Primary Chemoablation of Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer Using UGN-102, a Mitomycin-Containing Reverse Thermal Gel (Optima II): A Phase 2b, Open-Label, Single-Arm Trial

Chevli, Kent; Shore, Neal D.; Trainer, Andrew; Smith, Angela; Saltzstein, Daniel R.; Ehrlich, Yaron; Raman, Jay D.; Friedman, Boris; D’Anna, Richard; Morris, David; Hu, Brian; Tyson, Mark D.; Sankin, Alexander; Kates, Max; Linehan, Jennifer; Scherr, Douglas; Kester, Steven; Verni, Michael; Chamie, Karim; Karsh, Lawrence I.; Cinman, Arnold; Meads, Andrew; Lahiri, Soumi; Malinowski, Madlen; Gabai, Nimrod; Raju, Sunil; Schoenberg, Mark; Seltzer, Elyse; Huang, William C.

doi:10.1097/ju.0000000000002186

Cited by 20 publications

(37 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a single-arm trial, 63 patients with low-grade, intermediate-risk NMIBC were treated with six, weekly instillations of UGN-102. At 12 months, 65% of patients had a CR ( 122 ). To further investigate UGN-102 a RCT is currently ongoing to compare a 6-week course of UGN-102 to TURBT only in patients with low-grade, intermediate-risk NMIBC ( 123 ).…”

Section: Resultsmentioning

confidence: 99%

“…The selectivity of these drugs should minimise their toxicity and side-effects ( 52 – 54 , 56 , 59 , 68 ). Chemohyperthermia and hydrogels are promising and may enhance the clinical efficacy of intravesical MMC delivery ( 107 , 122 ); with international BCG supply issues, improving MMC efficacy may be particularly important for patients with intermediate- and high-risk NMIBC ( 125 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Novel intravesical therapeutics in the treatment of non-muscle invasive bladder cancer: Horizon scanning

et al. 2022

View full text Add to dashboard Cite

IntroductionNon-muscle-invasive bladder cancer (NMIBC) is a common and heterogeneous disease; many patients develop recurrent or progress to muscle-invasive disease. Intravesical drug therapy is a pillar in the current management of NMIBC; notwithstanding, Mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) have numerous limitations including international supply issues, and local and systemic toxicity. Here we review novel intravesical therapeutic options and drug delivery devices with potential for clinical use in the treatment of NMIBC.MethodsPubMed, ClinicalTrials.gov and Cochrane Library searches were undertaken. Systematic reviews, meta-analyses, randomised controlled trials, single-arm clinical trials and national/international conference proceedings were included.ResultsNovel intravesical drugs, including chemotherapeutic agents, immune checkpoint inhibitors, monoclonal antibodies and gene therapies, have demonstrated varying efficacy in the treatment of NMIBC. Current evidence for the majority of treatments is mostly limited to single-arm trials in patients with recurrent NMIBC. Various novel methods of drug delivery have also been investigated, with encouraging preliminary results supporting the intravesical delivery of hyperthermic MMC and MMC hydrogel formulations.ConclusionsNovel therapeutic agents and drug delivery systems will be important in the future intravesical management of NMIBC. As our understanding of the molecular diversity of NMIBC develops, molecular subtyping will become fundamental in the personalisation of intravesical treatments. Further randomised studies are urgently required to investigate the efficacy of novel intravesical treatments and novel regimens, in comparison to current standards-of-care, particularly in the context of international BCG shortages.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Novel intravesical therapeutics in the treatment of non-muscle invasive bladder cancer: Horizon scanning

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Preliminary results from a phase 3 clinical trial (OLYMPUS study) exhibited that the UGN-101 was a successful chemoablative agent for treating low-grade BCa, and its safety was confirmed in a study by Matin et al [198,199]. The well-tolerated properties of UGN-102 as a mitomycin-containing reverse thermal gel (Optima II) were demonstrated in a phase 2b study by Chevli et al [200]. Moreover, chitosan could be developed into different forms, such as thin films, nanoparticles, sponges, and hydrogels.…”

Section: Novel Therapy 61 Novel Drug Delivery Systemmentioning

confidence: 97%

Advances in Diagnosis and Therapy for Bladder Cancer

2022

Cancers

View full text Add to dashboard Cite

Bladder cancer (BCa) is one of the most common and expensive urinary system malignancies for its high recurrence and progression rate. In recent years, immense amounts of studies have been carried out to bring a more comprehensive cognition and numerous promising clinic approaches for BCa therapy. The development of innovative enhanced cystoscopy techniques (optical techniques, imaging systems) and tumor biomarkers-based non-invasive urine screening (DNA methylation-based urine test) would dramatically improve the accuracy of tumor detection, reducing the risk of recurrence and progression of BCa. Moreover, intravesical instillation and systemic therapeutic strategies (cocktail therapy, immunotherapy, vaccine therapy, targeted therapy) also provide plentiful measures to break the predicament of BCa. Several exploratory clinical studies, including novel surgical approaches, pharmaceutical compositions, and bladder preservation techniques, emerged continually, which are supposed to be promising candidates for BCa clinical treatment. Here, recent advances and prospects of diagnosis, intravesical or systemic treatment, and novel drug delivery systems for BCa therapy are reviewed in this paper.

show abstract

“…Among 63 patients, 41 (65%) achieved CR at 3 months, of whom 39 (95%), 30 (73%) and 25 (61%) remained disease-free at 6, 9 and 12 months after treatment initiation. 17 Thirteen patients (32%) had documented disease recurrence. 17 In the current study, we examined changes in patient-reported side effects from UGN-102 through the primary trial endpoint of 3 months, and whether demographic and clinical characteristics were associated with changes.…”

Section: Turbt [ Transurethral Resection Of Bladder Tumormentioning

confidence: 99%

“…17 Thirteen patients (32%) had documented disease recurrence. 17 In the current study, we examined changes in patient-reported side effects from UGN-102 through the primary trial endpoint of 3 months, and whether demographic and clinical characteristics were associated with changes. We also interviewed 10 patients about their side effects and experiences with UGN-102 to better understand tolerability, which will be an important consideration for future patients choosing among NMIBC treatment options.…”

Section: Turbt [ Transurethral Resection Of Bladder Tumormentioning

confidence: 99%

Minimal Patient-Reported Side Effects for a Chemoablative Gel (UGN-102) Used as Frontline Treatment in Adults with Nonmuscle-Invasive Bladder Cancer

Stover

Basak

Mueller³

et al. 2022

Journal of Urology

Self Cite

View full text Add to dashboard Cite

Purpose:Optima II (“OPTimized Instillation of Mitomycin for Bladder Cancer Treatment,” clinicaltrials.gov: NCT03558503) was a phase 2b trial evaluating a nonsurgical alternative as a primary treatment for nonmuscle‐invasive bladder cancer (NMIBC). Patients received 6 weekly instillations of UGN-102, a mitomycin-containing reverse thermal gel. This is the first study to report on patient-reported side effects of UGN-102.Materials and Methods:Sixty-three patients enrolled in Optima II from 20 sites. Of these 63 patients, 44 were in the cohort completing a quarterly patient-reported outcome measure assessing side effects. Changes in side effects were evaluated using the Wilcoxon signed-rank test. Associations of 3-month outcomes with demographic and clinical characteristics were examined with regression, controlling for baseline values. Ten of 44 patients (23%) were interviewed after the trial to understand tolerability for future patients making treatment decisions. Transcripts were double-coded using standard methods.Results:In the patient-reported outcome measure cohort (44), 61% were men, 57% aged 65+ years and 89% were non-Hispanic White. UGN-102 did not cause decrements in patient-reported urinary symptoms, bloating/flatulence or malaise at the primary endpoint of 3 months. Sexual function mildly worsened. Future health worries improved. Demographics were not correlated with changes. Clinically, sexual function was correlated with new NMIBC and bloating/flatulence was associated with transurethral resection of bladder tumor within 12 months. In interviews, patients appreciated a nonsurgical alternative, would recommend the gel to other patients and would choose the gel over surgery.Conclusions:A nonsurgical, chemoablative gel (UGN-102) used as a primary treatment for NMIBC offers a more patient-centered therapeutic approach than standard treatments.

show abstract

Primary Chemoablation of Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer Using UGN-102, a Mitomycin-Containing Reverse Thermal Gel (Optima II): A Phase 2b, Open-Label, Single-Arm Trial

Abstract: Primary chemoablation of low-grade intermediate-risk non-muscle-invasive bladder cancer using UGN-102, a mitomycin-containing reverse thermal gel (OPTIMA II): a phase 2b, open-label, single-arm trial,

Cited by 20 publications

References 23 publications

Novel intravesical therapeutics in the treatment of non-muscle invasive bladder cancer: Horizon scanning

Novel intravesical therapeutics in the treatment of non-muscle invasive bladder cancer: Horizon scanning

Advances in Diagnosis and Therapy for Bladder Cancer

Minimal Patient-Reported Side Effects for a Chemoablative Gel (UGN-102) Used as Frontline Treatment in Adults with Nonmuscle-Invasive Bladder Cancer

Contact Info

Product

Resources

About