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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by University of Colorado, Denver
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01201850
First received: September 13, 2010
Last updated: March 5, 2013
Last verified: February 2013
  Purpose

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.

Condition Intervention
Radiation Necrosis
Drug: Bevacizumab (Avastin®)

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Role of Bevacizumab in the Treatment of Radiation Necrosis in Children With Central Nervous System Tumors

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Feasibility of treating pediatric patients with CNS radiation necrosis with bevacizumab [ Time Frame: 13 weeks ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Collect multiple aspects of the patient's clinical status and radiologic imaging [ Time Frame: 13 weeks ] [ Designated as safety issue: Yes ]

    Outcome 1: We will monitor overall neurologic status and symptoms before, during and 1 month following treatment with bevacizumab.

    Outcome 2: The dose and duration of corticosteroid use prior to, during, and up to 1 month following bevacizumab treatment will also be collected and evaluated.

    Outcome 3: We will also follow changes in neuro-imaging through MRI which will include Mass Resonance Spectroscopy (MRS).

    Outcome 4: We will evaluate quality of life using a comprehensive multi-attribute health status classification system developed by a group at McMasters University.



Estimated Enrollment: 10
Study Start Date: July 2010
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
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. An MRI will be done after the first cycle (3 doses/ 6weeks) and then again at the end of therapy.

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).

  Eligibility

Ages Eligible for Study:   1 Year to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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)
  • 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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01201850

Contacts
Contact: Margaret Macy, M.D. 720-777-8856 Margaret.Macy@Childrenscolorado.org
Contact: Debra Schissel, R.N. 720.777.2879 Debra.Schissel@Childrenscolorado.org

Locations
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Margaret Macy, M.D.    720-777-8856    Margaret.Macy@Childrenscolorado.org   
Contact: Debra Schissel, R.N.    720.777.2879    Debra.Schisssel@Chihldrenscolorado.org   
Principal Investigator: Margaret Macy, MD         
Sponsors and Collaborators
University of Colorado, Denver
Genentech, Inc.
Investigators
Principal Investigator: Margaret Macy, MD Children's Hospital Colorado
  More Information

No publications provided

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01201850     History of Changes
Other Study ID Numbers: 10-0418
Study First Received: September 13, 2010
Last Updated: March 5, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Colorado, Denver:
radiation necrosis
Bevacizumab (Avastin®)
Central Nervous System Tumors

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Necrosis
Nervous System Neoplasms
Neoplasms
Neoplasms by Site
Nervous System Diseases
Pathologic Processes
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014