Phase 2
N=54
Bevacizumab and Sorafenib in Treating Patients With Recurrent Glioblastoma Multiforme
Brain and Central Nervous System Tumors
Bottom Line
View on ClinicalTrials.gov: NCT00621686 ↗Enrolled (actual)
54
Serious AEs
33.3%
Results posted
Jan 2017
Primary outcome: Primary: 6-month Progression-free Survival — 0.263; 0.171 proportion of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- bevacizumab (Biological); sorafenib tosylate (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Alliance for Clinical Trials in Oncology
- Primary completion
- Oct 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 6-month Progression-free Survival |
0.263; 0.171 | — |
| SECONDARY Time to Progression |
3.61; 2.66 | 0.069 |
| SECONDARY Overall Survival |
5.58; 5.62 | — |
Summary
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab and sorafenib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving bevacizumab together with sorafenib may kill more tumor cells.
PURPOSE: This phase II trial is studying the side effects and how well giving bevacizumab together with sorafenib works in treating patients with recurrent glioblastoma multiforme.
Eligibility Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed glioblastoma multiforme as determined by pre-registration central pathology review
- Gliosarcoma allowed
- Must have evidence of tumor progression by MRI or CT scan following radiotherapy or the most recent anti-tumor therapy
- No more than 1 chemotherapy regimen for progressive or recurrent disease
- Bidimensionally measurable or evaluable disease by MRI or CT scan
- No evidence of CNS hemorrhage on baseline CT or MRI
- Patients with T1 hyperintensity confined to the surgical cavity which is felt likely due to post surgical blood contaminating the intracavity cerebrospinal fluid or irrigation that have not yet absorbed and which is not felt to clinically or radiographically represent new spontaneous hemorrhage are eligible
- Patients with old blood products or hemosiderin without a history of spontaneous bleeding are eligible
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin > 9.0 g/dL
- Total bilirubin ≤ 1.5 times upper limit of normal
- AST ≤ 3 times upper limit of normal
- Creatinine ≤ upper limit of normal
- Urine protein: creatinine ratio 150 mm Hg or diastolic BP > 100 mm Hg while on antihypertensive medications)
- Patients with well-controlled hypertension are eligible
- No myocardial infarction or unstable angina within the past 6 months
- No congestive heart failure requiring the use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
- No New York Heart Association class II-IV congestive heart failure
- No significant vascular disease (e.g., aortic aneurysm or aortic dissection)
- No peripheral arterial thrombosis within the past 6 months
- No stroke or transient ischemic attack within the past 6 months
- No history of hypertensive crisis or hypertensive encephalopathy
- No evidence of bleeding diathesis (greater than normal risk of bleeding) or coagulopathy (in the absence of therapeutic anticoagulation)
- No active or recent history of hemoptysis (i.e., ≥ ½ teaspoon of bright red blood per episode) within the past 30 days
- No serious, nonhealing wounds, ulcers, or bone fractures
- No condition that impairs the ability to swallow pills (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation)
- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
- No significant traumatic injury within the past 28 days
- No known hypersensitivity to any of the components of sorafenib or bevacizumab
- No other active malignancy within the past 3 years, except nonmelanoma skin cancer or carcinoma in situ of the cervix
- Patients with a history of prior malignancy must not be receiving specific treatment (other than hormonal therapy) for that malignancy
- No co-morbid systemic illness or other concurrent severe disease that, in the judgment of the investigator, would make the patient inappropriate for entry into this study or significantly interfere with the proper assessment of safety and toxicity of the prescribed study regimen
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- At least 12 weeks since prior radiotherapy
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
- More than 2 weeks since prior small molecule cell cycle inhibitors
- At least 1 week since prior fixed-dose corticosteroids (or no corticosteroids)
- No prior intratumoral chemotherapy, stereotactic radiosurgery or interstitial brachytherapy unless there is a separate lesion on MRI that is not part of the prior treatment field OR there is proof of recurrent disease based on biopsy, MRI spectroscopy, or PET scan
- No prior antiangiogenic therapy
- No prior surgical procedures affecting absorption
- More than 7 days since prior core biopsy or other minor surgical procedures
- Placement of a vascular access device is allowed
- More than 28 days since prior major surgical p
Data sourced from ClinicalTrials.gov (NCT00621686). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.