A phase II, open-label, multi-centre, single-arm study, evaluating the efficacy of Glivec® plus Hydroxyurea (HU) in patients with progressive glioblastoma multiforme (GBM), not receiving enzyme inducing anticonvulsant drugs (EIACDs).
- Conditions
- progressive glioblastoma multiforme (GBM) following failure of front-line therapy defined to include surgery, radiotherapy and exposure to temozolomide chemotherapy regimen.
- Registration Number
- EUCTR2005-002600-41-DK
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 110
Waivers for protocol eligibility will not be granted. Patients must be fully eligible and have all pre-testing in place to enter the study within the specified period.
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 must have measurable disease on gadolinium enhanced MRI
Patients taking steroids: must have been on stable dose for 7 days or more
ECOG performance score greater than or equal to 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 equal or greater than 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 to visit 1 (start of study drug).
Patients with a life expectancy of at least 8 weeks.
Signed informed consent be the patient prior to patient entry and any study procedure.
Are the trial subjects under 18?
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Patients who have received previous imatinib or hydroxyurea prior to study entry, or any investigational agent within the last 6 months
Patients who have had a second course 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 who are currently taking EIACDs (such as carbamazepine, phenobarbital, phenytoin, phosphenytoin, oxcarbamazepine, primadone). Previous EIACD should have been interrupted 4 weeks prior to study start.
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 who received chemotherapy within 4 weeks prior to study start (6 weeks for nitrosourea) or who have not recovered from the toxic effects of such therapy.
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 claustrophobia or physically unable to fit into the machine (e.g. obesity etc.).
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method