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
EudraCT/CTIS number	2005-004622-24
ClinicalTrials.gov number	NCT00052455
Secondary identifying numbers	E164/47

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

http://cancerhelp.cancerresearchuk.org/trials/a-trial-looking-at-temozolomide-and-pcv-for-people-with-glioma-that-has-come-back-after-treatment

Study website

Contact information

Miss Sally Stenning
Scientific

MRC Clinical Trials Unit
222 Euston Road
London
NW1 2DA
United Kingdom

Email	br12@ctu.mrc.ac.uk

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Treatment
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
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Procarbazine, CCNU, vincristine, bis-chloronitrosourea, temozolomide
Primary outcome measure	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.
Secondary outcome measures	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.
Overall study start date	03/01/2003
Completion date	01/01/2008

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	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

England
United Kingdom

Study participating centre

MRC Clinical Trials Unit

London
NW1 2DA
United Kingdom

Sponsor information

Medical Research Council (MRC) (UK)
Research council

20 Park Crescent
London
W1B 1AL
United Kingdom

Phone	+44 (0)20 7636 5422
Email	clinical.trial@headoffice.mrc.ac.uk
Website	http://www.mrc.ac.uk

Funders

Funder type

Research council

Medical Research Council (UK)
Government organisation / National government

Alternative name(s): Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Plain English results				No	Yes
Results article	results	20/10/2010		Yes	No

Editorial Notes

05/10/2018: Cancer Research UK lay results summary link added to Results (plain English)