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The Addition of Chloroquine to Chemoradiation for Glioblastoma

NCT02378532 · Status: COMPLETED · Phase: PHASE1 · Type: INTERVENTIONAL · Enrollment: 13

Last updated 2020-01-23

No results posted yet for this study

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.

Conditions

Interventions

DRUG

Chloroquine

Three cohorts of 3 patients will receive chloroquine in escalating doses (3 dose levels: 200 mg up to 600 mg daily) during standard treatment (radiotherapy and temozolomide) for newly diagnosed GBM. Extra patients can be added to a cohort in case of dose limiting toxicity, resulting in a maximum of 6 patients per dose level. Based on the results of the DSMB an additional leven of 300mg was added.

RADIATION

Radiotherapy

Patients will receive megavoltage radiotherapy in a conventionally fractionated regimen of 59.4 Gy in 33 fractions in 6.5 weeks, using modern computer-based treatment planning and delivery techniques. Treatment should start within 6 weeks of surgery.

DRUG

Temozolomide

Patients will take TMZ 75 mg/m² po qd during the course of radiotherapy six adjuvant cycles of TMZ. After a 4 week break, patients will receive up to six cycles of adjuvant oral TMZ 150 - 200 mg/m² po qd for 5 days every 28 days. The starting dose is 150 mg/m² po qd. At the start of cycle 2 the dose will be escalated to 200mg/m2, if the CTC non-hematologic toxicity for cycle 1 is grade ≤2 (except for alopecia, nausea, and vomiting), absolute neutrophil count is ≥1.5 x 109/L and the platelet count ≥ 100 x 109/L.

Sponsors & Collaborators

  • Maastricht Radiation Oncology

    lead OTHER

Principal Investigators

  • Dirk De Ruysscher, prof. · Maastro Clinic, The Netherlands

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2016-08-31
Primary Completion
2019-01-17
Completion
2019-07-30

Countries

  • Netherlands

Study Locations

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Entities

Drugs
Diseases

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 NCT02378532 on ClinicalTrials.gov