The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12618000922279
Ethics application status
Approved
Date submitted
17/03/2018
Date registered
31/05/2018
Date last updated
31/05/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Tocilizumab for the treatment of retroperitoneal fibrosis
Scientific title
Tocilizumab treatment for induction of remission in patients with idiopathic retroperitoneal fibrosis (TOCIRET)
Secondary ID [1] 294373 0
EUDRACT No. 2017-001429-41
Universal Trial Number (UTN)
Trial acronym
TOCIRET
Linked study record

Health condition
Health condition(s) or problem(s) studied:
retroperitoneal fibrosis 307106 0
Condition category
Condition code
Inflammatory and Immune System 306214 306214 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment with the monoclonal antibody Tocilizumab, given intravenously at a dose of 8 mk/kg every month for 6 consecutive months. This therapeutic regimen will apply to all enrolled patients. The drug will be administered in a hospital setting (day hospital), which will allow evaluation of patient's adherence.
Intervention code [1] 300677 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 305230 0
Remission is a composite endpoint, defined as absence of disease-related symptoms and hydronephrosis, in the presence of normal acute-phase reactants, and a prednisone dose max 5 mg/day.
This outcome will be assessed on the basis of: i) patient-reported symptoms; 2)measurement of acute-phase reactants (Erythrocyte sedimentation rate and C-reactive protein level); 3)imaging evaluation of hydronephrosis, assessed by ultrasound, computed tomography or magnetic resonance.
Timepoint [1] 305230 0
6 months (end of treatment)
Secondary outcome [1] 344543 0
Percentage of patients in remission. This will be assessed on the basis of patient reported symptoms and medical records reporting the results of laboratory tests (Erythrocyte sedimentation rate and C reactive protein) and imaging studies (ultrasound of the kidney and urinary tract, abdominal computed tomography or magnetic resonance)
Timepoint [1] 344543 0
Month 12 (6 months after the end of treatment)
Secondary outcome [2] 344544 0
Change in retroperitoneal fibrosis thickness (assessed by CT or MRI)
Timepoint [2] 344544 0
Months 6 and 12 after the start of treatment
Secondary outcome [3] 347507 0
Change in FDG uptake (assessed by PET) versus baseline
Timepoint [3] 347507 0
Months 6 and 12 after the start of treatment
Secondary outcome [4] 347528 0
Treatment-related toxicity (frequency, type and severity of adverse events)
Timepoint [4] 347528 0
This will be monitored monthly during treatment (months 1,2,3,4,5,6 after the start of treatment) and bi-monthly during the post-treatment follow-up (months 8, 10, 12 after the start of treatment)

Eligibility
Key inclusion criteria
- Clinically active idiopathic retroperitoneal fibrosis
- Absence of potential causes of retroperitoneal fibrosis
- Written informed consent
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Secondary forms of retroperitoneal fibrosis (infectious, neoplastic, post-radiation therapy, drug-related)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Not applicable
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
None
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Data will be presented as median (range) or mean (SD), where appropriate.
Survival will be analyzed using the Kaplan-Meier method
Paired t-tests or the corresponding non-parametric tests will be used to analyze changes in measurable parameters such as mass thickness, FDG uptake, ESR or CRP levels. P values <0.05 will be considered statistically significant.
All patients will be analyzed following an intention-to-treat analysis provided that they received at least 2 months of therapy


Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 10226 0
Italy
State/province [1] 10226 0
Parma, Firenze, Reggio Emilia

Funding & Sponsors
Funding source category [1] 299014 0
Commercial sector/Industry
Name [1] 299014 0
Roche
Address [1] 299014 0
Viale Gian Battista Stucchi, 110, 20900 Monza
Country [1] 299014 0
Italy
Primary sponsor type
Hospital
Name
Azienda Ospedaliero Universitaria di Parma
Address
Via Gramsci 14, 43126 Parma
Country
Italy
Secondary sponsor category [1] 298240 0
None
Name [1] 298240 0
None
Address [1] 298240 0
None
Country [1] 298240 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299952 0
Comitato Etico per Parma
Ethics committee address [1] 299952 0
Via Gramsci 14, 43126 Parma
Ethics committee country [1] 299952 0
Italy
Date submitted for ethics approval [1] 299952 0
18/12/2017
Approval date [1] 299952 0
22/12/2017
Ethics approval number [1] 299952 0
Protocol number 46706

Summary
Brief summary
In this prospective, open-label trial we will analyse the efficacy and safety of TCZ in a series of 18 patients with IRF who either experienced frequent relapses under adequate immunosuppressive therapy or had a clearly refractory disease and/or contraindications to glucocorticoid therapy.
Patients will receive a monthly TCZ dose of 8 mg/kg for six months. a follow-up period of at least an additional 6 months will follow.
The assessment of treatment efficacy will be evaluated as the rate of remission at months 6 and 12. Remission will be defined as absence of disease-related symptoms (abdominal or lumbar pain, testicular pain, constipation, systemic symptoms), resolution or improvement of hydronephrosis (without indwelling stents), near-normalization (i.e. normalization or reduction to <30% of basal values) of erythrocyte sedimentation rate and C-reactive protein levels, as previously described; remission will require a dose of prednisone equal to or lower than 5 mg/day.
Secondary outcomes will include the assessment of the percentage of reduction in IRF thickness at CT or MRI scans and the reduction of FDG uptake (measured as SUVmax) at PET-CT.
Patients will be evaluated monthly during the treatment course and every 3 months after remission.
Adverse events will be assessed at each scheduled visit by physical examination and routine exams. Eventual adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.
Trial website
None
Trial related presentations / publications
None
Public notes
None

Contacts
Principal investigator
Name 82062 0
Dr Augusto Vaglio
Address 82062 0
Azienda Ospedaliero-Universitaria di Parma,
Nephrology Unit,
Via Gramsci 14
43126 Parma
Country 82062 0
Italy
Phone 82062 0
+39 0521 702013
Fax 82062 0
+39 0521 704701
Email 82062 0
augusto.vaglio@virgilio.it
Contact person for public queries
Name 82063 0
Dr Augusto Vaglio
Address 82063 0
Azienda Ospedaliero-Universitaria di Parma,
Nephrology Unit,
Via Gramsci 14
43126 Parma
Country 82063 0
Italy
Phone 82063 0
+39 0521 702013
Fax 82063 0
+39 0521 704701
Email 82063 0
augusto.vaglio@virgilio.it
Contact person for scientific queries
Name 82064 0
Dr Augusto Vaglio
Address 82064 0
Azienda Ospedaliero-Universitaria di Parma,
Nephrology Unit,
Via Gramsci 14
43126 Parma
Country 82064 0
Italy
Phone 82064 0
+39 0521 702013
Fax 82064 0
+39 0521 704701
Email 82064 0
augusto.vaglio@virgilio.it

No data has been provided for results reporting
Summary results
Not applicable