Contact information
Type
Scientific
Primary contact
Dr Pierre Robe
ORCID ID
Contact details
University Hospital of Liege
University of Liege
Domaine du Sart Tilman B35
Liege
4000
Belgium
+32 (0)4 366 7209
pierre.robe@ulg.ac.be
Additional identifiers
EudraCT number
2004-004392-11
ClinicalTrials.gov number
Protocol/serial number
Ulg_GBM_04/1
Study information
Scientific title
Acronym
Study hypothesis
Recent evidence suggests that the transcription factor NF-kappaB is constitutively expressed in malignant gliomas and that its inhibition by drugs like sulfasalazine may block the growth of astrocytic tumours in vitro and in experimental models of malignant gliomas. The aim of this study is to evaluate the safety and efficacy of sulfasalazine as a treatment for progressive or recurring malignant gliomas.
Ethics approval
The protocol was reviewed and approved by the Ethics Committee of the Faculty of Medicine of the University of Liège (IRB file number 2004/185). It also underwent review and approval by Belgian Federal Authorities (authorisation reference 548/03/05) and was granted the European Trial database (EudraCT) number 2004-004392-11.
Study design
A phase I - II, single centre, prospective, randomised, double blind clinical study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Progressive malignant glioma (astrocytic)
Intervention
The randomisation of patients between groups is provided by the Department of Statistics of the Faculty of Medicine of the University of Liège and the drug dosage is communicated only to the hospital pharmacist who prepares and delivers the drug. In order to facilitate the interim analysis of the data by the review committee, the randomisation algorithm was weighted so that 8 of the first 10 patients receive either the lowest or the highest drug dosage. Neither the investigators nor the patients are aware of the drug dosage that they provide/receive.
Sulfasalazine will be given orally three times a day at total doses of 1.5, 3, 4.5 or 6 g. Four capsules of the drug are to be taken with each meal. Sulfasalazine is to be taken continuously until radiological evidence of tumour progression, complete remission, or the development of serious or intolerable adverse effects. The patient may at any moment decide to discontinue his participation to the study, although every effort will be made to be able to carry on the follow-up. Finally, the independent review committee may decide at any moment to end the study based on safety issues.
Intervention type
Drug
Phase
Phase I/II
Drug names
Sulfasalazine
Primary outcome measure
1. The maximal daily oral dose of sulfaslazine that is tolerated by patients with recurrent or progressive malignant gliomas. Measurements will include the nature, frequency, possible causality and severity of adverse events that occur during treatment
2. The assessment of any clinical and/or radiological response of individual tumours to sulfasalazine
Secondary outcome measures
Overall and progression free survival following the initiation of sulfasalazine treatment.
Overall trial start date
15/06/2005
Overall trial end date
15/06/2007
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Adult patients aged greater than 18 years
2. With recurrent or progressive World Health Organization (WHO) grade 3 or 4 astrocytic gliomas after surgery
3. Standard radiation therapy
4. A first line of conventional chemotherapy (e.g. temozolomide, CCNU or BCNU)
Recurrence or progression prior to inclusion are based on MacDonalds criteria. Patients are thoroughly informed about the nature of their disease, suspected prognosis, study background and objectives and potential alternative treatments. This information is provided both orally and in written form, prior to obtaining written informed consent from the patient.
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
20
Participant exclusion criteria
1. Present with anaplastic oligodendroglioma (WHO grade 3)
2. Allergy to sulfa drugs
3. Porphyria
4. G-6-PD deficiency
5. Psychiatric disorder deemed incompatible with compliance to the study
6. Creatinine greater than 15 mg/l
7. Aspartate aminotransferase (TGO) greater than 200 UI/l
8. Amylase greater than 150 UI/l
9. Pregnant or lactating women
10. Patients may not have received any other experimental medication within 30 days (and at least five drug half-lives) prior to inclusion
11. Patients cannot concomitantly take mercaptopurine
Recruitment start date
15/06/2005
Recruitment end date
15/06/2007
Locations
Countries of recruitment
Belgium
Trial participating centre
University Hospital of Liege
Liege
4000
Belgium
Funders
Funder type
Research organisation
Funder name
Leon Frederic Fund (Belgium)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
National Fund for Scientific Research (Belgium)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
1. 2006 Protocol in http://www.ncbi.nlm.nih.gov/pubmed/16448552
2. 2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19840379
Publication citations
-
Protocol
Robe PA, Martin D, Albert A, Deprez M, Chariot A, Bours V, A phase 1-2, prospective, double blind, randomized study of the safety and efficacy of Sulfasalazine for the treatment of progressing malignant gliomas: study protocol of [ISRCTN45828668]., BMC Cancer, 2006, 6, 29, doi: 10.1186/1471-2407-6-29.
-
Results
Robe PA, Martin DH, Nguyen-Khac MT, Artesi M, Deprez M, Albert A, Vanbelle S, Califice S, Bredel M, Bours V, Early termination of ISRCTN45828668, a phase 1/2 prospective, randomized study of sulfasalazine for the treatment of progressing malignant gliomas in adults., BMC Cancer, 2009, 9, 372, doi: 10.1186/1471-2407-9-372.