Dasatinib and Bevacizumab in Treating Patients With Recurrent or Progressive High-Grade Glioma or Glioblastoma Multiforme
Glioblastoma Multiforme
About this trial
This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring adult giant cell glioblastoma, adult glioblastoma, adult gliosarcoma, adult mixed glioma, recurrent adult brain tumor, adult anaplastic oligodendroglioma, adult oligodendroglioma, adult anaplastic astrocytoma
Eligibility Criteria
Patient Eligibility:
I. Pre-registration:
1. Central pathology review submission. This review is mandatory prior to registration to confirm eligibility.
II. Registration Inclusion Criteria:
- ≥18 years of age
- Study 1: Histologic confirmation of grade 3 or 4 glioma, including astrocytoma, oligodendroglioma, and mixed gliomas, as determined by pre-registration central pathology review.
- Study 2: Histological confirmation of glioblastoma multiforme (grade 4 astrocytoma) as determined by pre-registration central pathology review. NOTE: Variant gliosarcomas are eligible
- Evidence of tumor progression by MRI or CT scan following RT or following the most recent anti-tumor therapy. Patients who had surgical treatment at recurrence are eligible if there is imaging evidence of disease progression as compared to the first postoperative scan.
- Bidimensionally measurable or evaluable disease by MRI or CT scan.
- ECOG Performance Status (PS) 0, 1, or 2.
- Patient willing to discontinue use of aspirin or medications that inhibit platelet function ≥ 1 week prior to registration.
- Previous RT and ≥12 weeks since the completion of RT prior to registration.
The following laboratory values obtained ≤ 21 days prior to registration.
- ANC ≥1500
- PLT ≥100,000
- Hgb >9.0 g/dL
- T. bili ≤1.5 x ULN
- SGOT (AST) ≤ 3 x ULN
- Creatinine ≤ ULN
- UPC ratio <1. NOTE: Urine protein must be screened by urine analysis for Urine Protein Creatinine (UPC) ratio. For UPC ratio ≥1.0, 24-hour urine protein must be obtained and the level should be <1000 mg
- Negative pregnancy test done ≤7 days prior to registration, for women of childbearing potential only.
- Ability to complete questionnaire(s) by themselves or with assistance.
- Provide informed written consent
- Willingness to return to enrolling institution for follow-up.
- Patient willing to provide mandatory tissue samples for research purposes
- Study 1: Any number of prior chemotherapy regimens for recurrent disease. Study 2: Up to 2 prior chemotherapy regimens with ≤1 regimen for recurrent disease.
III. Exclusion Criteria:
- Pregnant women, nursing women and men or women of childbearing potential who are unwilling to employ adequate contraception during this study and for up to 6 months after bevacizumab treatment has ended. NOTE: bevacizumab and dasatinib are investigational agents whose genotoxic effects on the developing fetus and newborn are unknown.
Prior intratumoral therapy, stereotactic radiosurgery, or interstitial brachytherapy.
EXCEPTION: Separate lesion on MRI which is not part of the previous treatment field, or convincing evidence of recurrent disease, based on biopsy, MRI spectroscopy, or PET scan.
- Prior treatment with bevacizumab or VEGF-Trap (Aflibercept).
Inadequately controlled hypertension (systolic blood pressure of >150 mmHg or diastolic pressure >100 mmHg on anti-hypertensive medications).
NOTE: Patients with well-controlled hypertension are eligible.
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
- Immunocompromised patients (other than that related to the use of corticosteroids). NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this study.
- Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, or prior surgical procedures affecting absorption) that impairs ability to swallow pills.
- Receiving therapeutic anticoagulation with Warfarin. NOTE: Prophylactic anticoagulation (i.e., low dose warfarin) of venous or arterial access devices is allowed, provided that INR <1.5. Therapeutic anti-coagulation with low molecular weight heparin is allowed at time of registration.
- Evidence of bleeding diathesis (greater than normal risk of bleeding) or coagulopathy (in the absence of therapeutic anticoagulation).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
- Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
- Other active malignancy ≤3 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer or carcinoma in-situ of the cervix. Note: If there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer.
- History of myocardial infarction or unstable angina ≤6 months prior to registration.
- New York Heart Association (NYHA) classification II, III or IV congestive heart failure.
- Core biopsy or other minor surgical procedures ≤7 days prior to registration. Note: Placement of a vascular access device is allowed.
- Major surgical procedure, open biopsy, or significant traumatic injury ≤28 days prior to registration or anticipation of need for major surgical procedure during the course of the study.
- Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis ≤6 months prior to registration.
- History of hypertensive crisis or hypertensive encephalopathy.
- Known hypersensitivity to any of the components of dasatinib or bevacizumab.
- Serious, non-healing wound, active ulcer, or untreated bone fracture
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess ≤6 months prior to registration.
- Active or recent history of hemoptysis (≥ ½ teaspoon of bright red blood per episode) ≤30 days prior to registration.
- History of stroke or transient ischemic attack (TIA) ≤6 months prior to registration.
- Any evidence of CNS hemorrhage on baseline CT or MRI
Any of the following Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes ≤7 days prior to registration (patients must discontinue drug 7 days prior to starting dasatinib)
- Quinidine, procainamide, disopyramide
- Amiodarone, sotalol, ibutilide, dofetilide
- Erythromycin, clarithromycin
- Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
- Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
- Prochlorperazine
- Diagnosed congenital long QT syndrome
- Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes)
- Prolonged QTc interval on pre-entry electrocardiogram (>450 msec)
Patients may not have any clinically significant cardiovascular disease including the following:
- Myocardial infarction or ventricular tachyarrhythmia within 6 months.
- Prolonged QTc ≥ 480 msec (Fridericia correction)
- Ejection fraction less than institutional normal
- Major conduction abnormality (unless a cardiac pacemaker is present)
Note: Patients with any cardiopulmonary symptoms of unknown cause (e.g., shortness of breath, chest pain, etc.) should be evaluated by a baseline echocardiogram with or without stress test as needed in addition to electrocardiogram (ECG) to rule out QTc prolongation. The patient may be referred to a cardiologist at the discretion of the principal investigator. Patients with underlying cardiopulmonary dysfunction should be excluded from the study.
- Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration
- Known pleural or pericardial effusion of any grade
- Concomitant use of H2 blockers or proton pump inhibitors that cannot be discontinued or switched to locally acting agents (i.e. famotidine or omeprazole.)
- Use of the following Enzyme Inducing Anti-Convulsive (EIAC) medications is prohibited ≤ 7 days prior to registration: carbamazepine (Tegretol®, Tegretol XR®, Carbatrol®), phenytoin (Dilantin®, Phenytek®), fosphenytoin (Cerebyx®), phenobarbital, pentobarbital and primidone (Mysoline®). Note: Many antiepileptic drugs induce hepatic enzymes. Because dasatinib is metabolized by hepatic enzymes, patients taking antiepileptic medications that induce hepatic enzymes (EIACs) are ineligible for this trial. To be eligible for this trial, patients taking EIACs must be switched to non-EIACs ≥ 7 days prior to registration. The following agents are not known to affect dasatinib metabolism and are acceptable for use: valproic acid (Depakote®, Depacon®), gabapentin (Neurontin®), lamotrigine (Lamictal®), topiramate (Topamax®), tiagabine (Gabitril®), zonisamide (Zonegran®), levetiracetam (Keppra®), clonazepam (Klonopin®) and clobazam (Frisium®).
Sites / Locations
- Mayo Clinic Scottsdale
- Rebecca and John Moores UCSD Cancer Center
- Palchak David MD
- Aurora Presbyterian Hospital
- Boulder Community Hospital
- Boulder Community Hospital
- Penrose Cancer Center at Penrose Hospital
- St. Anthony Central Hospital
- Porter Adventist Hospital
- Presbyterian - St. Luke's Medical Center
- St. Joseph Hospital
- Rose Medical Center
- Swedish Medical Center
- North Colorado Medical Center
- Sky Ridge Medical Center
- Hope Cancer Care Center at Longmont United Hospital
- McKee Medical Center
- St. Mary - Corwin Regional Medical Center
- Exempla Lutheran Medical Center
- Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
- Beebe Medical Center
- Tunnell Cancer Center at Beebe Medical Center
- CCOP - Christiana Care Health Services
- Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
- Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
- Memorial Cancer Institute at Memorial Regional Hospital
- Memorial Regional Hospital/Joe DiMaggio Children's Hospital
- Mayo Clinic - Jacksonville
- Ella Milbank Foshay Cancer Center at Jupiter Medical Center
- CCOP - Mount Sinai Medical Center
- Florida Hospital Cancer Institute at Florida Hospital Orlando
- John B Amos Cancer Center
- Kapiolani Medical Center at Pali Momi
- Oncare Hawaii, Incorporated - Pali Momi
- Cancer Research Center of Hawaii
- Oncare Hawaii Inc-POB II
- OnCare Hawaii, Incorporated - Lusitana
- Queen's Cancer Institute at Queen's Medical Center
- Straub Clinic and Hospital, Incorporated
- University of Hawaii
- Kuakini Medical Center
- OnCare Hawaii, Incorporated - Kuakini
- Kapiolani Medical Center for Women and Children
- Castle Medical Center
- Kauai Medical Clinic
- Wilcox Memorial Hospital and Kauai Medical Clinic
- Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
- Rush-Copley Cancer Care Center
- Illinois CancerCare - Bloomington
- Illinois CancerCare - Canton
- Illinois CancerCare - Carthage
- Rush University Medical Center
- Eureka Community Hospital
- Illinois CancerCare - Eureka
- Galesburg Clinic, PC
- Illinois CancerCare - Havana
- Illinois CancerCare - Kewanee Clinic
- Illinois CancerCare - Macomb
- Illinois CancerCare - Monmouth
- BroMenn Regional Medical Center
- Community Cancer Center
- Illinois CancerCare - Community Cancer Center
- Community Hospital of Ottawa
- Illinois CancerCare-Ottawa Clinic
- Oncology Hematology Associates of Central Illinois, PC - Ottawa
- Ottawa Regional Hospital and Healthcare Center
- Cancer Treatment Center at Pekin Hospital
- Illinois CancerCare - Pekin
- Proctor Hospital
- CCOP - Illinois Oncology Research Association
- Oncology Hematology Associates of Central Illinois, PC - Peoria
- Methodist Medical Center of Illinois
- Illinois CancerCare - Peru
- Illinois Valley Community Hospital
- Illinois CancerCare - Princeton
- Illinois CancerCare - Spring Valley
- CCOP - Carle Cancer Center
- St. Francis Hospital Cancer Care Services
- Reid Hospital & Health Care Services
- McFarland Clinic, PC
- Cedar Rapids Oncology Association
- Mercy Hospital
- Oncology Associates at Mercy Medical Center
- Medical Oncology and Hematology Associates - West Des Moines
- Mercy Cancer Center - West Lakes
- CCOP - Iowa Oncology Research Association
- John Stoddard Cancer Center at Iowa Methodist Medical Center
- Medical Oncology and Hematology Associates at John Stoddard Cancer Center
- Medical Oncology and Hematology Associates at Mercy Cancer Center
- Mercy Cancer Center at Mercy Medical Center - Des Moines
- John Stoddard Cancer Center at Iowa Lutheran Hospital
- Mercy Cancer Center at Mercy Medical Center - North Iowa
- Siouxland Hematology-Oncology Associates, LLP
- Mercy Medical Center - Sioux City
- St. Luke's Regional Medical Center
- Methodist West Hospital
- Mercy Medical Center-West Lakes
- Cancer Center of Kansas - Chanute
- Cancer Center of Kansas, PA - Chanute
- Cancer Center of Kansas - Dodge City
- Cancer Center of Kansas, PA - Dodge City
- Cancer Center of Kansas - El Dorado
- Cancer Center of Kansas, PA - El Dorado
- Cancer Center of Kansas - Fort Scott
- Cancer Center of Kansas-Independence
- Cancer Center of Kansas, PA - Kingman
- Lawrence Memorial Hospital
- Cancer Center of Kansas, PA - Liberal
- Cancer Center of Kansas - Newton
- Cancer Center of Kansas, PA - Newton
- Cancer Center of Kansas - Parsons
- Cancer Center of Kansas, PA - Parsons
- Cancer Center of Kansas - Pratt
- Cancer Center of Kansas, PA - Pratt
- Cancer Center of Kansas - Salina
- Cancer Center of Kansas, PA - Salina
- Cancer Center of Kansas - Wellington
- Cancer Center of Kansas, PA - Wellington
- Associates in Women's Health - Wichita
- Associates in Womens Health, PA - North Review
- Cancer Center of Kansas, PA - Medical Arts Tower
- Cancer Center of Kansas - Main Office
- Cancer Center of Kansas, PA - Wichita
- CCOP - Wichita
- Via Christi Cancer Center at Via Christi Regional Medical Center
- Wesley Medical Center
- Cancer Center of Kansas - Winfield
- Cancer Center of Kansas, PA - Winfield
- Harold Alfond Center for Cancer Care
- CancerCare of Maine at Eastern Maine Medical Center
- Union Hospital of Cecil County
- Bixby Medical Center
- Hickman Cancer Center at Bixby Medical Center
- Toledo Clinic Cancer Centers - Adrian
- Toledo Clinic Cancer Centers-Adrian
- Saint Joseph Mercy Cancer Center
- CCOP - Michigan Cancer Research Consortium
- Oakwood Cancer Center at Oakwood Hospital and Medical Center
- Saint John Hospital and Medical Center
- Hurley Medical Center
- Van Elslander Cancer Center at St. John Hospital and Medical Center
- Foote Memorial Hospital
- Sparrow Regional Cancer Center
- St. Mary Mercy Hospital
- Community Cancer Center of Monroe
- Mercy Memorial Hospital - Monroe
- Toledo Clinic Cancer Centers-Monroe
- St. Joseph Mercy Oakland
- Mercy Regional Cancer Center at Mercy Hospital
- Saint Joseph Mercy Port Huron
- Seton Cancer Institute at Saint Mary's - Saginaw
- St. John Macomb Hospital
- MeritCare Bemidji
- Sanford Clinic North-Bemidji
- Fairview Ridges Hospital
- Mercy and Unity Cancer Center at Mercy Hospital
- Essentia Health - Duluth Clinic
- CCOP - Duluth
- Essentia Health Saint Mary's Medical Center
- Miller - Dwan Medical Center
- Fairview Southdale Hospital
- Mercy and Unity Cancer Center at Unity Hospital
- Hutchinson Area Health Care
- HealthEast Cancer Care at St. John's Hospital
- Minnesota Oncology - Maplewood
- Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
- Hennepin County Medical Center - Minneapolis
- New Ulm Medical Center
- Humphrey Cancer Center at North Memorial Outpatient Center
- Mayo Clinic Cancer Center
- CentraCare Clinic - River Campus
- Coborn Cancer Center
- Saint Cloud Hospital
- CCOP - Metro-Minnesota
- Park Nicollet Cancer Center
- Regions Hospital Cancer Care Center
- United Hospital
- St. Francis Cancer Center at St. Francis Medical Center
- Lakeview Hospital
- Ridgeview Medical Center
- Willmar Cancer Center at Rice Memorial Hospital
- Minnesota Oncology - Woodbury
- Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
- Washington University School of Medicine
- CCOP - Montana Cancer Consortium
- St. Vincent Healthcare Cancer Care Services
- Frontier Cancer Center and Blood Institutes-Billings
- Hematology-Oncology Centers of the Northern Rockies - Billings
- Billings Clinic - Downtown
- Billings Clinic
- Bozeman Deaconess Cancer Center
- Bozeman Deaconess Hospital
- St. James Healthcare Cancer Care
- Benefis Healthcare - Sletten Cancer Institute
- Benefis Sletten Cancer Institute
- St. Peter's Hospital
- Kalispell Regional Medical Center
- Montana Cancer Specialists at Montana Cancer Center
- Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
- Saint Francis Cancer Treatment Center at Saint Francis Memorial Health Center
- Cancer Resource Center - Lincoln
- Nebraska Cancer Research Center
- Callahan Cancer Center at Great Plains Regional Medical Center
- CCOP - Missouri Valley Cancer Consortium
- Immanuel Medical Center
- Alegant Health Cancer Center at Bergan Mercy Medical Center
- Alegent Health Lakeside Hospital
- Lakeside Hospital
- Creighton University Medical Center
- UNMC Eppley Cancer Center at the University of Nebraska Medical Center
- University Medical Center of Southern Nevada
- Nevada Cancer Research Foundation CCOP
- New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care
- New Hampshire Oncology-Hematology PA
- New Hampshire Oncology - Hematology, PA - Hooksett
- Lakes Region General Hospital
- Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
- Dartmouth Hitchcock Medical Center
- Cooper Hospital University Medical Center
- Valley Hospital - Ridgewood
- Cancer Institute of New Jersey at Cooper - Voorhees
- Mount Kisco Medical Group at Northern Westchester Hospital
- Mount Sinai Medical Center
- Wayne Memorial Hospital, Incorporated
- Kinston Medical Specialists
- Wake Forest University Health Sciences
- Medcenter One Hospital Cancer Care Center
- Mid Dakota Clinic, PC
- Sanford Bismarck Medical Center
- St. Alexius Medical Center Cancer Center
- MeritCare Broadway
- Sanford Clinic North-Fargo
- Dakota Cancer Institute at Dakota Clinic - South University
- Essentia Health Cancer Center-South University Clinic
- Sanford Medical Center-Fargo
- Sanford Roger Maris Cancer Center
- Altru Cancer Center at Altru Hospital
- Wood County Oncology Center
- Charles M. Barrett Cancer Center at University Hospital
- University of Cincinnati
- Grandview Hospital
- Good Samaritan Hospital
- David L. Rike Cancer Center at Miami Valley Hospital
- Samaritan North Cancer Care Center
- CCOP - Dayton
- Community Cancer Center
- Hematology Oncology Center
- Blanchard Valley Medical Associates
- Middletown Regional Hospital
- Atrium Medical Center-Middletown Regional Hospital
- Wayne Hospital
- Charles F. Kettering Memorial Hospital
- Lima Memorial Hospital
- Northwest Ohio Oncology Center
- St. Charles Mercy Hospital
- Toledo Clinic - Oregon
- Flower Hospital Cancer Center
- Mercy Hospital of Tiffin
- Toledo Hospital
- St. Vincent Mercy Medical Center
- Medical University of Ohio Cancer Center
- University of Toledo
- St. Anne Mercy Hospital
- Toledo Clinic Cancer Centers-Toledo
- Toledo Clinic, Incorporated - Main Clinic
- UVMC Cancer Care Center at Upper Valley Medical Center
- Fulton County Health Center
- Precision Radiotherapy at University Pointe
- Ruth G. McMillan Cancer Center at Greene Memorial Hospital
- Cancer Care Associates - Norman
- Cancer Care Associates - Mercy Campus
- Legacy Mount Hood Medical Center
- Legacy Good Samaritan Hospital and Medical Center
- Legacy Meridian Park Hospital
- Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
- Lehigh Valley Hospital - Muhlenberg
- Geisinger Medical Center
- Geisinger Medical Center-Cancer Center Hazelton
- Geisinger Medical Group
- Geisinger Wyoming Valley/Henry Cancer Center
- Rhode Island Hospital
- McLeod Regional Medical Center
- Cancer Centers of the Carolinas - Faris Road
- Cancer Centers of the Carolinas - Grove Commons
- Greenville Health System Cancer Institute-Butternut
- Greenville Health System Cancer Institute-Faris
- Greenville Hospital Cancer Center
- CCOP - Greenville
- Cancer Centers of the Carolinas - Greer Medical Oncology
- Cancer Centers of the Carolinas - Seneca
- Greenville Health System Cancer Institute-Seneca
- Cancer Centers of the Carolinas - Spartanburg
- Greenville Health System Cancer Institute-Spartanburg
- Rapid City Regional Hospital
- Sanford Cancer Center Oncology Clinic
- Avera Cancer Institute
- Sanford Cancer Center at Sanford USD Medical Center
- Fredericksburg Oncology, Incorporated
- Legacy Salmon Creek Hospital
- Gundersen Lutheran Center for Cancer and Blood
- Froedtert and the Medical College of Wisconsin
- Westfields Hospital/Cancer Center of Western Wisconsin
- Oconomowoc Memorial Hospital-ProHealth Care Inc
- Regional Cancer Center at Oconomowoc Memorial Hospital
- Waukesha Memorial Hospital Regional Cancer Center
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Arm I
Arm II
Patients receive bevacizumab on Day 1 and dasatinib on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Patients receive bevacizumab on Day 1 and placebo on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.