Investigational study to assess the overall response (OR) rate (CR + PR) of Imatinib mesylate
and Hydroxyurea (Hydroxycarbamide) combination therapy on patients with recurrent
glioblastoma multiforme (brain tumors). This study will also evaluate duration of tumor
response (as per MacDonald criteria), clinical benefit, progression free survival rate at 6
and 12 month for the combined treatment and the survival rate at 12 and 24 months.
Inclusion criteria:
- Patients must have histologically confirmed diagnosis of progressive primary GBM based
on original diagnosis. Original histology slides must be available for central
diagnostic review. Patients with prior low-grade glioma are eligible if histological
re-assessment demonstrates transformation to GBM. The most recent histology slides or
biopsy sample must be available for central diagnostic review.
- Patients must have no more than one prior episode of progressive disease following
previously received surgery and/or radiation and only one prior chemotherapy exposure
of either Temozolomide or nitrosourea. The chemotherapy could have been administered
either in an adjuvant or later setting. The application of Gliadel wafers will be
considered a regimen of nitrosourea chemotherapy.
- Patients who are currently taking EIACDs (such as carbamazepine, phenobarbital,
phenytoin, fosphenytoin, oxcarbazepine, primidone).
- Patients must have measurable disease on gadolinium enhanced MRI
- Patients taking steroids: must have been on stable dose for ≥ 7 days
- ECOG performance score <= 2
- Hemoglobin ≥ 10g/dL (or Hematocrit > 29%), ANC > 1,500 cells/l, platelets > 100,000
cells/l.
- Serum creatinine < 1. 5 mg/dl, BUN < 25 mg/dl, serum SGOT and bilirubin < 1. 5 times
upper limit of normal.
- Male and female patients with age ≥ 18 years.
- Male and female patients who are sexually active must use double-barrier
contraception, oral contraceptive plus barrier contraceptive, or must have undergone
clinically documented total hysterectomy and/or ovariectomy, or tubal ligation.
- Female patients of child bearing potential must have had a negative pregnancy test
within 48 hours prior to visit 1 (start of study drug).
- Patients with a life expectancy of at least 8 weeks
- Signed informed consent by the patient prior to patient entry and any study procedure
Exclusion criteria:
- Patients who have received previous imatinib or hydroxyurea prior to study entry or
any investigational agent within the last six months
- Patients who have had a second regimen of chemotherapy
- Patients who have had a second course of radiotherapy are excluded, unless this was
given as a single, localized application of radiosurgery
- Patients with ≥ grade 2 peripheral edema, or pulmonary or pericardial effusions or
ascites of any grade
- Patients who are not a minimum of 12 weeks from completion of conventional external
beam radiotherapy unless:
- there is new radiographical enhancement outside the field of radiation,
- or there is new pathological confirmation of recurrent tumor
- or progressive radiographical enhancement noted on post-RT/TMZ continues to
worsen after an additional course of TMZ.
- Patients who have an excessive risk of an intracranial hemorrhagic event (defined by
stroke within the prior 6 months, history of CNS (excluding post-operative grade 1) or
intraocular bleed.
- Patients who have any uncontrolled systemic infection.
- Patients with evidence of intra-tumor hemorrhage on pretreatment diagnostic imaging,
except for stable post-operative grade 1 hemorrhage.
- Patients who have had major surgery within 2 weeks prior to study entry, or who have
not recovered from prior major surgery.
- Patients within three months following second surgery for progressing GBM, unless an
immediate postoperative scan is made demonstrating measurable disease that is now
progressing.
- Patients who received chemotherapy within 4 weeks prior to study start (6 weeks for
nitrosourea) or other investigational agents (biological, immunotherapeutic or
cytostatic agents) prior to study start, or who have not recovered from the toxic
effects of such therapy. Other investigational agents or targeted agents may be
employed with the chemotherapy mentioned above, but the use of such agents separately
will be considered a second regimen and render the patient ineligible for this
protocol.
- Patients with an impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of imatinib
- Patients who are taking Coumadin (warfarin sodium).
- For the purposes of MRI Imaging, patients with a pacemaker; ferromagnetic metal
implants other than those approved as safe for use in MR scanners (e. g. some types of
aneurysm clips, shrapnel); patients suffering from uncontrollable - Patients with
another primary malignancy treated within the prior three years except excised
squamous cell carcinomas of the skin and carcinoma in situ lesions of other organs
which have been treated for cure.
- Patients with a known history of Human Immunodeficiency Virus (HIV) seropositivity;
testing for HIV is not required at study entry.
- Patients who are considered by the investigator as unlikely to be able to be compliant
with the study, take the study medications, travel for the necessary assessment
visits, or have other medical conditions likely to interfere with the study
assessments should not be entered onto the trial.
- Patients who are not able to provide reliable informed consent and who do not have a
legal representative for healthcare decisions on their behalf should not be entered
onto the protocol.
Other protocol-specific inclusion / exclusion criteria may apply.
