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)

NCT01602588 | Completed Phase 2 DMC

• 1 other identifier: UCL11/0404
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 15

Brief Summary

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.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Toxicity

  Toxicity will be assessed during and up to 30 days after treatment

Study Arms (2)

Arm B

EXPERIMENTAL

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

Arm A: SCRT alone

ACTIVE COMPARATOR

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

Radiation: Radiotherapy

Interventions

Hydroxychloroquine DRUG

200mg bd from 14 days post surgery until clinical or radiological progression

Also known as: HCQ

Arm B

Radiotherapy RADIATION

Short Course radiotherapy

Arm A: SCRT alone

Eligibility Criteria

• Age: 70 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University College, London: lead
• Cancer Research UK: collaborator

Study Sites (15)

St James's University Hospital

Leeds, West Yorkshire, LS9 7TF, United Kingdom

Location

Glan Clwyd Hospital

Bodelwyddan, LL18 5UJ, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Ninewells Hospital

Dundee, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Royal Surrey County Hospital

Guildford, GU2 7XX, United Kingdom

Location

University College Hospital

London, NW1 2BU, United Kingdom

Location

Guy's and St Thomas's Hospitals

London, SE1 9RT, United Kingdom

Location

Charing Cross Hospital

London, w6 8RF, United Kingdom

Location

Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

James Cook University Hospital

Middlesbrough, TS4 3BW, United Kingdom

Location

Freeman Hospital

Newcastle, NE7 7DN, United Kingdom

Location

Norfolk & Norwich University Hospitals

Norwich, NR4 7UY, United Kingdom

Location

The Royal Preston Hospital

Preston, PR2 9HT, United Kingdom

Location

Royal Stoke University Hospital

Stoke-on-Trent, ST4 6QG, United Kingdom

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Hydroxychloroquine; Radiotherapy

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Therapeutics

Study Officials

• Susan Short, Professor

  St James's University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2012
• First Posted: May 21, 2012
• Study Start: May 1, 2013
• Primary Completion: October 1, 2016
• Study Completion: November 1, 2017
• Last Updated: May 3, 2018

Record last verified: 2018-05

Locations

GB (15)