Dasatinib or Placebo, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

This study is currently recruiting participants.
Verified February 2013 by National Cancer Institute (NCI)
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00869401
First received: March 25, 2009
Last updated: February 17, 2013
Last verified: February 2013
  Purpose

RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It may also make tumor cells more sensitive to radiation therapy. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This randomized phase I/II trial is studying the best dose of dasatinib and to see how well it works compared with a placebo when given together with radiation therapy and temozolomide in treating patients with newly diagnosed glioblastoma multiforme.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: dasatinib
Drug: temozolomide
Other: placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Phase I/Randomized Phase II Trial of Either Dasatinib or Placebo Combined With Standard Chemo-Radiotherapy for Newly Diagnosed Glioblastoma Multiforme (GBM)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time-to-disease progression [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Objective response [ Designated as safety issue: No ]
  • Adverse events as assessed by NCI CTCAE version 3.0 [ Designated as safety issue: Yes ]
  • Association between biomarkers and antitumor activity/patient outcomes [ Designated as safety issue: No ]
  • Relationships among the relevant mutations/activity indicators of biomarkers and clinical outcomes [ Designated as safety issue: No ]
  • Correlations between molecular profiles and clinical outcomes for combinations and for individual agents within combinations [ Designated as safety issue: No ]
  • Clinical outcomes for subsets of patients defined by the biomarker variables [ Designated as safety issue: No ]
  • Quality of life as assessed by FACT-BR, EORTC QLQ-C15-PAL, and EORTC QLQ-BN20 questionnaires at baseline and courses 4, 6, 8, 10, and 12 [ Designated as safety issue: No ]

Estimated Enrollment: 217
Study Start Date: June 2009
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (Phase II)
Patients receive oral dasatinib once daily and oral temozolomide once daily on days 1-42. Patients undergo external-beam radiotherapy (EBRT), including intensity-modulated radiotherapy, 5 days a week for 6 weeks. Beginning 28-42 days after course 1, patients receive oral dasatinib once daily on days 1-28 and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: dasatinib
Given orally
Drug: temozolomide
Given orally
Active Comparator: Arm II (Phase II)
Patients receive oral placebo once daily on days 1-42 and temozolomide as in arm I. Patients also undergo EBRT as in arm I. Beginning 28-42 days after course 1, patients receive oral placebo once daily on days 1-28 and temozolomide as in arm I. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: temozolomide
Given orally
Other: placebo
Given orally

  Show Detailed Description

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed glioblastoma multiforme (GBM)

    • Grade 4 astrocytoma
    • No grade 4 oligoastrocytoma or GBM with oligodendroglial features
  • Newly diagnosed disease
  • Measurable or evaluable disease by gadolinium MRI or contrast CT scan

    • Patients who have had a gross total resection are eligible on the basis of evaluable disease
  • No pleural or pericardial effusion of any grade
  • No prior surgery for CNS neoplasms other than surgery related to the current GBM diagnosis

    • If Gliadel wafers are placed at time of primary resection this would be considered prior therapy and patient would be ineligible

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Absolute neutrophil count (ANC) ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin > 9.0 g/dL
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST ≤ 2.5 times ULN
  • Creatinine ≤ 1.5 times ULN
  • INR ≤ 1.5
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 12 weeks after completion of study treatment
  • No immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be HIV positive and currently receiving antiretroviral therapy

    • Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
  • No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • No history of any of the following conditions:

    • Congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
    • Congenital long QT syndrome
    • Clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
    • Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec)
    • Hypokalemia or hypomagnesemia
  • Patients may not have any clinically significant cardiovascular disease including the following:

    • Myocardial infarction or ventricular tachyarrhythmia within 6 months
    • Ejection fraction less than institutional normal
    • Major conduction abnormality (unless a cardiac pacemaker is present)
    • New York Heart Association classification ≥ class II congestive heart failure
    • 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

      • Patients with underlying cardiopulmonary dysfunction should be excluded from the study
  • No comorbid systemic illnesses or other severe concurrent disease that, 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 including, but not limited to, any of the following:

    • History of bleeding diathesis
    • Concurrent chronic systemic anticoagulation therapy that can not be discontinued (i.e., antiplatelet agents or aspirin)
    • Concurrent t chronic nonsteroidal anti-inflammatory drugs (NSAIDs) that cannot be discontinued
  • No other active malignancy ≤ 5 years prior to registration

    • Exceptions: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
    • If there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer
  • No severe allergy to sulfa medications and dapsone
  • Able to tolerate either intravenous or inhaled dapsone
  • Able to take oral medication
  • Willingness to abstain from eating grapefruit or drinking grapefruit juice for the duration of the study treatment

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • See Patient Characteristics
  • At least 5 days since prior and no concurrent St. John wort
  • No prior radiotherapy or chemotherapy for any CNS neoplasm (hormones, vitamins, and growth factors are not considered chemotherapy for the purposes of this study)
  • At least 7 days, but < 42 days, since prior stereotactic biopsy
  • At least 14 days, but < 42 days, since prior open craniotomy
  • Willing to forego other cytotoxic and non-cytotoxic drug therapy against the tumor while being treated with dasatinib and temozolomide
  • No other concurrent investigational agent considered as treatment for the primary neoplasm
  • Must not be currently taking any of the following medications:

    • Enzyme-inducing anticonvulsants (EIACs)

      • To be eligible, patient must be switched to non-EIAC medications ≥ 7 days prior to registration
    • Potent inhibitors of CYP3A4 that cannot be discontinued
    • Medications that may possibly prolong QT interval and produce a QTc that is ≥ 60 msec or a QTcF that is ≥ 450 msec
    • H2 blockers or proton pump inhibitors (PPIs), such as famotidine (Pepcid) and omeprazole (Prilosec) respectively, that cannot be discontinued or switched to locally acting agents, such as Maalox, Mylanta, or TUMS
  • No concurrent treatment immunosuppressive agent, except corticosteroids
  • No concurrent other anticancer agents
  • No concurrent prophylactic leukocyte growth factors (e.g., filgrastim [G-CSF] and sargramostim [GM-CSF])
  • No concurrent live vaccines
  • No concurrent therapeutic anticoagulation with warfarin
  • No concurrent ibuprofen or other nonsteroidal anti-inflammatory drugs (NSAIDs)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00869401

  Show 207 Study Locations
Sponsors and Collaborators
North Central Cancer Treatment Group
Investigators
Study Chair: Nadia N. Laack, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Jan C. Buckner, North Central Cancer Treatment Group
ClinicalTrials.gov Identifier: NCT00869401     History of Changes
Other Study ID Numbers: CDR0000637854, NCCTG-N0877
Study First Received: March 25, 2009
Last Updated: February 17, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
adult giant cell glioblastoma
adult glioblastoma
adult gliosarcoma

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
Temozolomide
Dacarbazine
Dasatinib
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014