A Safety Study of Sativex Compared With Placebo (Both With Dose-intense Temozolomide) in Recurrent Glioblastoma Patients

Prior treatment

• Patients currently receiving treatment for recurrent Glioblastoma Multiforme.
• Less than a four week interval since prior chemotherapy.
• Less than a 12 week interval since prior radiotherapy unless there is either: a) histopathology confirmation of recurrent tumour, or b) new enhancement on Magnetic Resonance Imaging outside of the radiotherapy treatment field.
• Any surgery, including intracranial biopsy (not including minor diagnostic procedures such as lymph node biopsy) within two weeks of baseline disease assessments; or not fully recovered from any side effects of previous procedures.
• Have previously received first line chemotherapy other than Temozolomide.
• Have previously received stereotactic radiotherapy, convection enhanced delivery or brachytherapy (as gliosis/scarring from these modalities may limit delivery).
• The patient is currently using or has used cannabis or cannabinoid based medications within 30 days of study entry and is unwilling to abstain for the duration of the study.
• Patient who have received an Investigational Medicinal Product within the four weeks prior to the screening visit.
• Patients previously enrolled into this study and received either Investigational Medicinal Product or Dose-Intense Temozolomide.

Other illness

• Presence of extra-cranial metastatic disease.
• Any history of a different malignancy unless the patient has remained disease-free for at least three years and are at low risk for recurrence of that malignancy (cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin are exempt from this criterion if treatment has occurred).
• Any known or suspected history of a substance abuse/dependence disorder, current heavy alcohol consumption (>60g of pure alcohol per day for men, >40 g of pure alcohol per day for women), current use of an illicit drug or current non prescribed use of any prescription drug.
• Any history or immediate family history of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
• Has experienced myocardial infarction or clinically significant dysfunction within the last 12 months or has a cardiac disorder that, in the opinion of the investigator would put the patient at risk of clinically significant arrhythmia or myocardial infarction.
• Any other significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, or may influence the result of the study, or the patient's ability to participate in the study.
• Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the Investigational Medicinal Product.
• Any known allergy to or other intolerability to Temozolomide.

Other

• Patients with Glioblastoma Multiforme secondary to low-grade glioma or anaplastic glioma (anaplastic astrocytoma or anaplastic oligodendroglioma).
• Presents with Leptomeningeal dissemination.
• Has grade 3 or above toxicity by Common Terminology Criteria for Adverse Events criteria.
• Female patients of child bearing potential and male patients whose partner is of child bearing potential, unless willing to ensure that they or their partner use effective contraception, for example, oral contraception, double barrier, intra-uterine device, during the study and for three months thereafter (however a male condom should not be used in conjunction with a female condom).
• Female patients who are pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter.
• Travel outside the country of residence planned during the study.
• Following a physical examination, the patient has any abnormalities that, in the opinion of the investigator would prevent the patient from safe participation in the study.
• Unwilling to abstain from donation of blood during the study.

• Patient is willing and able to give informed consent for participation in the study.
• Patient is aged 18 years or above.
• Histopathologically confirmed diagnosis of grade four Glioblastoma Multiforme as per World Health Organisation classification.
• Evidence of patients first tumour progression (as determined by Revised Assessment in Neuro-Oncology) following radiation and first line chemotherapy with Temozolomide.
• If taking steroids, then the dose must be stable or decreasing.
• Karnofsky performance scale of 60% or greater.
• Patient is able (in the investigators opinion) and willing to comply with all study requirements.
• Patient is willing for his or her name to be notified to the responsible authorities for participation in this study, as applicable in individual countries.
• Patient is willing to allow his or her primary care practitioner and consultant, if appropriate, to be notified of participation in the study.