A clinical trial adding Sativex (a cannabis-based medicine) to standard treatment, temozolomide, to find out if it is beneficial for patients whose glioblastoma brain tumour has returned after treatment
- Conditions
- Glioblastoma multiformeCancer
- Registration Number
- ISRCTN11460478
- Lead Sponsor
- niversity of Birmingham
- Brief Summary
2024 Protocol article in https://doi.org/10.1186/s12885-023-11792-4 (added 16/01/2024)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 234
Current inclusion criteria as of 31/08/2023:
1. Histological diagnosis of MGMT promoter methylated, IDH wild type (WT) glioblastoma multiforme (GBM) with consistent local molecular pathology (repeat biopsy at recurrence is NOT required)
2. 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 and patient is planned for systemic treatment. Patients with a prior recurrence treated by surgical resection alone are eligible at time of first recurrence planned for systemic treatment.
3. 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 temozolomide (TMZ)
3.1 Minimum of 3 cycles of adjuvant TMZ must have been received
3.2. Minimum of SD (or PR/CR) at the end of first-line treatment
4. =3 months since day 28 of the last cycle of TMZ
5. Karnofsky Performance Status =60
6. Adequate hematologic, renal, and hepatic function within 14 days prior to randomisation:
6.1. Absolute neutrophil count (ANC) =1.5 x 109/L
6.2. Platelet count =100 x 109/L
6.3. Serum creatinine clearance (measured or calculated (using local standard practice)) >30 ml/min
6.4. Total serum bilirubin =1.5 x upper limit of normal (ULN)
6.5. Liver transaminases <2.5 x ULN
7. 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
8. Recovered from previous treatment side-effects = Grade 2
9. If on systemic steroids, must be on stable (=7 days) or decreasing dose of steroids
10. Willing and able to provide trial-specific informed consent
11. Willing and able to comply with trial requirements
12. Aged 16 years old and over
13. Able to start treatment within 28 days of randomisation
Previous inclusion criteria:
1. Histological diagnosis of MGMT promoter methylated, IDH wild type (WT) glioblastoma multiforme (GBM) with consistent local molecular pathology (repeat biopsy at recurrence is NOT required)
2. 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 and patient is planned for systemic treatment. Patients with a prior recurrence treated by surgical resection alone are eligible at time of first recurrence planned for systemic treatment.
3. Patients must have received initial first-line treatment with standard dose conventionally fractionated radiotherapy (i.e. 54-60 Gy in 28-33 fractions) with concomitant and adjuvant temozolomide (TMZ) (STUPP regime)
3.1 Minimum of 3 cycles of adjuvant TMZ must have been received
3.2. Minimum of SD (or PR/CR) at the end of first-line treatment
4. =4 months since day 28 of the last cycle of TMZ
5. Karnofsky Performance Status =60
6. Adequate hematologic, renal, and hepatic function within 14 days prior to randomisation:
6.1. Absolute neutrophil count (ANC) =1.5 x 109/L
6.2. Platelet count =100 x 109/L
6.3. Serum creatinine clearance (measured or eG
Current exclusion criteria as of 08/11/2022:
1. Pathology inconsistent with IDH WT glioblastoma multiforme (GBM) (e.g. patients with molecular features of PXA or BRAF mutation (on original pathology) will be excluded)
2. Prior invasive malignancy (except non-melanoma skin cancer), unless disease free for a minimum of one year
3. Prior treatment with stereotactic radiotherapy, brachytherapy or Convection Enhanced Delivery (CED) of any agent
4. Prior treatment, apart from debulking surgery, for first recurrence of GBM
5. Any active co-morbidity making patient unsuitable for trial treatment in the view of the Investigator
6. Personal history of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric diagnosis other than depression associated with their underlying glioma condition
7. Prior allergic reaction or significant toxicity (=Grade 3 CTCAE) related to temozolomide treatment
8. Current or recent cannabis or cannabinoid-based medications within 30 days of randomisation and/or unwilling to abstain for the duration of the trial
9. 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
9.1. Women of childbearing age must have a negative pregnancy test within 7 days prior to randomisation
10. 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
11. Contra-indication to MRI or gadolinium
12. Hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption
13. Known hypersensitivity to cannabinoids or excipients of the IMP
14. Known history of current or prior alcohol or drug dependence
15. Known Hepatitis B (HBV), Cytomegalovirus (CMV) or opportunistic infection
16. Has received a live vaccine within 28 days prior to randomisation
17. Unable to administer oromucosal medication due to mucosal lesions or other issues
18. Participation in another therapeutic clinical trial whilst taking part in this trial
19. Any psychological, familial, sociological or geographical condition hampering protocol compliance
_____
Previous exclusion criteria:
1. Pathology inconsistent with IDH WT glioblastoma multiforme (GBM) (e.g. patients with molecular features of PXA or BRAF mutation (on original pathology) will be excluded)
2. Prior invasive malignancy (except non-melanoma skin cancer), unless disease free for a minimum of one year
3. Prior treatment with stereotactic radiotherapy, brachytherapy or Convection Enhanced Delivery (CED) of any agent
4. Prior treatment, apart from debulking surgery, for first recurrence of GBM
5. Any active co-morbidity making patient unsuitable for trial treatment in the view of the Investigator
6. Personal history of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric diagnosis other than depression associated with their underlying glioma condition
7. Prior allergic reaction or significant toxicity (=Grade 3 CTCAE) related to temozolomide treatment
8. Current or recent cannabis or cannabinoid-based medications within 30 days of randomisation and/or unwilling to abstain for the duration of the trial
9. Women who are pregnant, breastfeeding or a woman of childbearing potential who is unwilling to use effective contraceptive methods dur
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Overall survival time (OS), defined as the time in whole days from the date of randomisation to the date of death from any cause, measured using patient survival until the date of death. Patients who are alive at the time of analysis will be censored at the date last seen alive.
- Secondary Outcome Measures
Name Time Method 1. Overall survival measured using patient survival at 12 months (and 6 and 24 months)<br>2. Progression-free survival time, defined as the 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), 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<br>3. Health-related quality of life measured using the EORTC QLQ-C30, EORTC BN20, single items from the EORTC item library, and the EQ-5D-5L at screening and then every 8 weeks until the end of treatment<br>4. Adverse events measured using CTCAE v5.0 at 4-weekly intervals post-start of treatment up to progression or withdrawal