progressive or recurrent glioblastoma after first surgery for glioblastoma and after completion of radiotherapy MedDRA version: 9.1 Level: LLT Classification code 10018337 Term: Glioblastoma multiforme
Conditions
Interventions
Trade Name: Temodal
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Temozolomid
CAS Number: 85622-93-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
T
Sponsors
University Hospital Heidelberg, Ruprechts-Karl-University Heidelberg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Progressive or recurrent glioblastoma documented by MRI no earlier than 180 days after first surgery for glioblastoma and no earlier than 90 days after completion of radiotherapy. •Histological diagnosis of glioblastoma •Tissue available for the determination of MGMT gene promoter methylation in the recurrent tumor •Prior treatment with temozolomide administered concomitantly with radiotherapy and at least for two cycles (5/28) as an adjuvant treatment •Informed consent •Age 18-80 years •Karnofsky performance score > 50% •Neutrophil counts > 1 500/µl •Platelet counts > 100 000/µl •Hemoglobin > 10 g/dl •Serum creatinin =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: •Progressive or recurrent glioblastoma documented by MRI earlier than 180 days after first surgery for glioblastoma and earlier than 90 days after completion of radiotherapy. •Any other prior treatment than temozolomide according to the schedule of the EORTC NCIC trial (Stupp et al. N Engl J Med 2005;352:987-996) except that an adjuvant starting dose of 200 mg/m2 as well as more than 6 cycles of adjuvant temozolomide are allowed •Allergy to or other intolerability of temozolomide •Unable to undergo MRI •Prior systemic or local treatment with DNA-damaging agents, tyosine kinase inhibitors or anti-angiogenic agents for any cancer •Past medical history of diseases with poor prognosis, e.g. severe coronary heart disease, severe diabetes, immune deficiency, residual deficits after stroke, severe mental retardation •HIV infection •Pregnancy •Breast feeding •Treatment within in any other clinical trial parallel to the treatment phase of the current study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The aim of this study is to compare two regimens of dose-intensified temozolomide chemotherapy for patients with glioblastoma at first relapse or progression who have failed first-line treatment with radiotherapy plus concomitant or adjuvant temozolomide or both. Primary objective: Median time to treatment failure. Treatment failure is reached (i) upon tumor progression (ii) if treatment has to be terminated due to toxicity or (iii) if the patient dies for any reason. ;Secondary Objective: •PFS •Overall survival •Objective responses (CR and PR) •Outcome relative to MGMT promoter methylation in recurrent tumor •Outcome relative to duration of prior treatment •Outcome relative to interval from completion of prior TMZ chemotherapy treatment ( 3 months) •Toxicity •Expression of the mismatch repair genes MLH-1, MSH-2, MSH-6 und PMS2 in tumor tissue determined by immunohistochemistry •Changes in MGMT status in recurrent disease relative to initial tumor tissue if applicable •Changes in MGMT activity in peripheral blood during ongoing therapy will be assessed during the first cycle at days 1, 8, 15, 22, then MGMT activity will be investigated every 8 weeks •Quality of life determined by EORTC QoL-Brain 20 Neurotoxicity determined by MRI •Neurotoxicity determined by MMSE, MRI and NeuroCogFx neuropsychological examination •Outome relative to extent of resection •Screening for aberrant MGMT promoter methylation in peripheral blood ;Primary end point(s): Median time to treatment failure. Treatment failure is reached (i) upon tumor progression (ii) if treatment has to be terminated due to toxicity or (iii) if the patient dies for any reason. | — |
Countries
Austria, Germany
Outcome results
None listed