Clinical Trial 19433

Cancer Type:
Interventions:Avastin (Bevacizumab); Bevacizumab; Dexamethasone; Placebo; prednisone

Study Type: Treatment
Phase of Study: Phase II

  • Sepideh Mokhtari


Study Title

Randomized Phase II Study: Corticosteroids + Bevacizumab vs. Corticosteroids + Placebo (BeSt) for Radionecrosis after Radiosurgery for Brain Metastases


The purpose of this study is test whether adding a drug called bevacizumab to standard corticosteroid therapy will improve the participant's symptoms over corticosteroid therapy alone by improving the radionecrosis and minimizing treatment-related side effects. The effects of bevacizumab with standard corticosteroid therapy will be compared to a placebo with standard corticosteroid therapy.


2.0 OBJECTIVES 2.1 Primary Objective: To investigate whether the addition of bevacizumab to standard corticosteroid therapy results in greater improvement in symptoms (clinical and patient-reported symptom improvement associated with radionecrosis and less radionecrosis treatment-induced symptoms) compared with standard corticosteroid therapy. 2.2 Secondary Objectives: 2.2.1 To evaluate the toxicity profile associated with bevacizumab and corticosteroid therapy. 2.2.2 To compare self-reported health related quality of life (HRQOL) using LASA, Dexamethasone Symptoms Questionnaire-Chronic (DSQ-C), and MDASI-BT symptom and interference score between treatment arms. 2.2.3 To compare intracranial progression-free survival and time to maximum radiographic response between treatment arms. 2.2.4 To compare the dose and duration of corticosteroids required between treatment arms and correlate steroid requirement with DSQ-C and MDASI-BT scores. 2.3 Correlative Objectives: 2.3.1 To explore serum/urine biomarkers that predict for treatment response. 2.3.2 To explore early imaging biomarkers that predict for treatment response.

Inclusion Criteria

  • Patients who present with symptomatic brain radionecrosis after they have received radiosurgery for brain metastases from primary solid tumor including but not limited to lung, breast, colorectal cancer but excluding melanoma, choriocarcinoma, renal cell carcinoma or gliomas.
  • Patients at institutions that elect to utilize central imaging review to confirm eligibility must be pre-registered prior to submission of these images; images should be submitted as soon as possible after the pre-registration magnetic resonance imaging (MRI) is obtained; turnaround time for this review will be ≤ 72 business hours after receipt of images by the Imaging and Radiation Oncology Core (IROC).
  • Patients at institutions that elect to confirm eligibility locally may be pre-registered at the same time as they are randomized.
  • A diagnosis of radionecrosis will be based on a clinical onset of symptoms and radiological findings of radionecrosis at 3-24 months following radiosurgery, with or without pathological confirmation
  • Must have been taking a stable dose of corticosteroids for symptom management for at least 1 week before baseline MRI.
  • No systemic therapy within 2 weeks prior to registration or plan for systemic therapy within the first 8 weeks after study registration. The protocol provides a list of 'approved systemic' therapies that are allowed for concurrent use with bevacizumab.
  • No bevacizumab ≤ 3 months of study registration.
  • Central imaging real-time review (72 hour turn around) to confirm eligibility.
  • Not pregnant and not nursing. For women of childbearing potential only, a negative urine or serum pregnancy test done ≤ 14 days prior to registration and confirmation they are not nursing is required.
  • Age ≥ 18 years
  • Karnofsky Performance Status ≥ 60%.
  • Required Initial Laboratory Values ≤14 days of registration.
  • Able to participate in patient-report outcomes (MDASI-BT, DSQ-C, LASA) questionnaires. Assistance by research personnel is acceptable if participant has disabilities that make reading or writing difficult.

  • Exclusion Criteria

  • Evidence of recent hemorrhage at pre-registration MRI of the brain, however the following are permitted: presence of hemosiderin, resolving hemorrhagic changes related to surgery, and presence of punctate hemorrhage in the tumor.
  • Excess risk of bleeding (any of the following): Bleeding diathesis or coagulopathy; Thrombocytopenia; Major surgical procedure, open biopsy, or significant traumatic injury within the past 28 days or anticipation of need for major surgical procedure during the course of the study; Minor surgical procedures, stereotactic biopsy, fine needle aspiration, or core biopsy within the past 7 days.
  • Clinically significant cardiovascular disease.
  • History of bowel obstruction, abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within past 12 months.
  • Central lung metastases with excessive active bleeding.
  • Uncontrolled intercurrent illness including, but not limited to any of the following: ongoing or active infection requiring IV antibiotics, cardiac arrhythmia, or psychiatric illness and/or social situations that would limit compliance with study requirements.
  • History of serious non-healing wound, ulcer, or bone fractures.