A Randomised Trial Investigating the Additional Benefit of Hydroxychloroquine(HCQ)to Short Course Radiotherapy (SCRT) in Patients Aged 70 Years and Older With High Grade Gliomas (HGG)

Study Overview
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Brief Summary
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There is emerging evidence that hydroxychloroquine (HCQ), a drug used commonly in the prevention/ treatment of malaria, rheumatoid arthritis and lupus erythematosus, may improve survival outcome in a variety of cancers including HGG, with few side effects. In this trial the investigators wish to investigate whether treatment with radiotherapy and hydroxychloroquine is more effective than treatment with radiotherapy alone.

Official Title
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A Randomised Phase 2 Trial Investigating the Additional Benefit of Hydroxychloroquine(HCQ)to Short Course Radiotherapy (SCRT) in Patients Aged 70 Years and Older With High Grade Gliomas (HGG)

Conditions
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Glioblastoma

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients aged ≥70 yrs identified through the neurooncology MDT. A histological diagnosis of HGG, either from biopsy or resection. A life expectancy of > 2 months An ECOG performance status of 0/1 Absolute neutrophil count ≥ 1.5 x 109 Platelet count ≥ 100 x 109 Bilirubin ≤ 1.5 mg/dL (or ≤ 25.6 µmol/L) Creatinine ≤ 2 times upper limit of normal (ULN) ALT and AST ≤ 4 times ULN Mini Mental Status Exam score ≥ 17 (Appendix 10) Written informed consent Ready to start radiotherapy within 4 weeks of surgery Exclusion Criteria: Concurrent psoriasis unless the disease is well controlled and patient is under the care of a specialist for the disorder who agrees to monitor for exacerbations Prior macular degeneration or diabetic retinopathy Concurrent serious infection or medical illness that would preclude study therapy Another malignancy within the past 5 years except for curatively treated carcinoma in situ or basal cell carcinoma of the skin Porphyria Glucose- 6 phosphate dehydrogenase (G6PD) deficiency Alcoholic liver disease Any other concurrent severe/uncontrolled medical conditions Currently taking amiodarone Prior radiotherapy, chemotherapy, immunotherapy, biologic agents (e.g., immunotoxins, immunoconjugates, antisense agents, peptide receptor antagonists, interferons, interleukins, tumour-infiltrating lymphocytes, lymphokine-activated killer cell therapy, or gene therapy), or hormonal therapy for brain tumour Prior polifeprosan 20 with carmustine implant (Gliadel wafer) or GliaSite® brachytherapy Concurrent cytochrome P450 enzyme-inducing anticonvulsant drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, or oxcarbazepine) Other concurrent chemotherapeutic or investigational agents for this cancer (Concurrent glucocorticoids will be allowed Documented side effects to chloroquine or related agents. Unable to give informed consent Patients with a history of a psychological illness or condition that in the opinion of the investigator may adversely affect compliance with study medication

Ages Eligible for Study
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Minimum Age: 70 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm B<br>Patients randomised to Arm B will receive Short Course Radiotherapy plus Hydroxychloroquine 200mg bd from 14 days post surgery until clinical or radiological progression. | Drug: Hydroxychloroquine<br>* 200mg bd from 14 days post surgery until clinical or radiological progression<br>* Other names: HCQ;|
| Active Comparator: Arm A: SCRT alone<br>Patients randomised to Arm A will receive standard treatment of Short Course Radiotherapy | Radiation: Radiotherapy<br>* Short Course radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1 year Survival | The primary endpoint of the trial is survival at one year | The survival rate will be calculated by the number of patients alive 1 year after entering the trial. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity | Adverse Events will be collected for all patients in the trial during treatment and up to 30 days afterwards. | Toxicity will be assessed during and up to 30 days after treatment |