Glioblastoma, Optimizing Logistics and Dose (GOLD).

Standard radiotherapy (RT) treatment for patients with a glioblastoma
multiforme (GBM) is 30 times a 2 Gy fraction. This results in 30 visits to the
hospital in an overall treatment duration of six weeks. A significant reduction
of the number of fractions, i.e. extreme hypofractionation, has been proposed
and was successfully tested. However, due to the important EORTC trial in 2005,
where oral temozolomide chemotherapy was added to the standard of 30-fraction
radiotherapy, this regimen remained the standard of care for GBM patients. The
hypothesis of the GOLD study is that 6 fractions of high-precision,
hypofractionated radiotherapy delivered with a higher dose per fraction is
non-inferior to the standard fractionation schema and is associated with better
quality of life, and lowers the costs compared to standard treatment of GBM
patients.

To test whether extremely hypofractionated radiotherapy (6 x 6 Gy) is
non-inferior to standard radiotherapy (30 x 2 Gy) in terms of overall survival
in patients with newly diagnosed GBM. Secondary objectives are to establish
and compare health related quality of life (HRQoL), cost-effectiveness,
toxicity and progression-free survival in both treatment arms.

A phase III, open-label randomized controlled non-inferiority trial with 474
patients in two arms among all participating centers, which will be added in
amendments. The UMC Utrecht will expectedly include approximately 80 patients.

The investigational arm will be treated with hypofractionated radiotherapy 6
Gy, in 6 fractions per week, combined with daily temozolomide, followed by
adjuvant temozolomide. The control arm receives routine chemoradiotherapy with
fractionated radiotherapy in 30 sessions of 2 Gy (standard of care) combined
with daily temozolomide, followed by adjuvant temozolomide.

Participants will have to regularly visit the hospital to receive outpatient
treatment, with the number of visits dependent on allocation in the
investigational or control arm. After treatment, clinical follow-up will be
performed by their treating physicians, among which a radiation oncologist,
neuro-oncologist and internal oncologist. Additional follow-up will be
performed by self-administered questionnaires. Participants will be asked to
complete the HRQoL questionnaires EQ-5D-5L, EORTC QLQ-C30 and QLQ-BN20 at
baseline, 1 month after start of radiotherapy and every 3 months after start of
radiotherapy, and cost-utility questionnaires iMCQ and iPCQ at baseline and
every 3 months after start of radiotherapy. Furthermore, they will receive a
phone call every 3 months to be asked about adverse events and
anti-edema-treatment, as well as to be reminded to complete the questionnaires.
Finally, technical data, including MRI, CT and radiation treatment plans,
acquired in standard care will be utilized.