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The Role of Bevacizumab in the Treatment of Radiation Necrosis in Children With Central Nervous System Tumors

1 Year
25 Years
Open (Enrolling)
Radiation Necrosis

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Trial Information

The Role of Bevacizumab in the Treatment of Radiation Necrosis in Children With Central Nervous System Tumors

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).

Inclusion Criteria:

- 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

- 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)

- 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) institutional upper limit of normal (ULN) for age;

- Adequate Renal Function defined as:

- Serum creatinine 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
- Alanine Amniotransferase (ALT) and Aspartate Aminotransferase(AST) ULN for institution;Serum albumin
- 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

- 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

Exclusion Criteria:

1. 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.

2. 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

- 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.

3. 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Feasibility of treating pediatric patients with CNS radiation necrosis with bevacizumab

Outcome Description:

This pilot study is designed to evaluate the feasibility of treating pediatric patients with CNS radiation necrosis with bevacizumab. This regimen will be deemed feasible if a majority (7 out of 10) patients are able to successfully receive at least 5 of the 6 scheduled doses of bevacizumab without increase in serious adverse events as compared to patients post-radiation therapy alone.

Outcome Time Frame:

13 weeks

Safety Issue:


Principal Investigator

Margaret Macy, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Hospital Colorado


United States: Institutional Review Board

Study ID:




Start Date:

July 2010

Completion Date:

February 2015

Related Keywords:

  • Radiation Necrosis
  • radiation necrosis
  • Bevacizumab (Avastin®)
  • Central Nervous System Tumors
  • Necrosis
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms



Children's Hospital ColoradoAurora, Colorado  80045