Malignant GliomaNCT01017250
Radiosurgery and Avastin for Recurrent Malignant Gliomas
A study testing Stereotactic Radiosurgery (SRS) and Bevacizumab in people with Malignant Glioma, run by Duke University at 1 site in United States.
Trial summary
The purpose of this study is to assess the central nervous system (CNS) toxicity in patients with recurrent malignant gliomas treated with concurrent Avastin and stereotactic radiosurgery (SRS). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Malignant Glioma
- What is being tested?
- Stereotactic Radiosurgery (SRS) and Bevacizumab
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2009to Feb 2012
- Phase
- Interventional
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- History of malignant glioma (WHO Grade III or IV) of the brain treated with some combination of surgery, biochemotherapy and conventionally fractionated external beam radiotherapy
- Radiotherapy completed at least 6 months prior to recurrence
- Age 18 years and older
- New or enlarging contrast-enhancing and/or 18FDG-avid nodule, at least 1 cm diameter
- Estimated life expectancy of 3 months or longer
Who cannot join
- Avastin therapy within 21 days of start of participation
- Contraindication to Avastin therapy or brain MRI
- Presence of bleeding diathesis or coagulopathy
- History of prior arterial thrombotic event, myocardial infarction, angina, CVA, TIA, CABG angioplasty or stenting within 6 months.
- Inadequately controlled hypertension (defined as systolic blood pressure
- New York Heart Association (NYHA) Grade II or greater congestive heart failure
Show all 13Show fewer
- Clinically significant vascular disease
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to onset of treatment
- Prior history of hypertensive crisis or hypertensive encephalopathy
- History of abdominal fistula or GI perforation within 6 months prior to onset of treatment
- Serious non-healing wound, active ulcer or untreated bone fracture
- Proteinuria demonstrated by Urine Protein Creatinine ratio > 1.0
- Pregnancy
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center, Radiation Oncology
Durham, North Carolina, 27710
About this study
The purpose of this study is to assess the central nervous system (CNS) toxicity in patients with recurrent malignant gliomas treated with concurrent Avastin and stereotactic radiosurgery (SRS).
Read the detailed description
In this pilot study, 15 human subjects with recurrent, unifocal malignant gliomas up to 5-cm in maximum dimension no longer responding to conventional chemotherapy but able to tolerate further chemotherapy will be enrolled. The primary endpoint of this study will be the proportion of patients who experience CNS toxicity, with secondary endpoints progression-free survival, overall survival, steroid dosage, development of radionecrosis, quality of life, objective radiographic response and performance status.
- Conditions
- Malignant Glioma
- Being tested
- Stereotactic Radiosurgery (SRS), Bevacizumab
- Keywords
- Recurrent
- Medical subject headings
- Glioma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic Radiosurgery (SRS)Radiation
Tumor Volume < 2.0cm receives 24 Gy in 1 fraction Tumor Volume 2.0-2.9cm receives 18 Gy in 1 faction Tumor Volume 3.0-4.9cm receives 25 Gy in 5Gy/fraction
BevacizumabDrug
Also called Avastin
Bevacizumab (Avastin) 10 mg/kg given the day before SRS and 2 weeks after SRS
| Study group | Role | What they receive |
|---|---|---|
| Stereotactic Radiosurgery | Experimental | Avastin and Radiosurgery Receives: Radiation: Stereotactic Radiosurgery (SRS); Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Central Nervous System (CNS) Toxicity
Number of participants who experience Grade 3 or higher adverse events in the "Nervous System Disorder" domain of Common Toxicity Criteria for Adverse Events (CTCAE) v4.0.
Measured: 2 months after Stereotactic Radiosurgery
Secondary outcomes (16)
Progression-free Survival (PFS)
Time in months from the start of stereotactic radiosurgery (SRS) to the date of first progression according to Revised Assessment in Neuro-Oncology (RANO)criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve. Per RANO, progression is defined as a 20% increase in the sum of the longest diameter of target lesions,or a measurable increase in a non-target lesion or the appearance of new lesions.
Measured: 1 year
Radiographic Response at Month 2
Radiographic response at 2 months after stereotactic radiosurgery (SRS) assessed by MRI and based on modified Response Assessment in Neuro-Oncology (RANO) criteria.Per RANO, complete response (CR) is the disappearance of all target lesions;Partial Response(PR)is a >=30% decrease in the sum of the longest diameter of target lesions.
Measured: 2 months after SRS
Overall Survival(OS)
Time in months from the start of stereotactic radiosurgery (SRS) to date of death due to any cause. Patients alive as of the last follow-up had OS censored at the last follow-up date. Median OS was estimated using a Kaplan-Meier curve.
Measured: 2 years
Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS)
Quality of life as measured by the change in Functional Assessment of Cancer Therapy-Brain (FACT-Br) scores from baseline to 2 months after SRS. The FACT-Br (version 4) is comprised of the Functional Assessment of Cancer Therapy-General (FACT-G), a 27-item core questionnaire evaluating the domains of physical, family/social, emotional and functional well-being, with the addition of 23 brain cancer specific questions. The FACT-G total score is the sum of the four FACT-G domain scores. The Brain Cancer Subscale (BrCS) is the sum of 19 brain cancer specific questions. The FACT-Br Trial Outcome Index (TOI) is the sum of the BrCS score and the physical and family/social domain scores. The FACT-Br total score is the sum of the FACT-G total score and the BrCS score. Higher scores for all scales indicate improved quality of life (QOL).Change score = score at 2 months after SRS - score at baseline. Positive change scores indicate improved quality of life.
Measured: 2 months after SRS
Cognition at 2 Months After Stereotactic Radiosurgery (SRS)as Measured by the Mini-Mental State Exam ( MMSE)
Cognition as measured by the change in the Mini-Mental State Exam (MMSE) scores from baseline to 2 months after SRS. The MMSE is an 11-item measure that tests five areas of cognitive function: orientation, registration, attention and calculation, recall and language. The maximum score is 30. Change score = score at 2 months after SRS - score at baseline. Higher scores for this scale indicate improved quality of life(QOL). Positive change scores indicate improved cognition.
Measured: 2 months after SRS
Cognition at 2 Months After Stereotactic Radiosurgery (SRS) as Measured by the Trail Making Test (TMT)
Cognition as measured by the change in scores on the Trail Making Test (TMT). The TMT consists of two parts. Part A (TMT-A) requires an individual to draw lines sequentially connecting 25 encircled numbers distributed on a sheet of paper. Task requirements are similar for Part B (TMT-B) except the person must alternate between numbers and letters (e.g., 1, A, 2, B, 3, C, etc.). The score on each part represents the amount of time required to complete the task. Shorter time scores indicates improved cognition. Change score = score at 2 months after SRS - score at baseline. Negative change scores indicate improved cognition.
Measured: 2 months after SRS
Performance Status at 2 Months After Stereotactic Radiosurgery (SRS)
Number of patients with a 10% decline in Karnofsky Performance Status (KPS) from baseline to 2 months after SRS. KPS is rated on a 0 to 100 scale representing a patient's ability to perform normal activity, ability to do active work, and the need for assistance. A score of 100 is "perfect" health and 0 represents death.
Measured: 2 months after SRS
Steroid Usage After Stereotactic Radiosurgery (SRS)
Number of patients using steroids at baseline and at 2 months after SRS.
Measured: 2 months after SRS 2 months after SRS 2 months after SRS
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): K-trans
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. K-trans is the widely accepted MR method for quantitating brain tumor microvascular permeability( a measure of blood transport.) K-trans will indicate a combination of both flow and permeability properties of tissue. K-trans will indicate the tissue perfusion per unit volume, with a reduction in K-trans suggesting an increased anti-tumor effect and potentially improved outcome. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Measured: 1 week after SRS
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): K-trans
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. K-trans is the widely accepted MR method for quantitating brain tumor microvascular permeability( a measure of blood transport.) K-trans will indicate a combination of both flow and permeability properties of tissue. K-trans will indicate the tissue perfusion per unit volume with a reduction in K-trans suggesting an increased anti-tumor effect and potentially improved outcome. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Measured: 2 months after SRS
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): AUC
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Area under the curve (AUC) is utilized to measure the signal enhancement ratio washout volume and could be predictive of cancer treatment response. It is possible AUC could be used as a prognostic indicator of the eventual response. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Measured: 1 week after SRS
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): AUC
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Area under the curve (AUC) is utilized to measure the signal enhancement ratio washout volume and could be predictive of cancer treatment response. It is possible AUC could be used as a prognostic indicator of the eventual response. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Measured: 2 months after SRS
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): EVF
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. By measuring extracellular extravascular volume fraction (EVF) it is possible to gain information on brain tissue perfusion. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Measured: 1 week after SRS
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): EVF
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Measured: 2 months after SRS
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): ADC
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Diffusion-weighted imaging, dependent on motion of water molecules, provides information regarding tissue integrity. Apparent diffusion coefficient (ADC) values in the normal brain parenchyma, and those in brain tumors were measured. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Measured: 1 week after SRS
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): ADC
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Diffusion-weighted imaging, dependent on motion of water molecules, provides information regarding tissue integrity. Apparent diffusion coefficient (ADC) values in the normal brain parenchyma, and those in brain tumors were measured. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Measured: 2 months after SRS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2009 (estimated)
- Study startDec 2009
- Primary completionMar 2011
- Study completionFeb 2012
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 Malignant GliomaStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- John Kirkpatrick, MD, PhD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01017250
- Sponsor's protocol ID
- Pro00018943
- Status last verified
- Jan 2014
- First submitted
- 19 Nov 2009
- Last updated
- 28 Feb 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Radiosurgery and Avastin for Recurrent Malignant Gliomas
- ClinicalTrials.gov ID
- NCT01017250
- Acronym / sponsor ID
- Pro00018943
- Conditions
- Malignant Glioma
- Keywords
- Recurrent
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Dec 2009
- Primary completion
- Mar 2011 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 20 Nov 2009 (estimated)
- Results
- Posted 9 May 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the central nervous system (CNS) toxicity in patients with recurrent malignant gliomas treated with concurrent Avastin and stereotactic radiosurgery (SRS).
Detailed description
In this pilot study, 15 human subjects with recurrent, unifocal malignant gliomas up to 5-cm in maximum dimension no longer responding to conventional chemotherapy but able to tolerate further chemotherapy will be enrolled. The primary endpoint of this study will be the proportion of patients who experience CNS toxicity, with secondary endpoints progression-free survival, overall survival, steroid dosage, development of radionecrosis, quality of life, objective radiographic response and performance status.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Stereotactic Radiosurgery | Experimental | Radiation: Stereotactic Radiosurgery (SRS), Drug: BevacizumabAvastin and Radiosurgery |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- History of malignant glioma (WHO Grade III or IV) of the brain treated with some combination of surgery, biochemotherapy and conventionally fractionated external beam radiotherapy
- Radiotherapy completed at least 6 months prior to recurrence
- Age 18 years and older
- New or enlarging contrast-enhancing and/or 18FDG-avid nodule, at least 1 cm diameter
- Estimated life expectancy of 3 months or longer
Key exclusion criteria (13 listed)
- Avastin therapy within 21 days of start of participation
- Contraindication to Avastin therapy or brain MRI
- Presence of bleeding diathesis or coagulopathy
- History of prior arterial thrombotic event, myocardial infarction, angina, CVA, TIA, CABG angioplasty or stenting within 6 months.
- Inadequately controlled hypertension (defined as systolic blood pressure
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 |
|---|---|---|
| Stereotactic Radiosurgery (SRS)Tumor Volume < 2.0cm receives 24 Gy in 1 fraction Tumor Volume 2.0-2.9cm receives 18 Gy in 1 faction Tumor Volume 3.0-4.9cm receives 25 Gy in 5Gy/fraction | Radiation | Stereotactic Radiosurgery |
| BevacizumabAlso: AvastinBevacizumab (Avastin) 10 mg/kg given the day before SRS and 2 weeks after SRS | Drug | Stereotactic Radiosurgery |
Primary outcome
Central Nervous System (CNS) Toxicity
Time frame: 2 months after Stereotactic Radiosurgery
Number of participants who experience Grade 3 or higher adverse events in the "Nervous System Disorder" domain of Common Toxicity Criteria for Adverse Events (CTCAE) v4.0.
16 secondary outcomes
Progression-free Survival (PFS)
Time frame: 1 year
Radiographic Response at Month 2
Time frame: 2 months after SRS
Overall Survival(OS)
Time frame: 2 years
Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS)
Time frame: 2 months after SRS
Cognition at 2 Months After Stereotactic Radiosurgery (SRS)as Measured by the Mini-Mental State Exam ( MMSE)
Time frame: 2 months after SRS
Cognition at 2 Months After Stereotactic Radiosurgery (SRS) as Measured by the Trail Making Test (TMT)
Time frame: 2 months after SRS
Performance Status at 2 Months After Stereotactic Radiosurgery (SRS)
Time frame: 2 months after SRS
Steroid Usage After Stereotactic Radiosurgery (SRS)
Time frame: 2 months after SRS 2 months after SRS 2 months after SRS
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): K-trans
Time frame: 1 week after SRS
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): K-trans
Time frame: 2 months after SRS
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): AUC
Time frame: 1 week after SRS
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): AUC
Time frame: 2 months after SRS
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): EVF
Time frame: 1 week after SRS
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): EVF
Time frame: 2 months after SRS
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): ADC
Time frame: 1 week after SRS
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): ADC
Time frame: 2 months after SRS
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
John Kirkpatrick, MD, PhD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Stereotactic Radiosurgery (SRS) and Bevacizumab in people with Malignant Glioma, run by Duke University 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 5 inclusion and 13 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 28 Feb 2014. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 May 2012). 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?
Central Nervous System (CNS) Toxicity (time frame: 2 months after Stereotactic Radiosurgery). 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 28 Feb 2014.