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)

University College London (UCL)

Status and phase: Completed; Phase 2

Conditions: Glioblastoma

Treatments: Drug: Hydroxychloroquine; Radiation: Radiotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT01602588

UCL11/0404

Details and patient eligibility

About

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.

Enrollment: 54 patients

Sex: All

Ages: 70 to 100 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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54 participants in 2 patient groups

Arm B

Experimental group

Description:

Patients randomised to Arm B will receive Short Course Radiotherapy plus Hydroxychloroquine 200mg bd from 14 days post surgery until clinical or radiological progression.

Treatment:

Drug: Hydroxychloroquine

Arm A: SCRT alone

Active Comparator group

Description:

Patients randomised to Arm A will receive standard treatment of Short Course Radiotherapy

Treatment:

Radiation: Radiotherapy