NCT02432417

The Addition of Chloroquine to Chemoradiation for Glioblastoma,

Withdrawn Phase 2 Last updated 18 November 2023

What this trial tests

Phase 2 trial testing Chloroquine in Glioblastoma. Withdrawn.

Timeline

10 November 2023

Primary endpoint
10 November 2023

10 November 2023

Quick facts

Lead sponsor	Maastricht Radiation Oncology
Phase	Phase 2
Status	Withdrawn
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Start date	10 November 2023
Primary completion	10 November 2023
Estimated completion	10 November 2023

Drugs / interventions tested

• Chloroquine (CHLOROQUINE) — full drug profile →

Conditions studied

• Glioblastoma — all drugs for Glioblastoma →
• Astrocytoma, Grade IV — all drugs for Astrocytoma, Grade IV →

Sponsor

Maastricht Radiation Oncology — full company profile →

Who can join

Adults 18 to 70, any sex, with Glioblastoma or Astrocytoma, Grade IV. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Tumor biomarkers for diagnosis, prognosis and targeted therapy.
   Zhou Y, Tao L, Qiu J, Xu J, et al · · 2024 · cited 379× · PMID 38763973 · DOI 10.1038/s41392-024-01823-2
2. Autophagy in cancer: moving from understanding mechanism to improving therapy responses in patients.
   Mulcahy Levy JM, Thorburn A. · · 2020 · cited 332× · PMID 31836831 · DOI 10.1038/s41418-019-0474-7
3. Tumor-associated macrophages: potential therapeutic strategies and future prospects in cancer.
   Li C, Xu X, Wei S, Jiang P, et al · · 2021 · cited 259× · PMID 33504575 · DOI 10.1136/jitc-2020-001341
4. Therapeutic Targeting of Autophagy.
   Towers CG, Thorburn A. · · 2016 · cited 214× · PMID 28029600 · DOI 10.1016/j.ebiom.2016.10.034
5. Repurposing Drugs in Oncology (ReDO)-chloroquine and hydroxychloroquine as anti-cancer agents.
   Verbaanderd C, Maes H, Schaaf MB, Sukhatme VP, et al · · 2017 · cited 198× · PMID 29225688 · DOI 10.3332/ecancer.2017.781
6. Metal-based <i>NanoEnhancers</i> for Future Radiotherapy: Radiosensitizing and Synergistic Effects on Tumor Cells.
   Liu Y, Zhang P, Li F, Jin X, et al · · 2018 · cited 184× · PMID 29556359 · DOI 10.7150/thno.22172
7. Radiotherapy as a tool to elicit clinically actionable signalling pathways in cancer.
   Petroni G, Cantley LC, Santambrogio L, Formenti SC, et al · · 2022 · cited 154× · PMID 34819622 · DOI 10.1038/s41571-021-00579-w
8. Radioresistance in Glioblastoma and the Development of Radiosensitizers.
   Ali MY, Oliva CR, Noman ASM, Allen BG, et al · · 2020 · cited 128× · PMID 32899427 · DOI 10.3390/cancers12092511