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Efficacy and Safety Study of Lomustine/Temozolomide Combination Therapy vs. Standard Therapy for Glioblastoma Patients (CeTeG)

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ClinicalTrials.gov Identifier: NCT01149109
Recruitment Status : Completed
First Posted : June 23, 2010
Last Update Posted : June 14, 2017
Sponsor:
Information provided by (Responsible Party):
Ulrich Herrlinger, University Hospital, Bonn

Tracking Information
First Submitted Date  ICMJE June 14, 2010
First Posted Date  ICMJE June 23, 2010
Last Update Posted Date June 14, 2017
Study Start Date  ICMJE October 2010
Actual Primary Completion Date April 6, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 22, 2010)
overall survival [ Time Frame: after follow up (4 years) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 22, 2010)
  • progression free survival [ Time Frame: after follow up (4 years) ]
  • best response rate determined by MRI [ Time Frame: after follow up (4 years) ]
  • frequency of delay of the next Lomustine/Temozolomide or Temozolomide course [ Time Frame: during treatment period (2 years) ]
  • acute toxicity during radiotherapy and chemotherapy according to CTC AE V3.0 [ Time Frame: during treatment period (2 years) ]
  • quality of life [ Time Frame: including follow up (4 years) ]
  • Evaluation of late neurotoxicity [ Time Frame: after follow up (4 years) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety Study of Lomustine/Temozolomide Combination Therapy vs. Standard Therapy for Glioblastoma Patients
Official Title  ICMJE Phase III Trial of CCNU/Temozolomide (TMZ) Combination Therapy vs. Standard TMZ Therapy for Newly Diagnosed MGMT-methylated Glioblastoma Patients
Brief 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.
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
Intervention  ICMJE
  • Drug: Temozolomide and lomustine
    Other Name: Temodal, Temomedac, CeCeNu
  • Drug: Temozolomide
    Other Name: Temodal, Temomedac
Study Arms  ICMJE
  • Experimental: lomustine (CCNU) + temozolomide (TMZ) and radiotherapy
    60 Gy standard radiotherapy (RT, 30 x 2 Gy) Six 42-day courses of oral CCNU 100 mg/m2 (day 1) and oral TMZ 100 mg/m2 (day 2-6), first CCNU application during the first week of RT CCNU/TMZ and radiotherapy start 2-5 weeks after diagnosis (day of surgery for glioblastoma (GBM)). In courses 2-6, TMZ dose are adjusted according to the hematotoxicity observed in the previous course and can be increased stepwise up to 200 mg/m2/day
    Intervention: Drug: Temozolomide and lomustine
  • Active Comparator: temozolomide and radiotherapy
    60 Gy standard radiotherapy (RT, 30 x 2 Gy) and concomitant TMZ therapy (daily TMZ 75 mg/m2) starting with the first day of radiotherapy Six 28-day courses of TMZ (day 1-5) starting 4 weeks after completion of radiotherapy. In the first course TMZ is given at a dose of 150 mg/m2/day, in case no toxicity is observed, the 2nd course is applied at a daily dose of 200 mg/m2
    Intervention: Drug: Temozolomide
Publications *

*   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: June 13, 2017)
141
Original Estimated Enrollment  ICMJE
 (submitted: June 22, 2010)
128
Actual Study Completion Date  ICMJE April 6, 2017
Actual Primary Completion Date April 6, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • written informed consent
  • patients have to be in a cognitive state that allows them to understand the rationale and necessity of study therapy and procedures.
  • newly diagnosed histologically proven GBM or gliosarcoma WHO Grad IV
  • methylated MGMT promoter in the tumor
  • estimated life expectancy of at least 12 weeks
  • Karnofsky Performance Score (KPS) ≥ 70%
  • patient compliance and geographic proximity that allow adequate follow up
  • male and female patients with reproductive potential must use an approved contraceptive method
  • pre-menopausal female patients with childbearing potential: a negative serum pregnancy test must be obtained prior to treatment start
  • Adequate organ function as described below:

Adequate bone marrow reserve:

white blood cell (WBC) count > 3000/µl, granulocyte count >1500/µl, platelets > 100000/µl, haemoglobin ≥ 10 g/dl Adequate liver function bilirubin < 1.5 times above upper limit of normal range (ULN), ALT and AST < 3 times ULN creatinine < 1.5 times ULN

Adequate blood clotting:

PT and PTT within normal limits Negative HIV test

Exclusion Criteria:

  • prior malignancy
  • prior chemotherapy
  • prior radiotherapy to the brain
  • concurrent administration of any other anti-tumor therapy
  • allergy or other intolerability of temozolomide, CCNU, dacarbazine or other nitrosourea derivatives
  • unable to undergo MRI
  • past medical history of diseases with poor prognosis
  • known HIV infection, active Hepatitis B or C infection
  • any active infection
  • female patients that are pregnant or breastfeeding
  • patients with reproductive potential who do not accept to use contraception
  • treatment in another clinical trial
  • any psychological, cognitive, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up scheduled visits (at the discretion of investigator)
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 NCT01149109
Other Study ID Numbers  ICMJE CeTeG
2009-011252-22 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ulrich Herrlinger, University Hospital, Bonn
Study Sponsor  ICMJE University Hospital, Bonn
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Ulrich Herrlinger, Prof. Dr. Division of Neurooncology, Departement of Neurology, University Hospital Bonn
PRS Account University Hospital, Bonn
Verification Date June 2017

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