Dasatinib and Bevacizumab in Treating Patients With Recurrent or Progressive High-Grade Glioma or Glioblastoma Multiforme

Glioblastoma Multiforme Clinical Trial

Official title:

Phase I/Randomized Phase II Double Blind Study of Either Dasatinib or Placebo Combined With Bevacizumab in Recurrent Glioblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00892177
• Other study ID #: NCCTG-N0872
• Secondary ID: NCI-2011-01921CD
• Status: Completed
• Phase: Phase 2
• Start date: October 2009
• Est. completion date: July 1, 2019

Study information

• Verified date: October 2019
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Bevacizumab may also block the growth of the tumor by blocking blood flow to the tumor. It is not yet known whether bevacizumab together with dasatinib are more effective than a placebo in treating patients with recurrent or progressive high-grade glioma or glioblastoma multiforme.

PURPOSE: This randomized phase I/II trial (Phase I completed) is studying the side effects and best dose of dasatinib when given together with bevacizumab and to see how well it works compared to placebo in treating patients with recurrent or progressive high-grade glioma or glioblastoma multiforme.

Description:

OUTLINE: This is a multicenter, phase I, dose-escalation study (Phase I completed) of dasatinib followed by a phase II randomized study. Patients are grouped according to study (1 vs 2). Patients in the phase II portion are stratified according to age (> 70 years of age vs ≤ 70 years of age), and ECOG performance status (0 vs 1 or 2).

Phase I: Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive oral dasatinib once or twice daily on days 1-14 until the maximum-tolerated dose (MTD) is determined. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. (Phase I completed) Please see the Arms section for the Phase II treatment regimens.

OBJECTIVES:

PRIMARY OBJECTIVES:

1. Determine the maximum tolerated dose (MTD) of dasatinib in combination with bevacizumab in high grade glioma patients. (Phase I)

2. To assess the safety and adverse events of the dasatinib in combination with bevacizumab in this patient population. (Phase I)

3. To estimate the efficacy of the bevacizumab combination with dasatinib in recurrent glioblastoma multiforme as measured by progression free survival at six months and compare it with the efficacy of bevacizumab alone. (Phase II)

SECONDARY OBJECTIVES:

1. To describe the overall toxicity associated with the dasatinib/bevacizumab combination. (Phase I)

2. To describe any preliminary evidence of antitumor activity. (Phase I)

3. To assess the time to disease progression. (Phase II)

4. To assess the safety and toxicity of the bevacizumab combination with dasatinib in this patient population. (Phase II)

5. To estimate the efficacy of the bevacizumab combination with dasatinib in recurrent glioblastoma multiforme as measured by overall survival time and compare it with the efficacy of bevacizumab alone. (Phase II)

6. To assess the impact of the treatment on the patient's quality of life (QOL) using the overall score from the FACT-Br (Phase II)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 144
• Est. completion date: July 1, 2019
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Patient Eligibility:

I. Pre-registration:

1. Central pathology review submission. This review is mandatory prior to registration to confirm eligibility.

II. Registration Inclusion Criteria:

1. =18 years of age

2. Study 1: Histologic confirmation of grade 3 or 4 glioma, including astrocytoma, oligodendroglioma, and mixed gliomas, as determined by pre-registration central pathology review.

3. Study 2: Histological confirmation of glioblastoma multiforme (grade 4 astrocytoma) as determined by pre-registration central pathology review. NOTE: Variant gliosarcomas are eligible

4. 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.

5. Bidimensionally measurable or evaluable disease by MRI or CT scan.

6. ECOG Performance Status (PS) 0, 1, or 2.

7. Patient willing to discontinue use of aspirin or medications that inhibit platelet function = 1 week prior to registration.

8. Previous RT and =12 weeks since the completion of RT prior to registration.

9. 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

10. 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

11. Negative pregnancy test done =7 days prior to registration, for women of childbearing potential only.

12. Ability to complete questionnaire(s) by themselves or with assistance.

13. Provide informed written consent

14. Willingness to return to enrolling institution for follow-up.

15. Patient willing to provide mandatory tissue samples for research purposes

16. 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:

1. 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.

2. 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.

3. Prior treatment with bevacizumab or VEGF-Trap (Aflibercept).

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. Evidence of bleeding diathesis (greater than normal risk of bleeding) or coagulopathy (in the absence of therapeutic anticoagulation).

10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.

11. Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.

12. 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.

13. History of myocardial infarction or unstable angina =6 months prior to registration.

14. New York Heart Association (NYHA) classification II, III or IV congestive heart failure.

15. Core biopsy or other minor surgical procedures =7 days prior to registration. Note:

Placement of a vascular access device is allowed.

16. 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.

17. Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis =6 months prior to registration.

18. History of hypertensive crisis or hypertensive encephalopathy.

19. Known hypersensitivity to any of the components of dasatinib or bevacizumab.

20. Serious, non-healing wound, active ulcer, or untreated bone fracture

21. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess =6 months prior to registration.

22. Active or recent history of hemoptysis (= ½ teaspoon of bright red blood per episode) =30 days prior to registration.

23. History of stroke or transient ischemic attack (TIA) =6 months prior to registration.

24. Any evidence of CNS hemorrhage on baseline CT or MRI

25. 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

26. Diagnosed congenital long QT syndrome

27. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes)

28. Prolonged QTc interval on pre-entry electrocardiogram (>450 msec)

29. 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.

30. Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration

31. Known pleural or pericardial effusion of any grade

32. Concomitant use of H2 blockers or proton pump inhibitors that cannot be discontinued or switched to locally acting agents (i.e. famotidine or omeprazole.)

33. 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®).

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

Biological:
• bevacizumab
Given intravenously

Drug:
• dasatinib
Given orally

Other:
• placebo
Given orally

Locations

Country	Name	City	State
United States	Kapiolani Medical Center at Pali Momi	'Aiea	Hawaii
United States	Oncare Hawaii, Incorporated - Pali Momi	'Aiea	Hawaii
United States	Bixby Medical Center	Adrian	Michigan
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	Toledo Clinic Cancer Centers - Adrian	Adrian	Michigan
United States	Toledo Clinic Cancer Centers-Adrian	Adrian	Michigan
United States	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania
United States	McFarland Clinic, PC	Ames	Iowa
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	Aurora Presbyterian Hospital	Aurora	Colorado
United States	Rush-Copley Cancer Care Center	Aurora	Illinois
United States	CancerCare of Maine at Eastern Maine Medical Center	Bangor	Maine
United States	MeritCare Bemidji	Bemidji	Minnesota
United States	Sanford Clinic North-Bemidji	Bemidji	Minnesota
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Billings Clinic	Billings	Montana
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Frontier Cancer Center and Blood Institutes-Billings	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota
United States	Mid Dakota Clinic, PC	Bismarck	North Dakota
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota
United States	Illinois CancerCare - Bloomington	Bloomington	Illinois
United States	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	Boulder Community Hospital	Boulder	Colorado
United States	Boulder Community Hospital	Boulder	Colorado
United States	Wood County Oncology Center	Bowling Green	Ohio
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Illinois CancerCare - Canton	Canton	Illinois
United States	Illinois CancerCare - Carthage	Carthage	Illinois
United States	Cedar Rapids Oncology Association	Cedar Rapids	Iowa
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Rush University Medical Center	Chicago	Illinois
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa
United States	Mercy Cancer Center - West Lakes	Clive	Iowa
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	John B Amos Cancer Center	Columbus	Georgia
United States	New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care	Concord	New Hampshire
United States	New Hampshire Oncology-Hematology PA	Concord	New Hampshire
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - St. Luke's Medical Center	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	St. Anthony Central Hospital	Denver	Colorado
United States	St. Joseph Hospital	Denver	Colorado
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	CCOP - Duluth	Duluth	Minnesota
United States	Essentia Health - Duluth Clinic	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller - Dwan Medical Center	Duluth	Minnesota
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	Community Cancer Center	Elyria	Ohio
United States	Hematology Oncology Center	Elyria	Ohio
United States	Swedish Medical Center	Englewood	Colorado
United States	Eureka Community Hospital	Eureka	Illinois
United States	Illinois CancerCare - Eureka	Eureka	Illinois
United States	Dakota Cancer Institute at Dakota Clinic - South University	Fargo	North Dakota
United States	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota
United States	MeritCare Broadway	Fargo	North Dakota
United States	Sanford Clinic North-Fargo	Fargo	North Dakota
United States	Sanford Medical Center-Fargo	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Hurley Medical Center	Flint	Michigan
United States	McLeod Regional Medical Center	Florence	South Carolina
United States	Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota
United States	Saint Francis Cancer Treatment Center at Saint Francis Memorial Health Center	Grand Island	Nebraska
United States	Benefis Healthcare - Sletten Cancer Institute	Great Falls	Montana
United States	Benefis Sletten Cancer Institute	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Cancer Centers of the Carolinas - Faris Road	Greenville	South Carolina
United States	Cancer Centers of the Carolinas - Grove Commons	Greenville	South Carolina
United States	CCOP - Greenville	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Butternut	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Faris	Greenville	South Carolina
United States	Greenville Hospital Cancer Center	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Cancer Centers of the Carolinas - Greer Medical Oncology	Greer	South Carolina
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Illinois CancerCare - Havana	Havana	Illinois
United States	Geisinger Medical Center-Cancer Center Hazelton	Hazleton	Pennsylvania
United States	St. Peter's Hospital	Helena	Montana
United States	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida
United States	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Kuakini Medical Center	Honolulu	Hawaii
United States	Oncare Hawaii Inc-POB II	Honolulu	Hawaii
United States	OnCare Hawaii, Incorporated - Kuakini	Honolulu	Hawaii
United States	OnCare Hawaii, Incorporated - Lusitana	Honolulu	Hawaii
United States	Queen's Cancer Institute at Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital, Incorporated	Honolulu	Hawaii
United States	University of Hawaii	Honolulu	Hawaii
United States	New Hampshire Oncology - Hematology, PA - Hooksett	Hooksett	New Hampshire
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	St. Francis Hospital Cancer Care Services	Indianapolis	Indiana
United States	Foote Memorial Hospital	Jackson	Michigan
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida
United States	Castle Medical Center	Kailua	Hawaii
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Illinois CancerCare - Kewanee Clinic	Kewanee	Illinois
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Kinston Medical Specialists	Kinston	North Carolina
United States	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	Lakes Region General Hospital	Laconia	New Hampshire
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Beebe Medical Center	Lewes	Delaware
United States	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware
United States	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas
United States	Kauai Medical Clinic	Lihue	Hawaii
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Lima Memorial Hospital	Lima	Ohio
United States	Cancer Resource Center - Lincoln	Lincoln	Nebraska
United States	Nebraska Cancer Research Center	Lincoln	Nebraska
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado
United States	McKee Medical Center	Loveland	Colorado
United States	Illinois CancerCare - Macomb	Macomb	Illinois
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology - Maplewood	Maplewood	Minnesota
United States	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Illinois CancerCare - Monmouth	Monmouth	Illinois
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital - Monroe	Monroe	Michigan
United States	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan
United States	Mount Kisco Medical Group at Northern Westchester Hospital	Mount Kisco	New York
United States	Westfields Hospital/Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Mount Sinai Medical Center	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Illinois CancerCare - Community Cancer Center	Normal	Illinois
United States	Cancer Care Associates - Norman	Norman	Oklahoma
United States	Callahan Cancer Center at Great Plains Regional Medical Center	North Platte	Nebraska
United States	Oconomowoc Memorial Hospital-ProHealth Care Inc	Oconomowoc	Wisconsin
United States	Regional Cancer Center at Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Cancer Care Associates - Mercy Campus	Oklahoma City	Oklahoma
United States	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Immanuel Medical Center	Omaha	Nebraska
United States	Lakeside Hospital	Omaha	Nebraska
United States	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Toledo Clinic - Oregon	Oregon	Ohio
United States	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	Illinois CancerCare - Pekin	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois CancerCare - Peru	Peru	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	Palchak David MD	Pismo Beach	California
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	Saint Joseph Mercy Port Huron	Port Huron	Michigan
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Illinois CancerCare - Princeton	Princeton	Illinois
United States	Rhode Island Hospital	Providence	Rhode Island
United States	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	Valley Hospital - Ridgewood	Ridgewood	New Jersey
United States	Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	CentraCare Clinic - River Campus	Saint Cloud	Minnesota
United States	Coborn Cancer Center	Saint Cloud	Minnesota
United States	Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	Regions Hospital Cancer Care Center	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	Cancer Centers of the Carolinas - Seneca	Seneca	South Carolina
United States	Greenville Health System Cancer Institute-Seneca	Seneca	South Carolina
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Cancer Centers of the Carolinas - Spartanburg	Spartanburg	South Carolina
United States	Greenville Health System Cancer Institute-Spartanburg	Spartanburg	South Carolina
United States	Illinois CancerCare - Spring Valley	Spring Valley	Illinois
United States	Geisinger Medical Group	State College	Pennsylvania
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	St. Anne Mercy Hospital	Toledo	Ohio
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio
United States	Toledo Hospital	Toledo	Ohio
United States	University of Toledo	Toledo	Ohio
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Legacy Salmon Creek Hospital	Vancouver	Washington
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	St. John Macomb Hospital	Warren	Michigan
United States	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia
United States	Waukesha Memorial Hospital Regional Cancer Center	Waukesha	Wisconsin
United States	Fulton County Health Center	Wauseon	Ohio
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Precision Radiotherapy at University Pointe	West Chester	Ohio
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
United States	Associates in Women's Health - Wichita	Wichita	Kansas
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas - Main Office	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Minnesota Oncology - Woodbury	Woodbury	Minnesota
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Dose Limiting Toxicities to Determine Maximum Tolerated Dose (MTD) of Dasatinib in Combination With Bevacizumab (Phase I)	The Maximum Tolerated Dose (MTD) will be based on the assessment of dose-limiting toxicities (DLT) during the first 4 weeks of treatment only (i.e., following the first 2 treatment cycles), and will be defined as the dose at which fewer than one-third of patients experience a DLT to study treatment. The MTD is the dose level at which 0/6 or 1/6 patients experience DLT with the next higher dose having at least 2 out of 3 or 2 out of 6 patients encountering DLT.; > Three patients will be treated at each dose level, and can be enrolled simultaneously. If one DLT is encountered, an additional 3 patients will be added to that dose level. If at any point two DLTs are encountered within a given dose level, then the MTD has been exceeded and if only three patients have been treated at the next lower dose three more patients are treated at the next lower dose. The number of patients who developed DLTs are reported here by dose level, with the MTD reported in the statistical analysis section.	14 days
Primary	Progression-free Survival at 6 Months (PFS6) (Phase II)	The primary endpoint is the proportion of patients alive and progression-free 6 months after study treatment initiation (PFS6). All eligible consented patients that received treatment will be considered evaluable. Those who die will be considered to have had disease progression unless documented evidence clearly indicates no progression has occurred. PFS6 is defined as the time from start of study therapy to the date of first observation of disease progression or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The PFS6 will be estimated as the number of evaluable patients progression free and still alive at 6 months divided by the total number of evaluable patients. The confidence interval will be calculated according to the Clopper-Pearson Method.	6 months
Secondary	Number of Participants With Adverse Events According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 (Phase II)	Adverse events were collected systematically at the end of each cycle and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0. Events are scored as: 1="Mild symptoms", 2= "Moderate", 3="Severe", 4="Life-threatening", and 5="Death". The number of patients reporting a grade 3 or higher event regardless of attribution are summarized here. A complete list of all adverse events reported during treatment can be found in the Adverse Events Section.	Up to 3 years
Secondary	Overall Survival (Phase II)	Survival time is defined to be the length of time from start of study therapy to death due to any cause. All patients meeting the eligibility criteria that have signed a consent form and begun treatment will be considered evaluable for estimation of the survival distribution. The distribution of overall survival for both arms of the study will be estimated using the Kaplan-Meier method, and be compared using log-rank tests.	Up to 3 years
Secondary	Time-to-disease Progression (Phase II)	Time-to-disease progression is defined as the time from start of study therapy to documentation of disease progression. Patients who die without documentation of progression will be considered to have had tumor progression at the time of death unless there is documented evidence that no progression occurred before death. Patients who fail to return for evaluation after beginning therapy will be censored for progression on the last day of therapy or date last known to be alive, whichever is later. Patients who are still alive and have not progressed will be censored for progression at the time of the last tumor assessment. Patients who experience major treatment violations will be censored for progression on the date the treatment violation occurred. The time-to-progression distribution will be estimated using the Kaplan-Meier method.	Up to 3 years
Secondary	Patient-reported QOL, as Measure by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) (Phase II)	FACT-Br questionnaires were used to assess QOL at every other cycle of treatment (prior to cycles 3, 5, 7, etc.). FACT-Br includes 50 questions used to assess patients' self-assessment in 4 broad categories: Physical, Social/Family, Emotional, and Function Well-being. Scores range from 0="Not at all", 1="A little bit", 2="Somewhat", 3="Quite a bit", 4="Very Much". Higher scores can be interpreted as having higher quality of life. The scores for all 50 questions were summed to give a total score per patient per cycle. Therefore the possible range is from 0 to 200. Below is the reported mean and standard deviation for patients at baseline and during cycles 2, 4, 6, 8, and 10.	Baseline to cycle 10 (20 weeks).
Secondary	Objective Response (Phase II)	Objective response to treatment will be determined by the results of neurological exam and the MRI and/or CT measurement of the tumor at each evaluation as is used for all NCCTG neuro-oncology trials. The percentage of patients in each response category will be summarized, 95% confidence intervals calculated, and rates between the 2 arms will be compared using a Fisher's Exact test. For bi-dimensionally measurable disease, CR: total disappearance of all tumor and that patients be on no corticosteroids or on only adrenal replacement maintenance; PR: = 50% reduction in product of perpendicular diameters of contrast enhancement or mass with no new lesions, and stable or decreasing steroid dosing; PD: >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions; REGR: unequivocal reduction in extent of contrast-enhancement, or a decrease in mass effect, no new lesions (for evaluable disease); SD: failure to qualify for CR, PR,REGR or PD.	Up to 3 years