Trial record 1 of 1 for:    NCT00892177
Previous Study | Return to List | Next Study

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Alliance for Clinical Trials in Oncology
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology ( North Central Cancer Treatment Group )
ClinicalTrials.gov Identifier:
NCT00892177
First received: May 1, 2009
Last updated: September 17, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Biological: bevacizumab
Drug: dasatinib
Other: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Phase I/Randomized Phase II Double Blind Study of Either Dasatinib or Placebo Combined With Bevacizumab in Recurrent Glioblastoma

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • MTD of dasatinib in combination with bevacizumab (Phase I) [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
  • Proportion of patients alive and progression-free (Phase II) [ Time Frame: 6 months post-treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Time-to-disease progression [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Patient-reported QOL [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 183
Study Start Date: October 2009
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive bevacizumab as in phase I and dasatinib at the MTD as determined in phase I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Biological: bevacizumab
Given intravenously
Drug: dasatinib
Given orally
Experimental: Arm II
Patients receive bevacizumab as in phase I and oral placebo once or twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Biological: bevacizumab
Given intravenously
Other: placebo
Given orally

Detailed 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)

Phase II (patients are randomized to 1 of 2 treatment arms):

  • Arm I: Patients receive bevacizumab as in phase I and dasatinib at the MTD as determined in phase I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive bevacizumab as in phase I and oral placebo once or twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed by FACT-Br questionnaire at baseline and prior to every other course (no longer assessed as of 5/18/2009)(newly added as of 2/2/2010). Tissue samples are collected at baseline for biomarker studies and assessed by IHC, RT-PCR, and FISH. Patients undergo dynamic contrast-enhanced MRI at baseline, day 3 of course 1, and day 1 of course 2.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)

After completion of study therapy, patients are followed up periodically for up to 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Phase I: Histologic confirmation of grade 3 or 4 glioma, including astrocytoma, oligodendroglioma, and mixed gliomas, as determined by pre-registration central pathology review
Phase II: 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 magnetic resonance imaging (MRI) or computed tomography (CT) scan; Note: Patients who have had surgical treatment at recurrence are eligible if they had a subtotal resection with measurable or non-measurable residual disease on postoperative imaging or if there is imaging evidence of disease progression as compared to the first postoperative scan
  • Measurable or evaluable disease by MRI or CT scan; Note: Patients who have had a gross total resection (GTR) are eligible on the basis of evaluable disease
  • 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 radiation therapy (RT) and >= 12 weeks since the completion of RT prior to registration
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin > 9.0 g/dL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x ULN
  • Creatinine =< ULN
  • Urine protein:creatinine (UPC) ratio < 1; NOTE: Urine protein must be screened by urine analysis for 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 written informed consent
  • Willingness to return to Alliance enrolling institution for follow-up
  • Patient willing to provide mandatory tissue samples for research purposes
  • Phase I: Any number of prior chemotherapy regimens for recurrent disease
Phase II: Up to 2 prior chemotherapy regimens with =< 1 regimen for recurrent disease •>= 4 weeks from prior chemotherapy, small molecule cell cycle inhibitors or other investigational agents (>= 6 weeks from nitrosoureas) at the time of registration

Exclusion Criteria:

Any of the following: 


  • Pregnant women

  • Nursing women

  • 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

    • 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 positron emission tomography (PET) scan
    • Prior treatment with bevacizumab or vascular endothelial growth factor (VEGF)-Trap (aflibercept)
    • Inadequately controlled hypertension (systolic blood pressure of > 150 mm Hg or diastolic pressure > 100 mm Hg 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 human immunodeficiency virus (HIV) positive, but without clinical evidence of an immunocompromised state, are eligible for this study
    • Any condition (i.e., 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 international normalized ratio (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, nonhealing 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 central nervous system (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 corrected QT (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 (PPIs) 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)
  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: NCT00892177

  Show 308 Study Locations
Sponsors and Collaborators
North Central Cancer Treatment Group
Investigators
Study Chair: Evanthia Galanis, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Alliance for Clinical Trials in Oncology ( North Central Cancer Treatment Group )
ClinicalTrials.gov Identifier: NCT00892177     History of Changes
Other Study ID Numbers: NCCTG-N0872, NCI-2011-01921, CDR0000641746
Study First Received: May 1, 2009
Last Updated: September 17, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Alliance for Clinical Trials in Oncology:
adult giant cell glioblastoma
adult glioblastoma
adult gliosarcoma
adult mixed glioma
recurrent adult brain tumor
adult anaplastic oligodendroglioma
adult oligodendroglioma
adult anaplastic astrocytoma

Additional relevant MeSH terms:
Glioblastoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Bevacizumab
Dasatinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 26, 2014