A Phase 3, Randomized, Open-label, Multi-center Study Evaluating the Efficacy and Safety of TAR-200 Versus Investigator’s Choice of Intravesical Chemotherapy in Participants Who Received Bacillus Calmette-Guérin (BCG) and Recurred with High-risk Non-Muscle-Invasive Bladder Cancer (HR-NMIBC) and Who Are Ineligible for or Elected Not to Undergo Radical Cystectomy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Janssen Cilag International

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 May 2024 → ongoing

Decision date (initial)

2024-05-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacodynamic, Pharmacokinetic, Therapy

To compare disease-free survival (DFS)

Conditions and MedDRA coding

High-Risk Non-muscle-invasive Bladder Cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Histologically confirmed diagnosis by local pathology (within 90 days of documented informed consent) of recurrent, papillary-only HR-NMIBC (defined as HG Ta or any T1, no CIS).
2. Participants with variant histologic subtypes are allowed if tumor(s) demonstrate urothelial (transitional cell histology) predominance. However, neuroendocrine, and small cell variants will be excluded.
3. All visible tumor completely resected prior to randomization. Urine cytology must not be positive or suspicious for HG UC before randomization. For participants with lamina propria invasion (T1) on the Screening biopsy/TURBT, muscularis propria must be present to rule out MIBC.
4. Participants must have received at least 5 of 6 induction doses of BCG (adequate induction) with or without maintenance therapy.
5. Diagnosis of recurrent, papillary-only HR-NMIBC (defined as HG Ta or any T1, no CIS) must be within 12 months of the last dose of BCG therapy.
6. Participants must be ineligible for or have elected not to undergo RC.

Exclusion criteria 4

1. Presence of CIS at any point from time of diagnosis of papillary-only HR-NMIBC recurrence to randomization. Additionally, presence or history of histologically confirmed, muscle-invasive, locally advanced, nonresectable, or metastatic UC (ie, T2, T3, T4, N+, and/or M+).
2. Must not currently have UC or histological variant at any site outside of the urinary bladder. UC of the upper urinary tract (including renal pelvis and ureter) is allowable if treated with complete nephroureterectomy more than 24 months prior to randomization with no evidence of recurrence.
3. N+ and/or M+ per BICR of CT/MR Urography.
4. Received serial intravesical therapy or systemic therapy from the time of histologic diagnosis of recurrent HR-NMIBC to date of randomization. Immediate post-TURBT single-dose per-operative intravesical chemotherapy is allowed in accordance with institutional guidelines.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. DFS will be measured as the time from randomization to the time of the first recurrence of HR-NMIBC (HG Ta, any T1 or CIS), progression, or death due to any cause, whichever occurs first. Recurrence or progression of DFS events will be determined by central disease assessments of urine cytology, bladder biopsy, or imaging, as applicable.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Janssen Cilag International

Sponsor organisation

Janssen Cilag International

Address

Turnhoutseweg 30

City

Beerse

Postcode

2340

Country

Belgium

Scientific contact point

Organisation

Janssen Cilag International

Contact name

CTIS Point of Contact

Public contact point

Organisation

Janssen Cilag International

Contact name

CTIS Point of Contact

Third parties 12

Locations

7 EU/EEA countries · 43 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 110 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

14 submissions — initial application plus substantial / non-substantial modifications