The Addition of Chloroquine to Chemoradiation for Glioblastoma
Status:
Completed
Trial end date:
2019-07-30
Target enrollment:
Participant gender:
Summary
Patients with a glioblastoma (GBM) have a poor prognosis with a median survival of 14.6
months after maximal treatment with a resection and chemoradiation. Since the pivotal trial
evaluating the effect of temozolomide (TMZ), overall survival has not increased.
Treatment of GBM xenografts in vivo with chloroquine (CQ), an antimalarial agent, has been
shown to reduce the hypoxic fraction and sensitizes tumors to radiation. Epidermal growth
factor receptor (EGFR) amplification or mutation is regularly observed GBM and is thought to
be a major contributor to radioresistance. The most common EGFR mutation in GBM (EGFRvIII) is
present in 50-60% of patients whose tumor shows amplification of EGFR. EGFR provides cells
with a survival advantage through autophagy when exposed to stresses such as hypoxia and
nutrient starvation. This effect is even more pronounced in EGFRvIII overexpressing tumors.
Previously, the potential effect CQ has been demonstrated in a small randomized controlled
trial in GBM treated with radiotherapy and carmustine, which showed a trend towards increased
overall survival. However, as the intracellular effects of chloroquine are dose-dependent the
maximum tolerated dose for CQ in combination with concurrent radiotherapy with daily
temozolomide needs to be established.