Phase III Trial of Primary Radio- or Chemotherapy in Malignant Astrocytoma of the Elderly
Phase III Trial of Primary Radio- or Chemotherapy in Malignant Astrocytoma of the Elderly
The study aims to optimize the treatment of elderly subjects (> 65) with anaplastic
 astrocytoma and glioblastoma. Current treatment policies tend to be no more than palliative.
 There is no consensus as to how radical the surgery should be. Involved-field radiotherapy is
 the treatment most likely to be accepted apart from supportive and palliative measures. The
 role of chemotherapy is barely defined. Study data available to date does not suggest that
 this patient population would benefit from combined radiochemotherapy. The aim of the study
 is to verify the hypothesis that first-line chemotherapy with one week on/one week off
 temozolomide is not inferior to extended-field radiotherapy in the first-line treatment of
 anaplastic astrocytoma and glioblastoma in the elderly (> 65 age group). The primary endpoint
 is median survival, as life expectancy is limited to several months. Secondary endpoints are
 response rates in both arms (CR, PR, MacDonald et al. 1990), median progression-free
 survival, 1-year and 2-year survival rates, definition of MGMT as molecular genetic
 prognostic or predictive markers, and quality of life. Theoretically, it should be possible
 to preserve quality of life in the first-line chemotherapy arm of the study.
This study is a prospective, randomized Phase III intervention study. Following histological
 documentation of the diagnosis by biopsy or resection of an anaplastic astrocytoma or
 glioblastoma, patients will be randomized either to receive postoperative extended-field
 radiotherapy (arm A) or to receive postoperative chemotherapy with temozolomide (arm B).
 Randomization will be done for all sites at the CRO, Alcedis GmbH.

 For patients intending to participate in the study, the procedure is as follows:

 -  Request a reference neuropathological review from the brain tumor reference center in
 Bonn (Prof. Dr. G. Reifenberger) through the local neuropathology department. This
 review need not be present at randomization because anaplastic astrocytoma and
 glioblastoma cases are eligible

 -  Contact: Prof. Dr. W. Wick, Dep. Neurooncology, National Center for Tumor Diseases and
 Neurology Clinic, University of Heidelberg, wolfgang.wick@med.uni-heidelberg.de or CRO:
 Alcedis, Giessen at Alcedis GmbH, I. Helm, Winchester Str. 2, 35394 Gießen, Tel.: 0641
 944360, Fax: 0641 94436 70, E-mail: ihe@alcedis.de

 -  Provide written confirmation that the patient signed the ethics committee-approved
 consent form

 -  Submit the registration form and a copy of the EORTC-QLQ given in Annexes

 In subjects with progressive or recurrent disease, the investigating site will verify whether
 specific tumor treatment is justified. If yes, chemotherapy with temozolomide is recommended
 in arm A, possibly after further surgery. Subjects in arm B will receive radiotherapy,
 possible after further surgery. As all-cause mortality is the primary endpoint, all
 therapeutic measures following first-line therapy should be documented.

 If study treatment is discontinued (first-line therapy) because of progressive disease or if
 progression occurs after completion of study treatment, the pertinent images should be
 submitted to the reference center for neuroradiology in Tübingen for reference review.

 The treatment modalities employed in the study are chemotherapeutic and radiotherapeutic
 procedures licensed in the Federal Republic of Germany for use in human subjects.
 Temozolomide is currently licensed for treating subjects with recurrent disease and since
 2006 in newly diagnosed glioblastoma together with radiotherapy. The time allotted for the
 individual treatment sections is 6 weeks for radiotherapy, while chemotherapy will be
 continued until progression or unacceptable adverse effects occur. The precise chemotherapy
 sequence is shown in the protocol. The criteria for withdrawal from the study are defined in
 in the protocol. Four years is the period scheduled for recruiting all patients.
Inclusion Criteria:

 -  Histologically confirmed supratentorial anaplastic astrocytoma or glioblastoma

 -  Age > 65

 -  Karnofsky performance score > 60%

 -  Neutrophilic granulocyte count > 1500/µl

 -  Platelet count > 100 000/µl

 -  Hemoglobin > 10 g/dl

 -  Serum creatinine < 1.5 times the lab's upper normal limit

 -  AST or ALT < 3 times the lab's upper normal limit

 -  Alkaline phosphatase < 3 times the lab's upper normal limit

 -  No previous systemic chemotherapy

 -  No previous radiotherapy to the brain

 -  Written consent

 Exclusion Criteria:

 -  Serious medical or neurological condition with a poor prognosis

 -  HIV infection

 -  Second cancer requiring radiotherapy or chemotherapy (contact the study coordinat if
 necessary)

 -  Hypersensitivity to temozolomide

 -  Conditions associated with regular vomiting that might affect oral administration of
 the drugs

 -  Psychological, familial, social or geographical circumstances with major implications
 for compliance with the study visit schedule

 -  Patient was taking part in other intervention studies within a month of starting this
 study