Recurrent GliomaPhase 1/2RAMBONCT01580969
Repeat Radiation, Minocycline and Bevacizumab in Patients With Recurrent Glioma
A Phase 1/2 study testing Bevacizumab, Minocycline and Radiation in people with Recurrent Glioma, run by University of Utah at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Glioma
- What is being tested?
- Bevacizumab, Minocycline and Radiation
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Jul 2012to 15 May 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients ≥18 years old with a life expectancy of at least 8 weeks
- Radiographically proven recurrent (≥ first relapse), intracranial glioma
- Previous treatment with external beam radiation
- Radiographic progression on current or prior bevacizumab treatment
- Women of child-bearing potential must have a negative pregnancy test within 7 days of initiation of dosing and must agree to use an acceptable method of birth control while on study drug and for 3 months after the last dose. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥1 year. Men of child-bearing potential must also agree to use an acceptable method of birth control while on study drug, and for 3 months after the last dose.
- Karnofsky performance status of ≥50
Show all 11Show fewer
- Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥1.0 x 109/L, Hgb >9 g/dL, platelet count ≥50 x 109/L, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤2.5x ULN, creatinine ≤1.5x ULN)
- Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements
- Systolic blood pressure ≤ 160 mg Hg or diastolic pressure ≤ 90 mg Hg within 14 days prior to study registration
- Prothrombin time/international normalized ratio (PT INR) < 1.4 for patients not on warfarin confirmed by testing within 14 days prior to study registration
- Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight (LMW) heparin) must have no active bleeding or pathological condition that carries a high risk of bleeding, and must be on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
Who cannot join
- Use of an investigational drug within 14 days or within 5 half-lives of teh investigational drug, whichever is shorter
- Progression within 3 months of previous radiation by Radiographic Assessment in Neurooncology (RANO) criteria
- History of Grade 2 (CTCAE v4) or greater acute intracranial hemorrhage
- A concurrent active cancer that requires non-surgical therapy (e.g. chemotherapy, radiation, adjuvant therapy).
- Patients with serious illnesses, uncontrolled infection, medical conditions, or other medical history including abnormal laboratory results, which in the investigator's opinion would be likely to interfere with a patient's participation in the study, or with the interpretation of the results
- Women of child-bearing potential who are pregnant or breast feeding
Show all 11Show fewer
- Unstable angina and/or congestive heart failure in the last 6 months, transmural myocardial infarction within the last 6 months, New York Heart Association grade II or higher congestive heart failure requiring hospitalization within 12 months prior to registration, evidence of recent myocardial infarction by EKG performed within 14 days of registration, serious or inadequately controlled cardiac arrhythmia, significant vascular and peripheral vascular disease, evidence of bleeding diathesis or coagulopathy
- History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months
- Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration, with the exception of the craniotomy for tumor resection
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
- Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity
Trial locations and contacts
1 site in 1 country.
United States1 site
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
About this study
Official title: A Phase 1b/2 Study of Repeat rAdiation, Minocycline, and Bevacizumab in Patients With Recurrent gliOma (RAMBO)
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.
Read the detailed description
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.
- Conditions
- Recurrent Glioma
- Being tested
- Bevacizumab, Minocycline, Radiation
- Keywords
- glioma
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin
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.
MinocyclineDrug
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.
RadiationRadiation
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.
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 0: 100 mg bid | Experimental | Patients receiving minocycline 100 mg bid, bevacizumab, and radiation therapy. Receives: Drug: Bevacizumab; Drug: Minocycline; Radiation: Radiation |
| Dose Level 1: 200 mg bid | Experimental | Patients receiving minocycline 200 mg bid, bevacizumab, and radiation therapy. Receives: Drug: Bevacizumab; Drug: Minocycline; Radiation: Radiation |
| Dose Level 2: 400 mg bid | Experimental | Patients receiving minocycline 400 mg bid, bevacizumab, and radiation therapy. Receives: Drug: Bevacizumab; Drug: Minocycline; Radiation: Radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
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.
Measured: From first dose of study treatment to 28 days following radiation therapy (7-8 weeks)
Secondary outcomes (8)
Progression Free Survival (PFS) at 3 Months
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.
Measured: From start of study treatment until 12 weeks after radiation therapy (15-16 weeks)
Progression Free Survival (PFS) at 6 Months
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.
Measured: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Tabulation of Tumor Best Responses
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.
Measured: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Quality of Life Change Over Time
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.
Measured: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Cognitive Change Over Time - DET
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.
Measured: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Cognitive Change Over Time - IDN
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.
Measured: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Cognitive Change Over Time - OCLT
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.
Measured: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Cognitive Change Over Time - GMLT
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).
Measured: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2012 (estimated)
- Study start6 Jul 2012
- Primary completion12 Jan 2018
- Study completion15 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Recurrent GliomaStudies of the same condition, open and under way.
- More trials run by University of UtahThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Adam Cohen, MD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01580969
- Sponsor's protocol ID
- HCI55264
- Acronym
- RAMBO
- Status last verified
- Aug 2019
- First submitted
- 6 Mar 2012
- Last updated
- 16 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2 Study of Repeat rAdiation, Minocycline, and Bevacizumab in Patients With Recurrent gliOma (RAMBO)
- ClinicalTrials.gov ID
- NCT01580969
- Acronym / sponsor ID
- RAMBO / HCI55264
- Conditions
- Recurrent Glioma
- Keywords
- glioma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Study start
- 6 Jul 2012 (actual)
- Primary completion
- 12 Jan 2018 (actual)
- Study completion
- 15 May 2018 (actual)
- First posted
- 19 Apr 2012 (estimated)
- Results
- Posted 6 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose Level 0: 100 mg bid | Experimental | Drug: Bevacizumab, Drug: Minocycline, Radiation: RadiationPatients receiving minocycline 100 mg bid, bevacizumab, and radiation therapy. |
| Dose Level 1: 200 mg bid | Experimental | Drug: Bevacizumab, Drug: Minocycline, Radiation: RadiationPatients receiving minocycline 200 mg bid, bevacizumab, and radiation therapy. |
| Dose Level 2: 400 mg bid | Experimental | Drug: Bevacizumab, Drug: Minocycline, Radiation: RadiationPatients receiving minocycline 400 mg bid, bevacizumab, and radiation therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male or female patients ≥18 years old with a life expectancy of at least 8 weeks
- Radiographically proven recurrent (≥ first relapse), intracranial glioma
- Previous treatment with external beam radiation
- Radiographic progression on current or prior bevacizumab treatment
- Women of child-bearing potential must have a negative pregnancy test within 7 days of initiation of dosing and must agree to use an acceptable method of birth control while on study drug and for 3 months after the last dose. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥1 year. Men of child-bearing potential must also agree to use an acceptable method of birth control while on study drug, and for 3 months after the last dose.
Key exclusion criteria (11 listed)
- Use of an investigational drug within 14 days or within 5 half-lives of teh investigational drug, whichever is shorter
- Progression within 3 months of previous radiation by Radiographic Assessment in Neurooncology (RANO) criteria
- History of Grade 2 (CTCAE v4) or greater acute intracranial hemorrhage
- A concurrent active cancer that requires non-surgical therapy (e.g. chemotherapy, radiation, adjuvant therapy).
- Patients with serious illnesses, uncontrolled infection, medical conditions, or other medical history including abnormal laboratory results, which in the investigator's opinion would be likely to interfere with a patient's participation in the study, or with the interpretation of the results
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 |
|---|---|---|
| BevacizumabAlso: AvastinBevacizumab 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. | Drug | Dose Level 0: 100 mg bid, Dose Level 1: 200 mg bid, Dose Level 2: 400 mg bid |
| MinocyclineMinocycline 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. | Drug | Dose Level 0: 100 mg bid, Dose Level 1: 200 mg bid, Dose Level 2: 400 mg bid |
| RadiationRadiation 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 | Dose Level 0: 100 mg bid, Dose Level 1: 200 mg bid, Dose Level 2: 400 mg bid |
Primary outcome
Number of Participants With Adverse Events
Time frame: From first dose of study treatment to 28 days following radiation therapy (7-8 weeks)
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.
8 secondary outcomes
Progression Free Survival (PFS) at 3 Months
Time frame: From start of study treatment until 12 weeks after radiation therapy (15-16 weeks)
Progression Free Survival (PFS) at 6 Months
Time frame: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Tabulation of Tumor Best Responses
Time frame: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Quality of Life Change Over Time
Time frame: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Cognitive Change Over Time - DET
Time frame: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Cognitive Change Over Time - IDN
Time frame: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Cognitive Change Over Time - OCLT
Time frame: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Cognitive Change Over Time - GMLT
Time frame: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Recurrent Glioma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma
RecruitingObservational study
Collection of Blood and Urine Samples in Patients Receiving Radiation Therapy for Glioblastoma Multiforme
Glioblastoma Multiforme
Active, not recruitingPhase 3
Sonocloud-9 in Association With Carboplatin Versus Standard-of-Care Chemotherapies (CCNU or TMZ) in Recurrent GBM
Glioblastoma, Recurrent Glioblastoma
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.
Adam Cohen, MD principal investigator
University of Utah
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bevacizumab, Minocycline and Radiation in people with Recurrent Glioma, run by University of Utah 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 11 inclusion and 11 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: finished, as of the sponsor's last update on 16 Aug 2019. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Adverse Events (time frame: From first dose of study treatment to 28 days following radiation therapy (7-8 weeks)). 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 16 Aug 2019.