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RECRUITINGPhase 2INTERVENTIONAL

ARISTOCRAT: Blinded Trial of Temozolomide +/- Cannabinoids

A Randomised Controlled Phase II Trial of Temozolomide With or Without Cannabinoids in Patients With Recurrent Glioblastoma

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

ARISTOCRAT is a phase II, multi-centre, double-blind, placebo-controlled, randomised trial to compare the cannabinoid Nabiximols with placebo in patients with recurrent MGMT methylated glioblastoma (GBM) treated with temozolomide (TMZ).

Who May Be Eligible (Plain English)

Who May Qualify: - Histological diagnosis of MGMT promoter methylated, IDH wild type (WT) GBM with consistent local molecular pathology (repeat biopsy at recurrence is NOT required). - First recurrence of GBM planned for systemic treatment as determined by local Multidisciplinary Team (MDT), including agreement of a Consultant Neuro-Radiologist that imaging changes are most in keeping with recurrence and not pseudo-progression. Patients with a prior recurrence treated by surgical resection alone are eligible at time of first recurrence planned for systemic treatment. - Patients must have received initial first-line treatment with standard dose conventionally fractionated radiotherapy (i.e. 40 Gy in 15 fractions or 54-60 Gy in 28-33 fractions; other regimes may be considered in consultation with the ARISTOCRAT Trial Office) with concomitant and adjuvant TMZ. - A minimum of 3 cycles of adjuvant TMZ must have been received. - A minimum of Stable Disease (SD) (or Partial Response (PR)/Complete Response (CR)) at the end of first-line treatment (measured by Response Assessment for Neuro-Oncology (RANO) criteria). - ≥3 months since day 28 of the last cycle of TMZ. - Karnofsky Performance Status ≥60. - Adequate hematologic, renal, and hepatic function within 14 days prior to randomisation: - Absolute neutrophil count (ANC) ≥1.5 x 109/L - Platelet count ≥100 x 109/L - Serum creatinine clearance (measured or calculated (using local standard practice)) \>30ml/min - Total serum bilirubin ≤1.5 x upper limit of normal (ULN) - Liver transaminases \<2.5 x ULN - If surgery has been performed for first recurrence, then the wound must be adequately healed and there must be residual enhancing disease on MRI within 21 days of surgery or new enhancement at later follow up deemed suitable for systemic treatment. - Recovered from previous treatment side-effects ≤ Grade 2. - If on systemic steroids, must be on stable (≥7 days) or decreasing dose of steroids. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: * Histological diagnosis of MGMT promoter methylated, IDH wild type (WT) GBM with consistent local molecular pathology (repeat biopsy at recurrence is NOT required). * First recurrence of GBM planned for systemic treatment as determined by local Multidisciplinary Team (MDT), including agreement of a Consultant Neuro-Radiologist that imaging changes are most in keeping with recurrence and not pseudo-progression. Patients with a prior recurrence treated by surgical resection alone are eligible at time of first recurrence planned for systemic treatment. * Patients must have received initial first-line treatment with standard dose conventionally fractionated radiotherapy (i.e. 40 Gy in 15 fractions or 54-60 Gy in 28-33 fractions; other regimes may be considered in consultation with the ARISTOCRAT Trial Office) with concomitant and adjuvant TMZ. * A minimum of 3 cycles of adjuvant TMZ must have been received. * A minimum of Stable Disease (SD) (or Partial Response (PR)/Complete Response (CR)) at the end of first-line treatment (measured by Response Assessment for Neuro-Oncology (RANO) criteria). * ≥3 months since day 28 of the last cycle of TMZ. * Karnofsky Performance Status ≥60. * Adequate hematologic, renal, and hepatic function within 14 days prior to randomisation: * Absolute neutrophil count (ANC) ≥1.5 x 109/L * Platelet count ≥100 x 109/L * Serum creatinine clearance (measured or calculated (using local standard practice)) \>30ml/min * Total serum bilirubin ≤1.5 x upper limit of normal (ULN) * Liver transaminases \<2.5 x ULN * If surgery has been performed for first recurrence, then the wound must be adequately healed and there must be residual enhancing disease on MRI within 21 days of surgery or new enhancement at later follow up deemed suitable for systemic treatment. * Recovered from previous treatment side-effects ≤ Grade 2. * If on systemic steroids, must be on stable (≥7 days) or decreasing dose of steroids. * Willing and able to provide trial-specific informed consent. * Willing and able to comply with trial requirements. * Age ≥16. * Able to start treatment within 28 days of randomisation. Exclusion Criteria: * Pathology inconsistent with IDH WT GBM (e.g. patients with molecular features of PXA or BRAF mutation will be excluded). * Prior invasive malignancy (except non-melanoma skin cancer), unless disease free for a minimum of one year. * Prior treatment with stereotactic radiotherapy, brachytherapy or Convection Enhanced Delivery (CED) of any agent. * Prior treatment, apart from debulking surgery, for first recurrence of GBM. * Any active co-morbidity making patient unsuitable for trial treatment in the view of the Investigator. * Personal history of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric diagnosis other than depression associated with their underlying glioma condition. * Prior allergic reaction or significant toxicity (≥Grade 3 CTCAE) related to TMZ treatment. * Current or recent cannabis or cannabinoid-based medications within 28 days of randomisation and/or unwilling to abstain for the duration of the trial. * Women who are pregnant, breastfeeding or a woman of childbearing potential who is unwilling to use effective contraceptive methods during trial treatment and for 6 months after completion of trial treatment. o Women of childbearing age must have a negative pregnancy test within 7 days prior to randomisation. * Men who are sexually active and unwilling/unable to use medically acceptable forms of contraception during trial treatment or for 6 months after completion of trial treatment. * Contra-indication to MRI or gadolinium. * Hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. * Known hypersensitivity to cannabinoids or excipients of the IMP. * Known history of current or prior alcohol or drug dependence. * Known Hepatitis B (HBV), Cytomegalovirus (CMV) or opportunistic infection. * Has received a live vaccine within 28 days prior to randomisation. * Unable to administer oromucosal medication due to mucosal lesions or other issues. * Participation in another therapeutic clinical trial whilst taking part in this trial. * Any psychological, familial, sociological or geographical condition hampering protocol compliance.

Treatments Being Tested

DRUG

Nabiximols

Oromucosal spray

DRUG

Temozolomide

Oral capsule

DRUG

Nabiximols-matched placebo

Nabiximols-matched placebo oromucosal spray

Locations (20)

Glan Clwyd Hospital
Bodelwyddan, Denbighshire, United Kingdom
Mount Vernon Hospital, The Hillingdon Hospitals NHS Foundation Trust
Northwood, Middlesex, United Kingdom
Aberdeen Royal Infirmary, NHS Grampian
Aberdeen, United Kingdom
Belfast City Hospital, Belfast Health and Social Care Trust
Belfast, United Kingdom
Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust
Birmingham, United Kingdom
Bristol Haematology & Oncology Centre, University Hospitals Bristol & Weston NHS Foundation Trust
Bristol, United Kingdom
Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust
Cambridge, United Kingdom
Velindre Cancer Centre, Velindre University NHS Trust
Cardiff, United Kingdom
Western General Hospital, NHS Lothian
Edinburgh, United Kingdom
Beatson West of Scotland Cancer Centre, NHS Greater Glasgow & Clyde
Glasgow, United Kingdom
Castle Hill Hospital, Hull University Teaching Hospitals NHS Trust
Hull, United Kingdom
St James's University Hospital, Leeds Teaching Hospitals NHS Trust
Leeds, United Kingdom
St Bartholomew's Hospital, Barts Health NHS Trust
London, United Kingdom
Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust
London, United Kingdom
Charing Cross Hospital, Imperial College Healthcare NHS Trust
London, United Kingdom
Maidstone Hospital, Maidstone and Tunbridge Wells NHS Trust
Maidstone, United Kingdom
The Christie Hospital, The Christie NHS Foundation Trust
Manchester, United Kingdom
Clatterbridge Cancer Centre, The Clatterbridge Cancer Centre NHS Foundation Trust
Metropolitan Borough of Wirral, United Kingdom
City Hospital, Nottingham University Hospitals NHS Trust
Nottingham, United Kingdom
Churchill Hospital, Oxford University Hospitals NHS Foundation Trust
Oxford, United Kingdom