cropped color_logo_with_background.png

Avastin Plus Radiotherapy in Elderly Patients With Glioblastoma

Study Purpose

The purpose of this study is to explore the efficacy of bevacizumab combined with radiotherapy compared with radiotherapy alone in the treatment of newly diagnosed glioblastoma in the elderly. - Trial with medicinal product

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 65 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion criteria:

Diagnosis: newly diagnosed glioblastoma in elderly patients. 1. Signed informed consent. 2. Age > 65 years. 3. Newly diagnosed supratentorial glioblastoma. 4. Eligible for first infusion of bevacizumab > 28 and > 49 days after surgery for glioblastoma. 5. Karnofsky performance score 60 or more. 6. Paraffin-embedded tissue for central pathology review. 7. Stable or decreasing corticosteroid dose within 5 days prior to enrolment. 8. Adequate haematological function: 9. Adequate liver function. 10. Adequate renal function.

Exclusion criteria:

1. Karnofsky performance score 50 or less. 2. Evidence of recent hemorrhage on postoperative brain MRI. 3. Tumor with infiltration of retina, optic nerve, optic chiasm or brainstem. 4. Any prior chemotherapy including carmustine-containing wafers (GliadelĀ®) or immunotherapy for glioblastoma or lower grade astrocytomas. 5. Any prior radiotherapy to the brain or prior radiotherapy resulting in a potential overlap in the radiation field. 6. Inadequately controlled hypertension. 7. History of hypertensive crisis or hypertensive encephalopathy. 8. New York Heart Association (NYHA) grade II or higher congestive heart failure. 9. Myocardial infarction or unstable angina within 6 months prior to enrolment. 10. Stroke or transitory ischemic attack within 6 months prior to enrolment. 11. Other significant vascular disease within 6 months prior to enrolment. 12. History of = grade 2 haemoptysis within 1 month prior to enrolment. 13. Bleeding diathesis or coagulopathy in the absence of therapeutic anticoagulation. 14. Major surgical procedure, open biopsy, intracranial biopsy, ventriculoperitoneal shunt or significant traumatic injury within 28 days prior to first dose of bevacizumab. 15. Core biopsy (excluding intracranial biopsy) or other minor surgical procedure within 7 days prior to first dose of bevacizumab. 16. Abdominal fistula or gastrointestinal perforation within 6 months prior to enrolment. 17. Intracranial abscess within 6 months prior to enrolment. 18. Serious non-healing wound, active ulcer or untreated bone fracture. 19. Pregnancy or lactation. 20. Fertile women < 2 years after last menstruation and men unwilling or unable to use effective means of contraception. 21. Active malignancy that may interfere with the study treatment at the investigator?s and PI discretion

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT01443676
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Zurich
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

01 Studienregister MasterAdminsMichael Weller, Professor
Principal Investigator Affiliation UniversitaetsSpital ZuerichUniversity Hospital Zurich, Division of Neurology
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Completed
Countries Switzerland
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Glioblastoma
Additional Details

This is a randomized (2:1), explorative, parallel-group, open-label, phase II trial in elderly patients with newly diagnosed glioblastoma. In the control arm, patients will receive radiotherapy, in the experimental arm, patients will receive bevacizumab during and after radiotherapy until progression. Background: For decades, neurosurgical resection and postoperative radiotherapy have been the cornerstones of treatment for patients with glioblastoma. Most chemotherapeutic agents showed little or no activity in malignant glioma patients, with the possible exception of nitrosoureas. This has changed with the introduction of temozolomide, first shown to be active in recurrent disease (Yung et al. 2000) and more recently in newly diagnosed glioblastoma (Stupp et al. 2005, 2009). This EORTC 26981-22981 NCIC CE.3 trial demonstrated an increase in median survival from 12.1 to 14.6 months and of the 2 year survival rate from 10% to 26% in patients receiving radiotherapy plus temozolomide compared with radiotherapy alone. Notably patients with tumors exhibiting methylation of the promoter region of the O6-methylguanine DNA methyltransferase (MGMT) gene showed a striking benefit from temozolomide (Hegi et al. 2005). Yet, inclusion in this trial was limited to patients up to the age of 70, and subgroup analyses demonstrated that younger patients were more likely to derive benefit from combined modality treatment than older patients. Thus, radiotherapy alone is still the standard of care in the elderly. The value of radiotherapy has been confirmed in a small randomized trial comparing best supportive care versus radiotherapy alone: median survival was 29 weeks with radiotherapy compared with 16.9 weeks with supportive care only (Keime-Guibert et al. 2007). Based on the overall shorter survival in elderly patients, hypofractionated radiotherapy has been explored and shown to be equieffective in patients aged 65-70 years and more (Roa et al. 2004). Two randomized trials presented in abstract form at the Annual Meeting of the American Society of Clinical Oncology in June 2010 failed to show superiority of primary temozolomide chemotherapy alone over radiotherapy alone in elderly patients (Malmstrom et al. 2010, Wick et al. 2010a). In fact, the German NOA-08 trial even showed that primary temozolomide alone is not non-inferior to primary radiotherapy alone (Wick et al. 2010a). A concomitant treatment strategy is currently evaluated in a NCIC-EORTC randomized trial. Further, the Nordic trial corroborated the equieffectiveness of an accelerated radiotherapy protocol of 40 Gy administered in 15 fractions versus the standard fractionation of 30 x 2 Gy. Altogether, these clinical data justify the exploration of new, temozolomide-free first-line treatment strategies in glioblastoma. Glioblastomas express high levels of vascular endothelial growth factor (VEGF) and are highly vascularized tumors. The VEGF antibody, bevacizumab, has recently gained approval in patients with recurrent glioblastoma in the USA and in Switzerland in 2009, but not in the EU. Its role in the first-line treatment of glioblastoma is currently being evaluated in randomized trials. There is limited data on the safety and efficacy of bevacizumab in elderly patients with glioblastoma, although the safety profile of bevacizumab in elderly patients with other types of cancer, e.g., lung cancer is favorable. There are ample rationales for combining bevacizumab with radiotherapy, including the induction of VEGF by radiotherapy and the concept of vascular normalization resulting in increased oxygenation and thus sensitivity to radiotherapy. Thus, bevacizumab is not only expected to inhibit angiogenesis, but may also exhibit additive or synergistic interactions with radiotherapy and further impair tumor growth. Altogether, this study seeks to explore, using a dedicated neuroimaging protocol, the possibility that bevacizumab enhances the effects of radiotherapy via the process of vascular normalization. The purpose of this study is to explore the efficacy of bevacizumab combined with radiotherapy compared with radiotherapy alone in the treatment of newly diagnosed glioblastoma in the elderly.

Arms & Interventions

Arms

Active Comparator: Radiotherapy

Radiotherapy

Experimental: Radiotherapy plus Bevacizumab

Radiotherapy plus Bevacizumab

Interventions

Drug: - Bevacizumab

Bevacizumab will be added to radiotherapy

Radiation: - Radiation therapy

Radiation therapy

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Zurich, Switzerland

Status

Address

Department of Neurology, University Hospital Zurich

Zurich, ,