Bladder (Urothelial, Transitional Cell) Cancer, Bladder (Urothelial, Transitional Cell) Cancer Superficial (Non-Invasive), Urologic Cancer, Urothelial Carcinoma Bladder, Urothelial Carcinoma Recurrent
Conditions
Brief summary
This is a Phase 3, open-label single-arm trial designed to evaluate the safety and efficacy of NDV-01 (sustained-release gemcitabine-docetaxel) in adult participants with NMIBC with CIS who have failed BCG therapy and who have failed first-line therapy for BCG-unresponsive NMIBC (approved or in development) and are recommended for radical cystectomy.
Detailed description
This is a Phase 3, open-label single-arm trial designed to evaluate the safety and efficacy of NDV-01 (sustained-release gemcitabine-docetaxel) in adult participants with NMIBC with CIS who have failed BCG therapy and who have failed first-line therapy for BCG-unresponsive NMIBC (approved or in development) and are recommended for radical cystectomy. Participants will receive an induction course and then monthly maintenance courses of NDV-1 (sustained-release gemcitabine-docetaxel) through 3 years, if there is no disease recurrence. Participants will received an induction course of NDV-01 (6-bi-weekly intravesical instillations). Those who achieve a complete response (CR) at 3 months will be eligible for monthly maintenance instillations through year 3. Disease status will be assessed using urine cytology, cystoscopy, and directed TURBT/biopsy (if indicated) every 3 months for the first 2 years after randomization or until disease recurrence.
Interventions
Intravesical instillation of NDV-01 (sustained-release gemcitabine-docetaxel)
Sponsors
Relmada Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A Phase 3, Open-label Single-arm Study of NDV-01
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
* BCG-unresponsive NMIBC with CIS of the bladder, with or without coexisting papillary Ta/T1 tumor(s) who are ineligible for or have elected not to undergo cystectomy at the time of enrollment and have experienced 1) CIS disease within 12 months of treatment. * Participants with BCG-unresponsive disease must have received up to two first-line therapies or BCG-unresponsive disease and who are recommended for radical cystectomy. Such therapies may include agents approved or in development (e.g., pembrolizumab, nadofaragene firodenovec, nogapendekin alfa inbakicept-pmln, cretostimogene grenadenorepvec, detalimogene voraplasmid, TARA-002, gemcitabine intravesical system (INLEXZO®), gemcitabine, MMC, or valrubicin monotherapy. Participants will have demonstrated recurrence or intolerance after one or two first-line therapy(ies). * All specimens must be predominantly urothelial (transitional cell) carcinoma with or without squamous or glandular differentiation. Pure squamous or glandular tumors will not be included. Participants with less than 10% micropapillary histology will be included. All other variant histology (e.g. plasmacytoid, small cell, nested, trophoblastic variants) will not be included.
Exclusion criteria
\- Has had urothelial carcinoma outside of the urinary bladder (i.e., urethra, ureter, or renal pelvis) or has a predominant histological variant of UC. Ta/any T1, CIS of the upper urinary tract is allowable if treated with complete nephroureterectomy more than 24 months prior to initiating study: Participant has tumor(s) involving the prostatic urethra (ductal or stromal); N+ and/or M+ per computerized tomography (CT)/Magnetic Resonance Imagery (MR) urography. History of prior T2/T3 urothelial carcinoma of the bladder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the efficacy of NDV-01 (determined by complete response [CR] anytime) administered by intravesical instillation in patients with BCG-unresponsive NMIBC who have recurred after first-line intravesical therapy (approved or in development). | 12 months | Percentage of participants with CR at anytime based on cystoscopy, urine cytology, and biopsies. Protocol-driven mapping biopsies (as assessed by central pathology) will be performed at 12 months |
Outcome results
None listed