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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Ulrich Herrlinger, University Hospital, Bonn
ClinicalTrials.gov Identifier:
NCT01149109
First received: June 14, 2010
Last updated: June 3, 2015
Last verified: June 2015
  Purpose
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.

Condition Intervention Phase
Glioblastoma
Drug: Temozolomide and lomustine
Drug: Temozolomide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Trial of CCNU/Temozolomide (TMZ) Combination Therapy vs. Standard TMZ Therapy for Newly Diagnosed MGMT-methylated Glioblastoma Patients

Resource links provided by NLM:


Further study details as provided by University Hospital, Bonn:

Primary Outcome Measures:
  • overall survival [ Time Frame: after follow up (4 years) ]

Secondary Outcome Measures:
  • 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) ]

Estimated Enrollment: 128
Study Start Date: October 2010
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Temozolomide and lomustine
Other Name: Temodal, Temomedac, CeCeNu
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
Drug: Temozolomide
Other Name: Temodal, Temomedac

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01149109

Locations
Germany
Depatment of Neurosurgery, Charité, University Hospital Berlin
Berlin, Germany, 13353
Department of Neurology, University Hospital Bochum
Bochum, Germany, 44892
Department of Neurology, University Hospital Bonn
Bonn, Germany, 53105
Department of Neurosurgery, University Hospital Cologne
Cologne, Germany, 50937
Department of Neurosurgery, University Hospital Dresden
Dresden, Germany, 01307
Department of Neurosurgery, University Hospital Duesseldorf
Duesseldorf, Germany, 40225
Department of Neurosurgery, University Hospital Frankfurt
Frankfurt, Germany, 60528
Department of Radiooncology, University Hospital Leipzig
Leipzig, Germany, 04103
Department of Neurosurgery, University of Heidelberg, Medical Faculty of Mannheim
Mannheim, Germany, 68167
Department of Neurosurgery, University Hospital Muenster
Muenster, Germany, 48149
Department of Neurosurgery, University Hospital Munich (LMU)
Munich, Germany, 81377
Department of Neurology, University Hospital Regensburg
Regensburg, Germany, 93053
Sponsors and Collaborators
University Hospital, Bonn
Investigators
Study Director: Ulrich Herrlinger, Prof. Dr. Division of Neurooncology, Departement of Neurology, University Hospital Bonn
  More Information

Additional Information:
Responsible Party: Ulrich Herrlinger, Head, Division of Clinical Neurooncology, University Hospital, Bonn
ClinicalTrials.gov Identifier: NCT01149109     History of Changes
Other Study ID Numbers: CeTeG
2009-011252-22 ( EudraCT Number )
Study First Received: June 14, 2010
Last Updated: June 3, 2015

Keywords provided by University Hospital, Bonn:
MGMT promotor status
overall survival

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Lomustine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 24, 2017