Radiation NecrosisNCT01201850
The Role of Bevacizumab in the Treatment of Radiation Necrosis in Children With Central Nervous System Tumors
A study testing Bevacizumab (Avastin®) in people with Radiation Necrosis, run by University of Colorado, Denver at 1 site in United States.
Trial summary
This study is being done to learn about the safety of the study drug bevacizumab(Avastin®), when used to treat radiation necrosis. The primary objective of this study is to test the feasibility of treating Central Nervous System (CNS) tumor patients suffering from radiation necrosis with bevacizumab every 2 weeks. Read more about this study
- Who is it for?
- Ages 1 year to 25 years
- Conditions the study is for
- Radiation Necrosis
- What is being tested?
- Bevacizumab (Avastin®)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Jun 2010to 4 Aug 2016
- 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 1 year to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age ≥ 1 and < 25 years of age at diagnosis
- Interval from radiation therapy at least 4 weeks and no more than 1 year
- Neurologic deterioration (long tract signs, cranial nerve signs or ataxia) consistent with radiation necrosis
- MRI imaging with findings consistent with radiation necrosis as confirmed by the study radiologist
- Craniotomy or intracranial biopsy site must be adequately healed, free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of study entry
- More than 28 days elapsed from the last surgical procedure (including biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity)
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- Lansky or Karnofsky performance > 40%
- Patients may be on steroids at study entry
- Adequate organ function defined as:
- Peripheral absolute neutrophil (ANC) >/= 1000/units/Liter(uL)
- Platelet count >/= 50,000/uL
- Hemoglobin >/= 9.0 gm/dL (transfusion permitted)
- Adequate Coagulation function defined as:
- Prothrombin Time (PT)/activated Partial Thromboplastin Time (aPTT) </= 1.5x institutional upper limit of normal (ULN) for age;
- Adequate Renal Function defined as:
- Serum creatinine </= 1.5x institutional upper limit of normal (ULN) for age. If the serum creatinine is above these values, the calculated creatinine clearance or radioisotope Glomerular Filtration Rate (GFR) must be >/= 60 mL/min/1.73m2;
- Adequate Hepatic Function defined as:
- Total bilirubin </= 1.5x institutional upper limit of normal (ULN);
- Alanine Amniotransferase (ALT) and Aspartate Aminotransferase(AST) </= 2.5x ULN for institution;Serum albumin </= 2.0 g/dL;
- QT corrected (QTc) interval within normal range for age;
- Adequate Pulmonary Function defined as:
- Room air oxygen saturation of >90% at altitude > 5000 feet, or >93% < 5000 feet
- Chemotherapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy prior to entering study. Three (3) weeks must have elapsed since the administration of prior chemotherapy.
- Biologic agents: At least 14 days must have elapsed since the completion of therapy with a monoclonal antibody
- Stem cell transplant: patients who have undergone prior stem cell transplant will not be excluded from study entry as long as adequate marrow reserve is demonstrated (refer to hematologic parameters).
- For females of childbearing potential, a negative serum pregnancy test must be documented prior to enrollment
- Patients who enter this study and their sexual partners who are of childbearing potential must agree to use an effective form of contraception throughout participation in this study
- Written informed consent and assent as required by institutional guidelines
Who cannot join
- Disease-Specific Exclusions
- •Evidence of recent (less than 2 weeks) hemorrhage on postoperative MRI of the brain. However, patients with clinically asymptomatic presence of hemosiderin, resolving hemorrhagic changes related to surgery, and presence of punctate hemorrhage in the tumour are permitted entry into the study.
- General Medical Exclusions
- Subjects meeting any of the following criteria are ineligible for study entry:
- Inability to comply with study and/or follow-up procedures
- Life expectancy of less than 12 weeks
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- Patients who have had chemotherapy within three (3) weeks or radiation within four (4) weeks. Patients may not receive additional chemotherapeutic agents while on this study.
- Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
- Active second malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within last five years.
- Bevacizumab-Specific Exclusions
- Inadequately controlled hypertension (defined as above the normal published range for age and height)
- Prior history of hypertensive crisis or hypertensive encephalopathy
- New York Heart Association (NYHA) Grade II or greater congestive heart failure
- History of myocardial infarction or unstable angina within 12 months prior to Day 1
- No history of stroke or transient ischemic attack
- Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1; History of hemoptysis (greater than or equal to 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
- Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
- History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
- Serious, non-healing wound, active ulcer, or unhealed bone fracture
- Proteinuria as demonstrated by a Urine Protein Creatinine (UPC) ratio greater than or equal to 1.0 at screening
- Known hypersensitivity to any component of bevacizumab
- Pregnancy (positive pregnancy test) or lactation. Use of effective means of contraception (men and women) in subjects of child-bearing potential
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital Colorado
Aurora, Colorado, 80045
About this study
This study is being done to learn about the safety of the study drug bevacizumab(Avastin®), when used to treat radiation necrosis.
The primary objective of this study is to test the feasibility of treating Central Nervous System (CNS) tumor patients suffering from radiation necrosis with bevacizumab every 2 weeks.
Read more
The secondary objectives of this study are:
- To evaluate improvement in neurologic symptoms associated with bevacizumab as assessed by clinical evaluation;
- To investigate the neuro-imaging changes in radiation necrosis associated edema, including Mass Resonance (MR) spectroscopy;
- To evaluate changes in corticosteroid use in patients with radiation necrosis following treatment with bevacizumab;
- To evaluate changes in quality of life.
Read the detailed description
Treatment Plan:
For patient consented and enrolled on study, bevacizumab will be administered at a dose of 10 mg/kg IV every 2 weeks for a total of 6 doses (3 doses/cycle).
Patients are expected to receive at least 1 cycle (6 weeks) of study treatment unless an unacceptable drug reaction occurs. Patients will receive a second cycle of treatment as long as treatment is tolerated. Response assessment will be performed every 6 weeks (three doses/cycle of study drug) including clinical and radiological assessment. Secondary measures including documentation of total equivalent steroid dose, length of time on steroids, and quality of life using the modified McMaster Health Instrument scale will also be collected while on treatment and 30 days after finishing treatment.
Safety will be assessed by routine physical and laboratory evaluations. Adverse events will be recorded and the severity graded according to the NCI Common Terminology Criteria for Adverse Events (version 4.0).
- Conditions
- Radiation Necrosis
- Being tested
- Bevacizumab (Avastin®)
- Keywords
- radiation necrosis, Bevacizumab (Avastin®), Central Nervous System Tumors
- Medical subject headings
- Central Nervous System Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bevacizumab (Avastin®)Drug
Once enrolled on study, patients will be treated with bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses. An MRI will be done after the first cycle (3 doses/ 6weeks) and then again at the end of therapy.
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab (Avastin®) | Experimental | Once enrolled on study, patients will be treated with bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses. Receives: Drug: Bevacizumab (Avastin®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Received at Least 5 of the 6 Scheduled Doses of Bevacizumab
This pilot study was designed to evaluate the feasibility of treating pediatric patients with CNS radiation necrosis with bevacizumab. Patients enrolled on study were assessed for number of doses of bevacizumab that they received while on study. Participants who successfully received at least 5 of the 6 planned doses of bevacizumab (IV every 2 weeks) without significant events were determined to have met the outcome measure.
Measured: 13 weeks
Secondary outcomes (4)
Neurologic Status With Bevacizumab Treatment
Outcome 1: Monitor overall neurologic status and symptoms before, during and 1 month following treatment with bevacizumab.
Measured: 13 weeks
Corticosteroid Usage With Bevacixumab Treatment
Outcome 2: Dose and duration of corticosteroid use prior to, during, and up to 1 month following bevacizumab treatment will also be collected and evaluated.
Measured: 13 weeks
Changes in Quality of Life With Bevacizumab Treatment
Outcome 3: To evaluate changes in quality of life before and after treatment with bevacizumab Modified McMasters Scale was used. Minimum score: 1 Maximum score 35. Higher score indicates worse quality of life.
Measured: 13 weeks
Number of Patients With Changes in Neuro-Imaging With Bevacizumab Treatment
Outcome 4: To investigate the neuro-imaging changes in radiation necrosis associated edema, including Mass Resonance (MR) spectroscopy; MRIs (including FLAIR sequences and contrast enhanced images) were evaluated for changes in the radiation necrosis imaging characteristics by a pediatric radiologist. Decreases in gadolinium enhancement, FLAIR signal were considered changes consistent with decreased edema. Tumor size was also evaluated, with a decrease in tumor size indicating decreased edema/improved radiation necrosis
Measured: 13 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2010 (estimated)
- Study start28 Jun 2010
- Primary completion4 Aug 2016
- Study completion4 Aug 2016
Why it stopped: Poor accrual
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 Radiation NecrosisStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Margaret Macy, MD, Principal investigator, Children's Hospital Colorado
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01201850
- Sponsor's protocol ID
- 10-0418.cc
- Status last verified
- Apr 2021
- First submitted
- 13 Sep 2010
- Last updated
- 19 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Bevacizumab in the Treatment of Radiation Necrosis in Children With Central Nervous System Tumors
- ClinicalTrials.gov ID
- NCT01201850
- Acronym / sponsor ID
- 10-0418.cc
- Conditions
- Radiation Necrosis
- Keywords
- radiation necrosis, Bevacizumab (Avastin®), Central Nervous System Tumors
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor accrual
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- 28 Jun 2010 (actual)
- Primary completion
- 4 Aug 2016 (actual)
- Study completion
- 4 Aug 2016 (actual)
- First posted
- 15 Sep 2010 (estimated)
- Results
- Posted 29 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being done to learn about the safety of the study drug bevacizumab(Avastin®), when used to treat radiation necrosis.
The primary objective of this study is to test the feasibility of treating Central Nervous System (CNS) tumor patients suffering from radiation necrosis with bevacizumab every 2 weeks.
The secondary objectives of this study are:
- To evaluate improvement in neurologic symptoms associated with bevacizumab as assessed by clinical evaluation;
- To investigate the neuro-imaging changes in radiation necrosis associated edema, including Mass Resonance (MR) spectroscopy;
- To evaluate changes in corticosteroid use in patients with radiation necrosis following treatment with bevacizumab;
- To evaluate changes in quality of life.
Detailed description
Treatment Plan:
For patient consented and enrolled on study, bevacizumab will be administered at a dose of 10 mg/kg IV every 2 weeks for a total of 6 doses (3 doses/cycle).
Patients are expected to receive at least 1 cycle (6 weeks) of study treatment unless an unacceptable drug reaction occurs. Patients will receive a second cycle of treatment as long as treatment is tolerated. Response assessment will be performed every 6 weeks (three doses/cycle of study drug) including clinical and radiological assessment. Secondary measures including documentation of total equivalent steroid dose, length of time on steroids, and quality of life using the modified McMaster Health Instrument scale will also be collected while on treatment and 30 days after finishing treatment.
Safety will be assessed by routine physical and laboratory evaluations. Adverse events will be recorded and the severity graded according to the NCI Common Terminology Criteria for Adverse Events (version 4.0).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab (Avastin®) | Experimental | Drug: Bevacizumab (Avastin®)Once enrolled on study, patients will be treated with bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses. |
Who may qualify
- Ages
- 1 year to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (28 listed)
- Age ≥ 1 and < 25 years of age at diagnosis
- Interval from radiation therapy at least 4 weeks and no more than 1 year
- Neurologic deterioration (long tract signs, cranial nerve signs or ataxia) consistent with radiation necrosis
- MRI imaging with findings consistent with radiation necrosis as confirmed by the study radiologist
- Craniotomy or intracranial biopsy site must be adequately healed, free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of study entry
Key exclusion criteria (24 listed)
- Disease-Specific Exclusions
- •Evidence of recent (less than 2 weeks) hemorrhage on postoperative MRI of the brain. However, patients with clinically asymptomatic presence of hemosiderin, resolving hemorrhagic changes related to surgery, and presence of punctate hemorrhage in the tumour are permitted entry into the study.
- General Medical Exclusions
- Bevacizumab-Specific Exclusions
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 |
|---|---|---|
| Bevacizumab (Avastin®)Once enrolled on study, patients will be treated with bevacizumab (10mg/kg) intravenously (i.v.) every 2 weeks for a total of 6 doses. An MRI will be done after the first cycle (3 doses/ 6weeks) and then again at the end of therapy. | Drug | Bevacizumab (Avastin®) |
Primary outcome
Number of Participants Who Received at Least 5 of the 6 Scheduled Doses of Bevacizumab
Time frame: 13 weeks
This pilot study was designed to evaluate the feasibility of treating pediatric patients with CNS radiation necrosis with bevacizumab. Patients enrolled on study were assessed for number of doses of bevacizumab that they received while on study. Participants who successfully received at least 5 of the 6 planned doses of bevacizumab (IV every 2 weeks) without significant events were determined to have met the outcome measure.
4 secondary outcomes
Neurologic Status With Bevacizumab Treatment
Time frame: 13 weeks
Corticosteroid Usage With Bevacixumab Treatment
Time frame: 13 weeks
Changes in Quality of Life With Bevacizumab Treatment
Time frame: 13 weeks
Number of Patients With Changes in Neuro-Imaging With Bevacizumab Treatment
Time frame: 13 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2021.
- 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.
Margaret Macy, MD principal investigator
Children's Hospital Colorado
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Bevacizumab (Avastin®) in people with Radiation Necrosis, run by University of Colorado, Denver 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 28 inclusion and 24 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 19 May 2021. 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 29 Apr 2021). 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 Who Received at Least 5 of the 6 Scheduled Doses of Bevacizumab (time frame: 13 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 19 May 2021.