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Trial record 1 of 1 for:    NCT00892177
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Dasatinib and Bevacizumab in Treating Patients With Recurrent or Progressive High-Grade Glioma or Glioblastoma Multiforme

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00892177
First received: May 1, 2009
Last updated: July 30, 2014
Last verified: July 2014
  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
Glioblastoma Multiforme
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 ] [ 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 3 years ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Time-to-disease progression [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Patient-reported QOL [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Objective response [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Enrollment: 183
Study Start Date: October 2009
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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.
Biological: bevacizumab
Given intravenously
Drug: dasatinib
Given orally
Active Comparator: Arm II
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.
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) 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)
  Eligibility

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

  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®).
  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 307 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Study Chair: Evanthia Galanis, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Alliance for Clinical Trials in Oncology
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: July 30, 2014
Health Authority: United States: Food and Drug Administration

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
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Bevacizumab
Dasatinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014