This study has 4 objectives: to (1) describe the trained immunity response that is triggered by intravesical BCG therapy in high-risk NMIBC patients; (2) compare the trained immune response between patients with and without tumor recurrence within 1…
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
- Bladder and bladder neck disorders (excl calculi)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Study parameters include (i) histone 3 lysine 4 (H3K4) trimethylation (me3),
H3K9me3, and H3K27 acetylation levels at the TNF-*, IL-6 and IL1-b promoters in
circulating monocytes during BCG treatment; (ii) TNF-*, IL-6 and IL-1b levels
produced by ex vivo stimulated monocytes during treatment, (iii) DNA variant
genotypes and molecular bladder tumor subtypes, (iv) CyPRIT score, (v) (time
to) tumor recurrence.
Secondary outcome
NA
Background summary
Intravesical Bacillus Calmette-Guérin (BCG) therapy is considered standard
treatment in high-risk non-muscle invasive bladder cancer (NMIBC) to prevent
tumor recurrence and maybe even progression. The treatment protocol entails an
induction cycle of 6 weekly bladder instillations and a number of maintenance
cycles in the 1-3 years thereafter. The immune system is thought to play an
important role in the response to BCG but the exact working mechanism is
unknown. Also, it is not yet possible to identify patients who do (not) benefit
from BCG. Recently, it was shown in vitro and ex vivo that response to BCG is
mediated by epigenetic reprogramming of innate immune cells (*trained
immunity*) and that response to BCG may be predicted via a urinary cytokine
panel (CyPRIT).
Study objective
This study has 4 objectives: to (1) describe the trained immunity response that
is triggered by intravesical BCG therapy in high-risk NMIBC patients; (2)
compare the trained immune response between patients with and without tumor
recurrence within 1 year after BCG therapy start; (3) explore the association
between common germline DNA variants and molecular tumor subtypes and the
trained immunity response; (4) replicate the reported predictive value of the
CyPRIT score for BCG response (1-year recurrence).
Study design
This is a multi-centre, observational cohort study with at least 1 year
follow-up for included patients (there is no treatment intervention; treatment
is according usual clinical practice).
Study burden and risks
The burden and risks associated with participation in the study are considered
acceptable. The number of hospital visits is equal to what patients with these
criteria is offered when they are not participating in this study. Extra in
this study are the collection of (1) urine samples prior to the 1st and prior
to and 4 to 8 hours after the 6th BCG induction instillation and prior to and
after the last instillation in the first maintenance cycle (5 urine samples);
(2) blood samples prior to the 1st and after the 2nd and 6th BCG instillation
of the induction cycle and prior to the 1st and after the 3rd instillation of 3
maintenance cycles (9 blood samples). Participation has no direct benefit for
patients.
This study can only be performed in patients with non-muscle invasive bladder
cancer and that receive BCG installation therapy for the treatment of this
disease.
Geert Grooteplein Noord 21
Nijmegen 6500HB
NL
Geert Grooteplein Noord 21
Nijmegen 6500HB
NL
Listed location countries
Age
Inclusion criteria
1. Presence of high-grade Ta or T1 urothelial carcinoma of the bladder with or without carcinoma in situ; tumor can be primary or recurrent
2. Able to communicate in Dutch, and read and understand the patient information and informed consent form and fill out questionnaires
3. Signed and dated informed consent form
4. Complete resection of (visible) tumor at start of BCG therapy as determined via re-TURT or negative cystoscopy/cytology (at most 6 weeks prior to BCG therapy initiation)
Exclusion criteria
1. Any previous intravesical BCG therapy
2. Presence of primary CIS only
3. Presence of histopathologically proven muscle-invasive urothelial carcinoma of the bladder at first or re-TUR surgical specimens
4. Presence of tumor stage cN1 of cM1 as assessed by CT-thorax/abdomen
5. Presence of any upper urinary tract tumors
6. Histology subtype of resected tumor is not predominant urothelial carcinoma
7. Presence of another malignancy other than basal cell carcinoma of the skin or prostate cancer under active surveillance
8. Presence of pregnancy or lactation
9. Presence of active tuberculosis, any form of immunodeficiency (e.g. HIV + serology, transplant recipients) and/or any other contraindication of BCG therapy
10. Patients who have received any systemic cytostatic agents within the last 3 months
11. Patients younger than 18 and older than 85 years of age
12. Patients with uncontrollable urinary tract infection
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL60341.091.17 |