Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ongoing, recruitment ended
Participants planned
314
Countries
3
Sites
11
Urothelial cancer
The trial aims to evaluate the potential clinical impact of a new regimen with reduction of dwell time during once-weekly BCG instillations for 6 weeks followed by maintenance therapy for 12 months with regards to side effects, adherence to instillation regimen, and oncological outcome.
Key facts
- Sponsor
- Aarhus University Hospital
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13], Diseases [C] - Male Urogenital Diseases [C12]
- Trial duration
- 3 Feb 2021 → ongoing
- Decision date (initial)
- 2023-09-13
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- medac GmbH
External identifiers
- EU CT number
- 2023-505936-37-00
- EudraCT number
- 2020-003112-27
- ClinicalTrials.gov
- NCT04701151
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Efficacy
The trial aims to evaluate the potential clinical impact of a new regimen with reduction of dwell time during once-weekly BCG instillations for 6 weeks followed by maintenance therapy for 12 months with regards to side effects, adherence to instillation regimen, and oncological outcome.
Secondary objectives 3
- To evaluate the safety of the new regime, so that patients are not treated with an inferior treatment with risk of earlier progression and recurrence.
- To evaluate if there is a higher number of completed instillations
- To evaluate if the treatment is more tolerated with fewer side effects both local and systemic
Conditions and MedDRA coding
Urothelial cancer
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Nordic Urothelial Cancer Reseach Group Study on Reduced BCG Dwell-Time in HIgh Risk NMIBC The study is designed as a multi-center, multi-national, two-armed, randomized, open-label, investigator initiated clinical controlled phase IV trial.
|
Randomised Controlled | None | Control group: The study subjects will be treated according to guidelines with BCG instillation therapy once weekly for 6 weeks and subsequent 1 year maintenance therapy (6 + 3x3) with 2 hours of dwell time. There may be times when study subjects cannot comply withe the 2 hour dwell time, but they will be encouraged to aim for a 2 hour dwell time at next instillation. Side effects are registered by ystudy subjects on a daily basis by self-reported questionnaire developed specifically for this study under both induction and maintenance therapy. Reported side effects will be handled in accordance with the study algorithm. if Grade 3 (severe) side effects occour treatment will be terminated. QoL questionnaires will be sent out at baseline, at end of induction and at 3, 6, and 12 months. Intervention group: The study subjects will be assigned to BCG instillation therapy once weekly for 6 weeks and subsequent 1 year maintenance therapy (6 + 3x3) of which dwell time for the first of the 6 instillationsis 2 hours. Side effects are registered by study subjects on a daily basis by self-reported questionnaire developed specifically for this study during both induction and maintenance therapy. If side effects are registered before the 2nd and all subsequent instillations, study subjects will be reduced in dwell time in accordance with the study algorithm. If Dwell time had been reduced, it will remain so for all subsequent instillations (induction and maintenance), even if a decrease in symptoms should occur. If symptoms increase this could lead to a further reductio in dwell time. If no side effects are reported dwell time will remain at 2 hours. The decision of length of dwell time will be based on the previous weeks relf-reported questionnaires. If Grade 3 (severe) side effects occour treatment will be terminated. QoL questionnaires will be sent out at baseline, at end of induction and at 3, 6, and 12 months. |
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2022-500316-19-00 | Nordic Urothelial Cancer Research Group Study on Reduced BCG Dwell-Time in High Risk NMIBC | Aarhus University Hospital |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- above 18 of age at the time of signing the informed consentform
- Signed informed consent form
- Patients with NMIBC where BCG therapy including maintanence for 1 year is planned for one of the following histopathological findings: Ta high grade without CIS; CIS with or without previous or concomitant Ta tumours; T1 with or without CIS
- is, according to the investigator's judgement, able to comply with the trial protocol
- Ability to understand the patient information sheet orally and in writing
Exclusion criteria 24
- previous BCG instillation with the last 2 years, due to risk of not having vcleared potential previous side effects
- Immune suppressingmedication (cancer therapy e.g. cytostatic medicinal products, radiation, local and systemic steroids e.g. prednisolone is permitted)
- Reduced immune response (leukaemia, lymphoma)
- Known allergy to BCG
- Hiv infection if untreated or uncontrolled
- Signs of active tuberculosis
- Any type of previous radiation therapy involving the bladder
- Concomitant invasive cancer within 5 years other than non-melanoma skin cancer and prostate cancer without metastasis
- Current urinary tract infection
- Patient with visible hematuria
- Current alcohol and/or drug abuse
- T1 tumors where re-resection has not been performed
- Mental or legal incapatitation or another condition which impair the subjects ability to participate
- Participation in another interventional clinical study and treatment with another investigational product 30 days prior to randomization
- Pregnancy or breastfeeding
- TURB, bladder biopsy or traumatic catheterization with 2 weeks
- Previous or current MIBC
- Progression, defuned as progression to T1-, T2+ tumour or cystectomy irrespectively of indication or developement of metastatic urothelial cancer irrespectively of tumour stage
- Contraindications to BCG
- Incontinence
- Need for catheter at the time of instillation
- Bilateral nephrostomy catheters; unilateral nephrostomy catherter is allowed IF permanent for the duration of all istillations with BCG AND a normally functioning kidney
- Female study subjects of childbearing age: unless they use highly effective methods of contraception from the first BCG instillations untill 14 days after last dose of BCG treatment, difined as total abstinence, female sterilization, oral contraceptives, or intrauterine contraceptive device
- Male study subjects; unless they use highly effective methods of contraception from the first BCG instillation until 14 days after the last dose pf BCG treatment, defined as toatl abstinence or use of condoms
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Number of study subjects completing all 6 induction instillations and subsequent maintenance instillations for 12 months (6+3x3)
Secondary endpoints 11
- Recurrence rate within 24 months in study subjects with initial complete response
- Progression rate within 24 months and 60 months
- disease specific survival within 24 months and 60 months
- Overall survival 24 months and 60 months
- Total number of BCG instillations per study subject
- Number of study subjects completing all 6 induction instillations
- Number of BCG instillations given with full dwell time of 2 hours per study subject
- Number of instillations per study subject postsponed 1 week or more because of side effects
- Number of study subjects where instillations is stopped because of local side effects
- Number of study subjects where instillations is stopped because of systemic side effects
- Number of study subjects undergoing re-induction therapy within 24 months because of recurrent or persistent disease
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
BCG-medac Pulver und Lösungsmittel zur Herstellung einer Suspension zur intravesikalen Anwendung
PRD1823716 · Product
- Active substance
- Bcg (Bacillus Calmette-Guérin) Bacteria
- Pharmaceutical form
- SUSPENSION FOR INJECTION
- Route of administration
- INTRAVESICAL USE
- Max daily dose
- 50 mg/ml milligram(s)/millilitre
- Max total dose
- 750 mg/ml milligram(s)/millilitre
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- L03AX03 — BCG VACCINE
- Marketing authorisation
- BE236056
- MA holder
- MEDAC GESELLSCHAFT FÜR KLINISCHE SPEZIALPRÄPARATE MBH (WEDEL)
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Aarhus University Hospital
- Sponsor organisation
- Aarhus University Hospital
- Address
- Palle Juul-Jensens Boulevard 99
- City
- Aarhus N
- Postcode
- 8200
- Country
- Denmark
Scientific contact point
- Organisation
- Aarhus University Hospital
- Contact name
- Charlotte Graugaard-Jensen
Public contact point
- Organisation
- Aarhus University Hospital
- Contact name
- Charlotte Graugaard-Jensen
Third parties 6
| Organisation | City, country | Duties |
|---|---|---|
| Frederiksberg Hospital ORG-100028217
|
Frederiksberg, Denmark | On site monitoring |
| Odense University Hospital ORG-100007716
|
Odense C, Denmark | On site monitoring |
| Karolinska University Hospital ORG-100000573
|
Huddinge, Sweden | On site monitoring |
| Landspitali ORG-100023489
|
Reykjavik, Iceland | On site monitoring |
| Region Oerebro Laen ORG-100010829
|
Orebro, Sweden | On site monitoring |
| Aarhus University ORG-100028380
|
Aarhus N, Denmark | On site monitoring |
Locations
3 EU/EEA countries · 11 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Ongoing, recruitment ended | 214 | 7 |
| Iceland | Ongoing, recruitment ended | 20 | 1 |
| Sweden | Ongoing, recruitment ended | 80 | 3 |
| Rest of world | — | 0 | — |
Investigational sites
Aarhus Universitetshospital
of Urology, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N
Herlev Hospital
of Urology, Borgmester Ib Juuls Vej 1, 2730, Herlev
Rigshospitalet
of Urology, Inge Lehmanns Vej 7, 2100, Copenhagen Oe
Odense University Hospital
of Urology, J. B. Winsloews Vej 4, 5000, Odense C
Aalborg University Hospital
of Urology, Hobrovej 18-22, 9000, Aalborg
Region Sjaelland
of Urology, Sygehusvej 10, 4000, Roskilde
Region Midtjylland
of Urology, Hospitalsparken 15, 7400, Herning
Region Oerebro Laen
of Urology, Sodra Grev Rosengatan, 701 85, Orebro
Sahlgrenska University Hospital-Vastra Gotalandsregionen
of Urology, Bruna Straket 16, 413 46, Gothenburg
Karolinska University Hospital
of Urology, Halsovagen, Flemingsberg, Huddinge
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Denmark | 2021-02-03 | 2021-02-03 | 2024-06-21 | ||
| Iceland | 2022-03-15 | 2022-03-15 | 2024-06-21 | ||
| Sweden | 2022-10-27 | 2022-10-27 | 2024-06-21 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 19 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | Dwell Time protocol CTIS version_ | 1.13 |
| Protocol (for publication) | Dwell Time protocol with track changes | 1.14 |
| Protocol (for publication) | Dwell Time protocol without track changes | 1.14 |
| Recruitment arrangements (for publication) | Part II confirmation of aspects | 1 |
| Recruitment arrangements (for publication) | Recruitment and Informed consent procedure | 1 |
| Recruitment arrangements (for publication) | Recruitment materials | 1 |
| Subject information and informed consent form (for publication) | Deltagerinformation | 1.4 |
| Subject information and informed consent form (for publication) | Deltagerinformation with track changes | 1.5 |
| Subject information and informed consent form (for publication) | Deltagerinformation without track changes | 1.5 |
| Subject information and informed consent form (for publication) | Samtykkeerklring | 1 |
| Subject information and informed consent form (for publication) | Samtykkeerklring 23JUN2020_03OCT2023_without track changes | 1.0 |
| Subject information and informed consent form (for publication) | Samtykkeerklring ved afbrydelse af studiemedicin | 1 |
| Subject information and informed consent form (for publication) | Samtykkeerklring ved afbrydelse af studiemedicin with track changes | 1 |
| Subject information and informed consent form (for publication) | Samtykkeerklring ved afbrydelse af studiemedicin without track changes | 1 |
| Subject information and informed consent form (for publication) | Samtykkeerklring with track changes | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | BCG-medac common SPC v1-2022 | 1 |
| Synopsis of the protocol (for publication) | NordReg Dwell time fylgibref til Lyfjastofnunar | 1 |
| Synopsis of the protocol (for publication) | Protocol synopsis | 1 |
| Synopsis of the protocol (for publication) | Sammanfattning av studieprotokoll pa svenska | 1 |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-06-20 | Acceptable 2023-07-27
|
2023-07-27 | |
| 2 | SUBSEQUENT ADDITION OF MSC | APP-2 | 2023-08-17 | Denmark | Acceptable 2023-07-27
|
2023-09-13 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2023-10-23 | Denmark | Acceptable 2023-12-11
|
2023-12-14 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-11-25 | Denmark | Acceptable 2023-12-11
|
2025-11-25 |
| 5 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-12-03 | Denmark | Acceptable 2025-12-22
|
2025-12-22 |