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Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma

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ClinicalTrials.gov Identifier: NCT00154375
Recruitment Status : Completed
First Posted : September 12, 2005
Results First Posted : February 2, 2011
Last Update Posted : April 26, 2011
Sponsor:
Information provided by:
Novartis

Tracking Information
First Submitted Date  ICMJE September 9, 2005
First Posted Date  ICMJE September 12, 2005
Results First Submitted Date  ICMJE January 13, 2011
Results First Posted Date  ICMJE February 2, 2011
Last Update Posted Date April 26, 2011
Study Start Date  ICMJE October 2004
Actual Primary Completion Date August 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 19, 2011)
Percentage of Participants With Progression Free Survival (PFS) During the Study Duration [ Time Frame: 6 months -1 year ]
PFS was defined as the time from the date of randomization to the date of the first documented progression according to the MacDonald criteria, or death due to any cause. MacDonald criteria are standard criteria in neurooncology. Tumor assessment was made according to the adapted MacDonald criteria based on the combined evaluation of 1) assessment of the MRI scan for measurable, evaluable, and new lesions (made by the independent external expert too), 2) overall assessment of neurological performance (made by the investigator), 3) concomitant steroid use (as reported by the investigator).
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 19, 2011)
Number of Participants With Death, Other Serious or Clinically Significant Adverse Events (AEs) or Related Discontinuations [ Time Frame: 6 months - 1 year ]
National Cancer Institute (NCI)/ National Institute of Health (NIH) provides a grading (severity) scale for each AE term. Grade 3 refers to severe AE and Grade 4 refers to life-threatening or disabling AE. According to FDA 21CFR 314.80, a serious adverse event (SAE) is described as any adverse event that leads to death, is life threatening ( NIH criteria Grade 4), causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event not described above.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma
Official Title  ICMJE Phase III Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma
Brief Summary This is a Phase III study comparing Imatinib mesylate and hydroxyurea combination therapy with hydroxyurea monotherapy in patients with temozolomide resistant progressive glioblastoma.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioblastoma Multiforme
  • Astrocytoma
Intervention  ICMJE
  • Drug: Imatinib mesylate
    Imatinib was supplied as 100 mg and 400 mg tablets packaged in polyethylene bottles.
    Other Name: Glivec®
  • Drug: Hydroxyurea
    Other Name: Litalir®
Study Arms  ICMJE
  • Experimental: Imatinib mesylate + hydroxyurea (HU)
    Imatinib was supplied as 100 mg and 400 mg tablets. Patients in the combination arm were instructed to take a daily oral imatinib dose of 600 mg (600 mg at lunch time) and a daily oral hydroxyurea (HU) dose of 1000 mg (500 mg twice daily; in the morning and at bed time). Every 6 weeks after randomization based on assessment of therapeutic response, either patients continued with above mentioned dosing regimen or switched to receive a daily dose of 800 mg imatinib with 1000 mg HU. Patients were instructed to split the intake, taking 400 mg imatinib with 500 mg HU in the morning, then the same in the evening.
    Interventions:
    • Drug: Imatinib mesylate
    • Drug: Hydroxyurea
  • Active Comparator: Hydroxyurea alone
    1500 mg/day of HU given as 500 mg 3 times daily. Every 6 weeks after randomization and based on assessment of therapeutic response, the patients were either switched to combination arm or continued in monotherapy arm of hydroxyurea.
    Intervention: Drug: Hydroxyurea
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 24, 2006)
240
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date August 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Signed informed consent prior to initiation of any study procedure.
  • Patients >= 18 years of age.
  • Histological confirmed diagnosis of glioblastoma multiforme / astrocytoma World Health Organization (WHO) grade IV by a reference pathologist
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
  • Adequate hepatic, renal and bone marrow function as defined by the following: total bilirubin < 1.5 x Upper Limit of Normal (ULN), ALT and AST < 2.5 x ULN, creatinine < 1.5 x ULN, absolute neutrophil count > 1.5 x109/L, platelets > 100 x109/L and hemoglobin > 10 g/dL.
  • Female patients of childbearing potential with a negative pregnancy test within 7 days of initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential who agree to employ an effective barrier method of birth control throughout the study, and for up to 3 months following discontinuation of study drug.
  • Life expectancy of >3 months.
  • MRI available every 6 weeks for disease management
  • No intercerebral inflammation
  • Irradiation therapy 54 to 62 gy finished or less according to national standard
  • Chemotherapy at least 1 temozolomide containing regimen finished, no established chemotherapy regiment available and progression under chemotherapy or in between 6 months following the last chemotherapy.
  • Leucocytes > 2.500/µl, to be controlled once a week
  • Thrombocytes > 80.000/µl, to be controlled once a week
  • Ensured compliance
  • Patients who had a second or third resection after disease progression cannot be included earlier than 2 weeks following the resection. MRI should be performed not later than 72 h post operation. If patients are to be included later than 4 weeks after the resection, a new baseline MRI must be performed.

Exclusion Criteria:

  • Female patients who are pregnant or breast-feeding.
  • Patients who have been treated with any investigational agent(s) within 28 days of the first day of administration of study drug.
  • Patients with uncontrolled medical disease such as diabetes mellitus, thyroid dysfunction, neuropsychiatric disorders, infection, angina or Grade 3 or 4 cardiac problems as defined by the New York Heart Association Criteria.
  • Patients with other malignant disorders.
  • Patient with acute or known chronic liver disease (i.e., chronic active hepatitis, cirrhosis).
  • Patients who are known to be HIV positive (no specific tests are required for confirmation of eligibility).
  • Expected incompliance according to treatment, treatment diary and examination schedule
  • Not confirmed histological diagnosis glioblastoma multiforme/astrocytoma WHO grade IV
  • Other drugs with potential cytostatic main or side effect
  • No or inadequate chemotherapy or irradiation therapy
  • Patients without hematological recovery after previous chemotherapy who have been treated with Chemotherapy within 28 days of the first day of administration of study drug.

Other protocol-specific inclusion /exclusion criteria may apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00154375
Other Study ID Numbers  ICMJE CSTI571BDE40
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party External Affairs, Novartis Pharmaceuticals
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date April 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP