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The Addition of Chloroquine to Chemoradiation for Glioblastoma,

NCT02432417 · Status: WITHDRAWN · Phase: PHASE2 · Type: INTERVENTIONAL

Last updated 2023-11-18

No results posted yet for this study

Summary

Glioblastomas (GBM) are the most common type of primary brain tumors with an annual incidence of approximately 500 patients in the Netherlands. Despite extensive treatment including a resection, radiation therapy and chemotherapy, the median overall survival is only 14.6 months.

Epidermal growth factor receptor (EGFR) amplification or mutation is regularly observed in GBM and is thought to be a major contributor to resistance to radiotherapy and chemotherapy. The most common EGFR mutation in GBM (EGFRvIII) is present in 30-50% of GBM.

Previously MAASTRO lab has shown that expression of EGFRvIII provides GBM cells with a survival advantage when exposed to stress factors such as hypoxia and nutrient deprivation. These metabolic stress factors activate a lysosomal degradation pathway, known as autophagy. Inhibition of autophagy sensitizes cells to hypoxia, reduces the viable hypoxic fraction in tumors with \> 40% and subsequently sensitizes these tumors to irradiation.

Chloroquine (CQ) is a potent autophagy blocker and is the most widely investigated substance in this context. Previously, the effect of CQ has been demonstrated in a small randomized controlled trial in GBM treated with radiotherapy and carmustine. Although not statistically significantly different, the rate of death over time was approximately half as large in patients receiving CQ as in patients receiving placebo. The intracellular effects of CQ are dose-dependent. Therefore, the authors suggest an increase in daily dose of CQ may be necessary. Furthermore, the combination of CQ with TMZ may induce more damage to the neoplastic cells.

In the phase I part of this trial the recommended dose of CQ in combination with radiotherapy and temozolomide will be tested. In the phase II part of the trial patients with a histologically confirmed GBM will be randomized between standard treatment consisting of concurrent radiotherapy with temozolomide and adjuvant temozolomide (arm A) and standard treatment plus CQ (arm B).

Conditions

Interventions

DRUG

Chloroquine

CQ will start with one week before the start of radiotherapy and end on the last day of radiotherapy.

Sponsors & Collaborators

  • Maastricht Radiation Oncology

    lead OTHER

Principal Investigators

  • Philippe Lambin, prof. · Maastro Clinic, The Netherlands

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Max Age
70 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2023-11-10
Primary Completion
2023-11-10
Completion
2023-11-10

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02432417 on ClinicalTrials.gov