Efficacy and Safety Study of Lomustine/Temozolomide Combination Therapy vs. Standard Therapy for Glioblastoma Patients
Status:
Completed
Trial end date:
2017-04-06
Target enrollment:
Participant gender:
Summary
The prognosis of patients with newly diagnosed glioblastoma is dismal despite recent
therapeutic improvements Using standard therapy with temozolomide (TMZ) and radiotherapy (60
Gy), the median overall survival time (mOS) is 14.6 months (Stupp et al., 2005). Since in a
previous non-randomized bicentric phase II trial, primary combination chemotherapy with
lomustine (CCNU) and TMZ was highly effective (mOS 23 months; UKT-03 trial; Herrlinger et
al., 2006; Glas et al., 2009) the proposed trial further investigates the efficacy of
CCNU/TMZ in a randomized multicenter phase III setting against standard therapy. In case the
projected phase III trial confirms the phase II data, CCNU/TMZ combination would be
significantly better than TMZ monotherapy and would thus be the new standard treatment for
newly diagnosed GBM patients with a methylated MGMT promotor. Thus, this trial has the
potential to profoundly change the standard therapy of this most aggressive brain tumor.
Since in the previous trial only patients with a methylated MGMT (mMGMT) promoter had a
benefit from CCNU/TMZ (mOS in the mMGMT group 34 months, in the non-mMGMT group 12.5 months;
Glas et al., 2009) while patients with a non-methylated MGMT did not have any benefit, the
trial is restricted to mMGMT patients.The CeTeG trial randomizes in a 1:1 fashion newly
diagnosed GBM patients (18-70 years) for either standard TMZ therapy (concomitant and 6
courses à 4 weeks of adjuvant TMZ therapy) or experimental CCNU/TMZ therapy (6 courses à 6
weeks). Both arms include standard radiotherapy (RT) of the tumor site (30 x 2 Gy). Assuming
that CCNU/TMZ therapy increases the median overall survival (mOS) from 48.9% (standard TMZ)
to 70% (CCNU/TMZ; 75% in the previous phase II trial, Glas et al., 2009), 2 x 68 patients
have to be accrued. Patients will be accrued over 24 months and each patient will be followed
for at least 24 months adding up to a total minimal duration of the time from first patient
in until the end of the follow-up time of 48 months. The primary endpoint is overall
survival; secondary endpoints include progression-free survival, response rate, acute and
late toxicity, and quality of life.