Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
About
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. 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.
Full description
This trial includes a phase I dose-escalation study and a double-blind randomized phase II trial for patients with newly diagnosed glioblastoma multiforme (GBM). Phase I will be a cohort of 3 dose-escalation trial of dasatinib in combination with radiation and concomitant temozolomide. Patients receive concomitant chemotherapy and radiation therapy for cycle one. Patients receive adjuvant chemotherapy 28-42 days post cycle one treatment. Patients receive only dasatinib post cycle 8 treatment until progressive disease, unacceptable adverse events or refusal.
Phase II will be a randomized trial with two treatment arms. Patients will be randomized at the time of registration at a ratio of 1:2 respectively to either standard therapy arm (continuous daily placebo prior, during and after standard radiotherapy/temozolomide followed by temozolomide. For more information please see the Arms section. The primary objectives are listed below.
Primary Objectives:
Patients are followed for 5 years post treatment. The study permanently closed to accrual on January 31, 2014.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Pre-registration Inclusion Criteria:
Registration Inclusion Criteria:
Age ≥ 18 years
Histological Confirmation of Glioblastoma - Histologically confirmed newly diagnosed glioblastoma (GBM) (grade 4 astrocytoma) as determined by pre-registration central pathology review. Note: GBM with oligodendroglial features are not permitted in this study if they are 1p19q codeleted. Sites submitting GBM with oligodendroglial features will be asked to provide results of 1p/19q codeletion status.
Measurable or Evaluable Disease - Measurable or evaluable disease by gadolinium MRI or contrast CT scan. Note: Patients who have had a gross total resection are eligible on the basis of evaluable disease.
ECOG Performance Status 0, 1 or 2.
Required Laboratory Values:
The following laboratory values obtained ≤ 14 days prior to registration.
Required INR Value: The following INR value obtained ≤ 28 days prior to registration
Urine or Serum Pregnancy Test - Negative urine or serum pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only.
Written Informed Consent - Patient must provide written informed consent.
Return to Enrolling Institution - Patient must be willing to return to Alliance enrolling institution for follow-up.
Tissue Samples - Patient must be willing to provide tissue samples for research purposes.
Patient must be willing to provide tissue samples for research purposes.
Required Antibiotic Prophylaxis - Patient must be willing to comply with antibiotic prophylaxis with trimethoprim/sulfamethoxazole, pentamidine or dapsone.
Grapefruit and Grapefruit Juice - Patient must be willing to abstain from eating grapefruit or drinking grapefruit juice for the duration of the study treatment.
Ability to Swallow - Patient must have the ability to take oral medication (dasatinib must be swallowed whole).
Quality of Life (QOL) Questionnaires - Phase II patients only: Patients must be willing and able to complete QOL questionnaires independently or with the help of a caregiver.
Other Anti-Tumor Drug Therapies - Patient must be willing to forego other cytotoxic and non-cytotoxic drug therapy against the tumor while being treated with dasatinib and temozolomide.
Registration Exclusion Criteria:
Pregnancy, Nursing and Required Contraception - Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
Prior Radiotherapy or Chemotherapy for Any CNS Neoplasm - Received any prior radiotherapy or chemotherapy for any CNS neoplasm (hormones, vitamins and growth factors are not considered chemotherapy for the purposes of this study.
Prior Surgery for Any CNS Neoplasm - Prior surgeries for any CNS neoplasms, other than surgery related to the current GBM diagnosis. Note: If Gliadel wafers are placed at time of primary resection, this would be considered prior therapy and patient would be ineligible.
Concurrent Illness or Disease - 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. Including but not limited to:
Pleural or Pericardial Effusions - Pleural or pericardial effusion of any grade.
Immunocompromised Status - Immunocompromised patients (other than that related to the use of corticosteroids) and patients known to be HIV positive and currently receiving antiretroviral therapy. Note: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial.
Uncontrolled Intercurrent Illness - 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.
Other Investigational Agents - Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
Other Active Malignancies - Other active malignancy ≤ 5 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 Cardiac or Metabolic Conditions:
Clinically Significant Cardiovascular Disease - Patients may not have any clinically significant cardiovascular disease including the following:
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 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.
Congestive Heart Failure - New York Heart Association classification ≥ Class II Congestive Heart Failure.
Prohibited or Restricted Concomitant Treatments - Currently taking one of the following medications:
Allergy to Antibiotic Prophylaxis Medications - Severe allergy to sulfa medications and dapsone and pentamidine.
Primary purpose
Allocation
Interventional model
Masking
217 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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