Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioma

Disease Attributes

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Bevacizumab

Minocycline

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Anti-Bacterial Agents

Patients receiving minocycline 100 mg bid, bevacizumab, and radiation therapy.

Patients receiving minocycline 200 mg bid, bevacizumab, and radiation therapy.

Patients receiving minocycline 400 mg bid, bevacizumab, and radiation therapy.

Bevacizumab will be administered in accordance with the FDA-approved dose for gliomas, 10mg/kg IV every 2 weeks. Bevacizumab will be continued every two weeks as long as tolerated. One cycle of bevacizumab will be 28 days, with treatments on day1 and day 15.

Minocycline will be given by mouth twice a day at the assigned dose level. Minocycline will be started on the day prior to radiation and continued until progression or intolerance.

Radiation planning will be individualized by the radiation oncologist based on the location of the current radiation field relative to prior radiation doses. The length and fractionation will be determined individually by the radiation oncologist.

Radiation

Adam Cohen, MD

The primary objective of step 1 is the rate of adverse events of minocycline and bevacizumab during reirradiation and of step 2 is the response rate to bevacizumab, reirradiation, and minocycline. The secondary objectives are the response rate, Progression Free Survival (PFS)-3, PFS-6, and effects on quality of life and cognition from repeat radiation and bevacizumab.

After providing informed consent, patients will undergo screening for eligibility to participate in the study. Screening will start within 21 days prior to dosing.

Subjects will have an MRI within 21 days of starting radiation. QOL and cognition measures will be performed within 21 days of starting radiation. Radiation will be given with parameters determined on an individual basis by the radiation oncologist. Bevacizumab will be continued at 10mg/kg IV every 2 weeks. Minocycline will be given twice a day starting at 100mg PO bid. MRI, QOL, and cognitive tests will be obtained 1, 3 and 6 months after the end of radiation.

Repeat Radiation, Minocycline and Bevacizumab in Patients With Recurrent Glioma

A Phase 1b/2 Study of Repeat rAdiation, Minocycline, and Bevacizumab in Patients With Recurrent gliOma (RAMBO)

Adverse Events were assessed from start of minocycline treatment (one day prior to start of radiation therapy) until 28 days following the end of radiation therapy. Adverse events were assessed using the Common Terminology for Adverse Events (CTCAE) version 4.0. Each event was assigned a grade (1-5), with lower grades indicating milder events. Events were categorized as severe (grade 3-4) or non-severe (grade 1-2). All adverse events were recorded, regardless of attribution to study treatment. Reported below are the number of patients who experienced any non-severe AE and the number of patients who experienced any severe AE. A full listing of AEs (severe and non-severe) are listed in the Adverse Events module of the Results section.

Proportion of patients who have not progressed 12 weeks after the end of radiation therapy. Radiographic Assessment in Neurooncology (RANO) criteria will be used to assess progression and response. Estimates were done by Kaplan-Meier methods to account for patients whose data was censored prior to progression.

Proportion of patients who have not progressed 26 weeks after the end of radiation therapy. Radiographic Assessment in Neurooncology (RANO) criteria will be used to assess progression and response. Estimates were done by Kaplan-Meier methods to account for patients whose data was censored prior to progression.

Tabulation of the best tumor response participants achieved from baseline through 26 weeks after the end of radiation therapy. Radiographic Assessment in Neurooncology (RANO) criteria will be used to assess progression and response.

The M. D. Anderson Symptom Inventory - Brain Tumors (MDASI-BT) scale was used to assess patients at baseline, 4 weeks post-radiation, 12 weeks post-radiation, and 26 weeks post-radiation. Means and standard deviations from baseline and 26 post-radiation are reported here. MDASI-BT is a 28 item assessment using a 0-10 scale. Part 1 contains 22 items and assesses severity of symptoms, with a score range from 0 to 220. Part 2 contains 6 items and assesses the degree to which symptoms interfere with daily life, with a score range from 0 to 60. The Total score adds Part 1 and Part 2 together to assess total symptom burden, with a score range from 0 to 280. For all parts of the assessment, higher scores indicate a lower quality of life and worse symptom burden.

The Cogstate software was used to assess cognitive function at baseline, 4 weeks post-radiation, 12 weeks post-radiation, and 26 weeks post-radiation. Mean scores and standard deviations from baseline and 26 weeks post-radiation are reported here. Detection Test (DET) measures sensory registration, vigilance, and reaction time. DET is scored based on the speed of performance: mean of the log10 transformed reaction time for correct responses \[measured in log10 milliseconds (MS)\]. Lower scores meant a better performance.

The Cogstate software was used to assess cognitive function at baseline, 4 weeks post-radiation, 12 weeks post-radiation, and 26 weeks post-radiation. Mean scores and standard deviations from baseline and 26 weeks post-radiation are reported here. Identification Test (IDN) measures basic information processing and decision speed. IDN is scored based on the speed of performance: mean of the log10 transformed reaction time for correct responses \[measured in log10 milliseconds (MS)\]. Lower scores meant a better performance.

The Cogstate software was used to assess cognitive function at baseline, 4 weeks post-radiation, 12 weeks post-radiation, and 26 weeks post-radiation. Mean scores and standard deviations from baseline and 26 weeks post-radiation are reported here. One Card Learning Test (OCLT) measures visuoperceptual learning and memory. OCLT is a score defined as the arcsine transformation of the square root of the proportion of correct responses to 80 OCLT questions. The transformed score ranges from 0 to 1.5708 where a higher score means better performance.

The Cogstate software was used to assess cognitive function at baseline, 4 weeks post-radiation, 12 weeks post-radiation, and 26 weeks post-radiation. Mean scores and standard deviations from baseline and 26 weeks post-radiation are reported here. Groton Maze Learning Test (GMLT) measures special learning and executive functioning, including working memory, error monitoring, and ability to integrate feedback to modify problem solving. GMLT score is the number of errors made (lower score indicates better performance).

University of Utah

The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.

Dose Level 0: 100 mg Bid

Dose Level 1: 200 mg Bid

Dose Level 2: 400 mg Bid

Total

Age, Categorical

Age, Continuous

Male

Female

Not Reported

Sex/Gender, Customized

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Josiah Hawks

Any Severe (G3-4) Adverse Event

Any Non-Severe (G1-2) Adverse Event

In dose level 0, three patients were withdrawn prior to completing the reporting period for the primary objective, making them unevaluable, and they were replaced.

Number of Participants With Adverse Events

Patients who did not complete the Dose Limiting Toxicity (DLT) evaluation period (3 patients in Dose Level 0) were excluded from PFS analysis.

Progression Free Survival (PFS) at 3 Months

Patients who did not complete the DLT period (3 patients in Dose Level 0) were excluded from PFS analysis.

Progression Free Survival (PFS) at 6 Months

In Dose Level 0, three patients did not complete any follow-up scans and were excluded from analysis. In Dose Level 2, six patients did not complete any follow-up scans and were excluded from analysis.

Tabulation of Tumor Best Responses

Baseline - Part 1 Score

Baseline - Part 2 Score

Baseline - Total Score

26 Week Post Radiation - Part 1 Score

26 Week Post Radiation - Part 2 Score

26 Week Post Radiation - Total Score

22 patient completed the baseline questionnaire, and 4 patients completed the 26 week post-radiation questionnaire.

Quality of Life Change Over Time

Baseline

26 Weeks Post Radiation

14 patients completed the baseline assessment and 3 patients completed the 26 weeks post radiation therapy assessment. Patients were not required to complete the Cogstate assessment if they took more than one hour to complete it, or if they could not operate a computer or if they could not complete the practice tests.

Cognitive Change Over Time - DET

16 patients completed the baseline assessment and 3 patients completed the 26 weeks post radiation therapy assessment. Patients were not required to complete the Cogstate assessment if they took more than one hour to complete it, or if they could not operate a computer or if they could not complete the practice tests.

Spots Global Cancer Trial Database for Repeat Radiation, Minocycline and Bevacizumab in Patients With Recurrent Glioma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial