibility Study of Minocycline Therapy for Management of Adverse Radiation Effects After Brain Metastases Radiosurgery
- ClinicalTrials.gov ID
- NCT02201563
- Acronym / sponsor ID
- PRO14020381
- Conditions
- Irradiation; Adverse Effect
- Keywords
- Adverse radiation effects (ARE), Radiosurgery, Brain metastases, Minocycline
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Very slow recruitment (only one patient was recruited)
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Study start
- Nov 2015
- Primary completion
- 31 May 2018 (actual)
- Study completion
- 31 May 2018 (actual)
- First posted
- 28 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Minocycline | Experimental | Drug: Minocyclineoral Minocycline 100 mg twice a day for 3 months. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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,
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MinocyclineAlso: Dynacin, Minocin, Minocin PAC, Myrac, Solodyn, VectrinOral minocycline (100mg twice a day) for 3 months | Drug | Minocycline |
Primary outcome
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.
1 secondary outcome
Monitoring for imaging improvement
Time frame: 3 months
Results and safety
The study was stopped early (reason given: Very slow recruitment (only one patient was recruited)). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ajay Niranjan, MD, MBA principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Minocycline in people with Irradiation; Adverse Effect, run by University of Pittsburgh at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Very slow recruitment (only one patient was recruited)). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Monitoring for adverse effects of Minocycline (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2018.