A phase I trial for the addition of chloroquine, an autophagy inhibitor, to concurrent chemoradiation for newly diagnosed glioblastoma
- Conditions
- astrocytoma grade IVGlioblastomamalignant braintumour10029211
- Registration Number
- NL-OMON44953
- Lead Sponsor
- MAASTRO clinic
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 13
• Histologically confirmed grade IV supratentorial astrocytoma (glioblastoma multiforme)
• Tumor tissue available for histopathological analysis (MGMT, EGFRvIII)
• Diagnosis must have been made by biopsy or resection <= 6 weeks prior to study entry
• 18 - 70 years
• Karnofsky performance status >=70
• Absolute neutrophil count at least 1.5 x 109/L and platelets at least 100 x109/L
• Adequate renal function: serum creatinine <= 1.5 x upper limit of normal (UNL)
• Adequate hepatic function: total bilirubin <= 1.5 x UNL for the instituion; ALT, AST, and alkaline phosphatase <= 3 x UNL for the institution
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
• Willingness to use contraception by a method that is deemed effective by the Investigator throughout the treatment period and for at least 30 days following the last dose of therapy
• If female, postmenopausal for at least 2 years, surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or practicing an appropriate method of birth control
• If male, subject must be surgically sterile or practicing an appropriate method of contraception and refrain from sperm donation, from initial drug administration until 90 days after the last dose of study drug:
• Ability to swallow and take oral medication.
• Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations
• Prior radiotherapy
• Prior chemotherapy
• Recent (< 3 months) severe cardiac disease (NYHA class >1) (congestive heart failure, infarction)
• History of cardiac arrythmia which is symptomatic and requiring treatment, or asymptomatic sustained ventricular tachycardia. Asymptomatic atrial fibrillation controlled on medication is allowed.
• Cardiac conduction disturbances or medication potentially causing them
• Treatment with investigational drugs in 4 weeks prior to or during this study
• If the subject has clinically significant and uncontrolled major medical condition(s) including but not limited to uncontrolled nausea/vomiting/diarrhea; active uncontrolled infection; psychiatric illness/social situation that would limit compliance with study requirements; any medical condition, with the opinion of the study investigator, places the subject at an unacceptably high risk for toxicities
• Another active malignancy within the past 3 years except for any cancer in situ that the principal investigator considers to be cured
• Chronic systemic immune therapy (with the exception of corticosteroids)
• Concurrent cytochrome P450 enzyme-inducing anticonvulsant drugs
• Known Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Psoriasis or porphyria
• Known hypersensitivity to 4-aminoquinoline compound
• Retinal or visual field changes unrelated to the tumor location prior to 4-aminoquinoline compound use
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>• Incidence of dose-limiting toxicities. </p><br>
- Secondary Outcome Measures
Name Time Method <p>• Adverse Events (AEs), serious AEs (SAEs), changes in haematology and<br /><br>chemistry values, electrocardiograms, tone audiograms or ophthalmologic<br /><br>examination.<br /><br>• Pharmacokinetics of CQ<br /><br>• Presence of autophagic marker (LC3b)<br /><br>• Gene mutation, deletion or amplification such as MGMT, EGFRvIII in tumor<br /><br>tissue pre-treatment<br /><br>• Radiological response on follow-up MRI<br /><br>• Time from inclusion until death from any cause<br /><br>• Time from inclusion until disease progression or death</p><br>