A prospective randomised trial comparing temozolomide with standard nitrosourea-based chemotherapy (PCV [procarbazine, CCNU, vincristine]/BCNU [bis-chloronitrosourea]) in the treatment of recurrent WHO astrocytic tumours grades III and IV (anaplastic astrocytoma and glioblastoma multiforme)
| ISRCTN | ISRCTN83176944 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN83176944 |
| ClinicalTrials.gov (NCT) | NCT00052455 |
| Clinical Trials Information System (CTIS) | 2005-004622-24 |
| Protocol serial number | E164/47 |
| Sponsor | Medical Research Council (MRC) (UK) |
| Funder | Medical Research Council (UK) |
- Submission date
- 21/09/2000
- Registration date
- 21/09/2000
- Last edited
- 05/10/2018
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Contact information
Miss Sally Stenning
Scientific
Scientific
MRC Clinical Trials Unit
222 Euston Road
London
NW1 2DA
United Kingdom
| br12@ctu.mrc.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomised controlled trial |
| Secondary study design | Randomised controlled trial |
| Scientific title | A prospective randomised trial comparing temozolomide with standard nitrosourea-based chemotherapy (PCV [procarbazine, CCNU, vincristine]/BCNU [bis-chloronitrosourea]) in the treatment of recurrent WHO astrocytic tumours grades III and IV (anaplastic astrocytoma and glioblastoma multiforme) |
| Study acronym | BR12 |
| Study objectives | BR12 is a randomised trial which compares standard PCV chemotherapy with two temozolomide schedules in patients with histologically confirmed recurrent World Health Organisation (WHO) Grade III or IV astrocytic tumour who have had primary radiotherapy (but no prior chemotherapy). More details can be found at: http://www.ctu.mrc.ac.uk/research_areas/study_details.aspx?s=7 |
| Ethics approval(s) | No ethics information required at time of registration. |
| Health condition(s) or problem(s) studied | Astrocytic tumours (anaplastic astrocytoma and glioblastoma multiforme) |
| Intervention | 1. Temozolomide according to one of two schedules: a. Temozolomide, 200 mg/m^2 orally (po) days one to five b. Temozolomide, 100 mg/m^2 po days one to 21 2. PCV chemotherapy (CCNU 100 mg/m^2 po day one, Procarbazine 100 mg/m^2 po days one to ten, Vincristine 1.5 mg/m^2 (max 2 mg) intravenous (iv) day one) |
| Intervention type | Drug |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Procarbazine, CCNU, vincristine, bis-chloronitrosourea, temozolomide |
| Primary outcome measure(s) |
The primary objective of the trial is to evaluate, in a group of patients representative of those who are considered for chemotherapy outside of trials, the potential benefit of temozolomide compared to PCV with respect to survival in patients with recurrent malignant glioma. |
| Key secondary outcome measure(s) |
In addition, the treatments will be compared with respect to the following secondary outcome measures: survival free from progression (confirmed radiologically), and health-related quality of life. A further objective is to evaluate the comparative efficacy (progression-free survival) and toxicity of the two different temozolomide schedules. |
| Completion date | 01/01/2008 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | All |
| Target sample size at registration | 500 |
| Key inclusion criteria | 1. Patients with histologically verified anaplastic astrocytoma, glioblastoma multiforme or gliosarcoma (WHO grade III/IV at diagnosis or relapse) who have undergone primary treatment which must include radiotherapy 2. Evidence of first progression confirmed by imaging (Computed Tomography [CT] or Magnetic Resonance Imaging [MRI]) 3. Evaluable enhancing recurrent tumour on contrast enhanced MRI/CT scan (within 14 days prior to start of treatment) 4. Life expectancy more than or equal to one month (based on age, performance status) 5. Considered fit for chemotherapy 6. More than or equal to two months from completion of radiotherapy 7. No previous chemotherapy, radiosurgery or interstitial radiotherapy (brachytherapy) for glioma; debulking surgery on relapse is permissible 8. Adequate hepatic, renal and haematological function (within 14 days prior to entry). Absolute Neutrophil Count (ANC) more than or equal to 1500/mm^3; platelet count more than or equal to 100,000/mm^3; Blood Urea Nitrogen (BUN) and serum creatinine less than 1.5 x Upper Limit of local laboratory Normal range (ULN); Total and direct serum bilirubin less than 1.5 x ULN; Serum Glutamic-Oxaloacetic Transaminase (SGOT) or Serum Glutamic Pyruvic Transaminase (SGPT) less than 3 x ULN; Alkaline phosphatase less than 2 x ULN 9. Written informed consent given |
| Key exclusion criteria | Age less than 18 years WHO performance status grade 4 Previous recurrence Pregnancy, breast feeding, patient or partner not using adequate contraception Concomitant serious illness Patients diagnosed with Oligodendroglioma |
| Date of first enrolment | 03/01/2003 |
| Date of final enrolment | 01/01/2008 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
MRC Clinical Trials Unit
London
NW1 2DA
United Kingdom
NW1 2DA
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 20/10/2010 | Yes | No | |
| Plain English results | No | Yes | |||
| Study website | Study website | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
05/10/2018: Cancer Research UK lay results summary link added to Results (plain English)
