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ARISTOCRAT: Blinded Trial of Temozolomide +/- Cannabinoids

ConditionsGlioblastomaBrain TumorCannabisBrain Tumor, Recurrent
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age16+
SponsorUniversity of Birmingham

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Nabiximols

    Drug

    Oromucosal spray

  • Temozolomide

    Drug

    Oral capsule

  • Nabiximols-matched placebo

    Drug

    Nabiximols-matched placebo oromucosal spray

Treatment groups

120 Participants
are divided into 2 treatment groups
Group A: Standard Temozolomide with NabiximolsExperimental treatment 2 interventions
Group B: Standard Temozolomide with Nabiximols-matched placeboPlacebo comparator 2 interventions

Trial outcomes

Primary outcomes

1

Overall survival time (OS)

To establish whether the addition of cannabinoids (Nabiximols) to standard TMZ treatment improves overall survival time (OS) in MGMT methylated recurrent GBM compared to the addition of placebo to TMZ.

Time frame
Time in whole days from date of randomisation to the date of death from any cause, assessed at a minimum of 12 months..

Secondary outcomes

1

Overall survival at 12 months (OS12) (and 6 and 24 months)

Of particular clinical relevance is the overall survival at 12 months from date of randomisation, i.e. whether the participant is alive or not at that time point. Overall survival at 6 months and 24 months will also be of interest.

Time frame
6, 12 and 24 months
2

Progression-free survival time (PFS)

Measured using Response Assessment for Neuro-Oncology (RANO) criteria at screening, weeks 10, 22, 30 then 3 monthly (as per standard of care) for up to a minimum of 52 weeks from the start of trial treatment. PFS includes radiological progression assessed in accordance with RANO criteria and clinical progression where radiological progression is not possible.

Time frame
Time in whole days from the date of randomisation to the date of the first documented evidence of disease progression or death (from any cause), whichever came first, assessed at a minimum of 12 months.
3

Health-related quality of life (HRQoL) as assessed by EORTC QLQ-C30

Generic Health-related quality of life (HRQoL) will be assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) consisting of function, symptom and global health status scales, scored 1-4 with lower scores indicating better outcomes..

Time frame
Baseline (Week 0), Week 8, Week 16, End of Treatment (Week 24)
4

Adverse events

Assessment of AEs according to the current NCI-CTCAE v5.0 criteria. Acute AE will be defined as those occurring up to 12 weeks post-end of treatment. Late AE will be defined as those occurring after 12 weeks post-end of treatment. The end of treatment will be the date of the final chemotherapy cycle.

Time frame
Baseline (Week 0), Week 4, Week 8, Week 12, Week 16, Week 20, End of Treatment (Week 24)

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Birmingham

Lead sponsor

University of Leeds

Collaborator

The Brain Tumour Charity

Collaborator

Jazz Pharmaceuticals

Collaborator

Source ClinicalTrials.gov
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