scholarly journals 426 A phase 3, single-arm study of CG0070 in subjects with non-muscle invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guerin (BCG)

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A456-A456
Author(s):  
Ed Uchio ◽  
Donald Lamm ◽  
Neal Shore ◽  
Paul Anderson ◽  
Tran Ben ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Urine Cytology ◽  
Invasive Bladder Cancer ◽  
Clinical Activity ◽  
List Type ◽  
Open Label ◽  
Muscle Invasive Bladder Cancer ◽  
Phase 3 ◽  
Free Survival ◽  
Muscle Invasive

BackgroundCG0070 is a serotype 5 adenovirus engineered to express GM-CSF and replicate in cells with mutated or deficient RB, with response rates (RR) of approximately 45% observed in patients with recurrent NMIBC after BCG.1 2 This single arm phase 3 study (NCT04452591) was launched to confirm the clinical activity of CG0070 in patients with BCG Unresponsive NMIBC.Methods110 patients with BCG-unresponsive CIS with or without concurrent Ta or T1 disease will be treated with intravesical (IVe) CG0070 at a dose of 1x10e12 vp. CG0070 will be administered as follows: induction weekly x 6 followed by weekly x 3 maintenance instillations at months 3, 6, 9, 12, and 18. Patients with persistent CIS or HG Ta at 3 m may receive re-induction with weekly x 6 CG0070. Assessment of response will include q 3 m cystoscopy with biopsy of areas suspicious for disease, urine cytology, CTU/MRU, and mandatory bladder mapping at 12 m. Detection of high grade disease within the bladder will be enumerated as recurrence or non-response. The primary endpoint of the study is CR at any time on study as assessed by biopsy (directed to cystoscopic abnormalities and mandatory mapping at 12 m), urine cytology, and radiography, as above. Secondary endpoints include CR at 12 m, duration of response, progression free survival, cystectomy free survival and safety. Correlative assessments include changes in the tumor immune microenvironment, systemic immune induction as reflected in the peripheral blood and urine, as well as viral replication and transgene expression. Baseline expression of coxsackie adenovirus receptor, E2F transcription factor as well as anti-adenovirus antibody titer will be correlated with tumor response. Study enrollment globally is ongoing.Trial RegistrationNCT04452591ReferencePackiam VT, Lamm DL, Barocas DA, Trainer A, Fand B, Davis RL 3rd, Clark W, Kroeger M, Dumbadze I, Chamie K, Kader AK, Curran D, Gutheil J, Kuan A, Yeung AW, Steinberg GD. An open label, single-arm, phase II multicenter study of the safety and efficacy of CG0070 oncolytic vector regimen in patients with BCG-unresponsive non-muscle-invasive bladder cancer: Interim results. Urol Oncol 2018;36:440–447.Ethics ApprovalCASTLE IRB: BOND-003 (CG3002S)

scholarly journals Non-maintenance intravesical Bacillus Calmette–Guérin induction therapy with eight doses in patients with high- or highest-risk non-muscle invasive bladder cancer: a retrospective non-randomized comparative study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Makito Miyake ◽  
◽  
Kota Iida ◽  
Nobutaka Nishimura ◽  
Tatsuki Miyamoto ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Propensity Score ◽  
Invasive Bladder Cancer ◽  
Rank Test ◽  
Bacillus Calmette Guerin ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Landmark Analyses ◽  
Muscle Invasive ◽  
Group B

Abstract Background To explore possible solutions to overcome chronic Bacillus Calmette–Guérin (BCG) shortage affecting seriously the management of non-muscle invasive bladder cancer (NMIBC) in Europe and throughout the world, we investigated whether non-maintenance eight-dose induction BCG (iBCG) was comparable to six-dose iBCG plus maintenance BCG (mBCG). Methods This observational study evaluated 2669 patients with high- or highest-risk NMIBC who treated with iBCG with or without mBCG during 2000–2019. The patients were classified into five groups according to treatment pattern: 874 (33%) received non-maintenance six-dose iBCG (Group A), 405 (15%) received six-dose iBCG plus mBCG (Group B), 1189 (44%) received non-maintenance seven−/eight-dose iBCG (Group C), 60 (2.2%) received seven−/eight-dose iBCG plus mBCG, and 141 (5.3%) received only ≤5-dose iBCG. Recurrence-free survival (RFS), progression-free survival, and cancer-specific survival were estimated and compared using Kaplan–Meier analysis and the log-rank test, respectively. Propensity score-based one-to-one matching was performed using a multivariable logistic regression model based on covariates to obtain balanced groups. To eliminate possible immortal bias, 6-, 12-, 18-, and 24-month conditional landmark analyses of RFS were performed. Results RFS comparison confirmed that mBCG yielded significant benefit following six-dose iBCG (Group B) in recurrence risk reduction compared to iBCG alone (groups A and C) before (P < 0.001 and P = 0.0016, respectively) and after propensity score matching (P = 0.001 and P = 0.0074, respectively). Propensity score-matched sequential landmark analyses revealed no significant differences between groups B and C at 12, 18, and 24 months, whereas landmark analyses at 6 and 12 months showed a benefit of mBCG following six-dose iBCG compared to non-maintenance six-dose iBCG (P = 0.0055 and P = 0.032, respectively). There were no significant differences in the risks of progression and cancer-specific death in all comparisons of the matched cohorts. Conclusions Although non-maintenance eight-dose iBCG was inferior to six-dose iBCG plus mBCG, the former might be an alternative remedy in the BCG shortage era. To overcome this challenge, further investigation is warranted to confirm the real clinical value of non-maintenance eight-dose iBCG.

scholarly journals LBA27 PHASE 3 STUDY OF VICINIUM IN BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER: INITIAL RESULTS

2018 ◽  
Vol 199 (4S) ◽  
Author(s):  
Rian Dickstein ◽  
Ning Wu ◽  
Barrett Cowan ◽  
Curtis Dunshee ◽  
Michael Franks ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Phase 3 ◽  
Muscle Invasive ◽  
Initial Results

scholarly journals Biomarkers in Bladder Cancer Surveillance

2021 ◽  
Vol 8 ◽  
Author(s):  
Sukumar S. Sugeeta ◽  
Anand Sharma ◽  
Kenrick Ng ◽  
Arvind Nayak ◽  
Nikhil Vasdev
Keyword(s):  
Bladder Cancer ◽  
Clinical Trials ◽  
Prospective Studies ◽  
Urine Cytology ◽  
Cancer Surveillance ◽  
Invasive Bladder Cancer ◽  
Low Grade ◽  
Protein Biomarkers ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Aim: This is a narrative review with an aim to summarise and describe urinary biomarkers in the surveillance of non-muscle-invasive bladder cancer (NMIBC). It provides a summary of FDA-approved protein biomarkers along with emerging ones which utilise genetic, epigenetic and exosomal markers. We discuss the current limitations of the available assays.Background: Current guidelines advice a combination of cystoscopy, imaging,and urine cytology in diagnosis and surveillance. Although cytology has a high specificity, it is limited by low sensitivity particularly in low grade tumours. There are six FDA-approved urinary assays for diagnosis and surveillance of bladder cancer. They have shown to improve sensitivity and specificity to be used alongside cytology and cystoscopy but have a lower specificity in comparison to cytology and false positives often occur in benign conditions. Recent developments in laboratory techniques has allowed for use of markers which are RNA-, DNA-based as well as extracellular vesicles in the past decade.Methods: Using the PubMed/Medline search engines as well as Google Scholar, we performed an online search using the terms “bladder cancer,” “non-muscle invasive bladder cancer,” and “urine biomarkers” with filter for articles in English published up to May 2021. Systematic reviews and original data of clinical trials or observational studies which contributed to the development of the biomarkers were collated.Results: Biomarkers identified were divided into FDA-approved molecular biomarkers, protein biomarkers and gene-related biomarker with a table summarising the findings of each marker with the most relevant studies. The studies conducted were mainly retrospective. Due to the early stages of development, only a few prospective studies have been done for more recently developed biomarkers and limited meta-analyses are available.Therefore a detailed evaluation of these markers are still required to decide on their clinical use.Conclusion: Advancements of analytical methods in BC has driven the research towards non-invasive liquid-based biomarkers in adjunct to urine cytology. Further large prospective studies are required to determine its feasibility in a clinical setting as they are not effective when used in isolation as they have their limitation. With the ongoing pandemic, other than reduction in costs and increased accuracy, the need for biomarkers to cope with delay in cystoscopies in diagnosis and surveillance is crucial. Thus clinical trials with direct comparison is required to improve patient care.

Multi-institutional review of sequential intravesical gemcitabine and mitomycin C chemotherapy for non-muscle-invasive bladder cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 294-294
Author(s):  
Andrew J. Lightfoot ◽  
Benjamin N. Breyer ◽  
Henry M. Rosevear ◽  
Badrinath Konety ◽  
Michael A. O'Donnell
Keyword(s):  
Bladder Cancer ◽  
Mitomycin C ◽  
Median Time ◽  
Combination Chemotherapy ◽  
Invasive Bladder Cancer ◽  
Intravesical Therapy ◽  
Recurrence Free Survival ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive

294 Background: Combination chemotherapy is the standard of care for neoadjuvant, adjuvant, and metastatic bladder cancer due to increased efficacy when compared to monotherapy. We report our experience with sequential intravesical combination chemotherapy using gemcitabine and mitomycin C (MMC) for non-muscle invasive bladder cancer (NMIBC). Methods: We performed a multi-institutional retrospective review of 47 consecutive patients who received 6 weekly treatments with sequential gemcitabine (1g) and mitomycin C (40mg) chemotherapy for NMIBC. Thirty patients received treatment at University of Iowa, 14 at UCSF and 3 at University of Minnesota. Results: A total 47 patients (median age 70, range 32-85; 36 males, 11 females) previously failing a median of 2 intravesical treatments were reviewed. The complete response (CR), 1-year recurrence-free survival (1-RFS) and 2-year recurrence-free survival (2-RFS) for all patients was 68%, 48% and 38%, respectively. In all, 14 of 47 patients (30%) remain free of recurrence with a median time to followup of 26 months (range 6-80 months). The median time to recurrence for all patients who recurred was 4 months (range 1-33 months). Ten patients required cystectomy. Conclusions: Sequential intravesical combination chemotherapy using gemcitabine and MMC appears to be a useful treatment for patients with a history of NMIC which has failed BCG or other intravesical therapy, in addition to patients with intermediate and high-risk disease.

Effectiveness and safety of valrubicin in non–muscle-invasive bladder cancer following reintroduction: Results from a medical chart review study.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 296-296
Author(s):  
Michael S. Cookson ◽  
Christine Francis Lihou ◽  
Samira Q. Harper ◽  
Thomas Li ◽  
Surya Chitra ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Concomitant Medication ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
The United States ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive

296 Background: Valrubicin was approved in the United States in 1998, removed from the market in 2002 because of manufacturing issues, and reintroduced in 2009. We report secondary outcomes and concomitant medication use from a US multicenter, observational, retrospective study. Methods: Medical records of adult patients with non–muscle-invasive bladder cancer (NMIBC) who used valrubicin were abstracted (March–September 2011). Kaplan-Meier analyses were performed for disease-free survival (DFS), progression-free survival (PFS), worsening-free survival (WFS), cystectomy-free survival (CFS), and time to cystectomy. Results: 113 patients (mean age, 73.7 years) received intravesical valrubicin (median, 6 instillations [range, 2–18]). 107 patients (94.7%) received >3 instillations; 97 (85.8%) completed the full course of therapy (≥6 instillations). DFS was 51.6% (95% CI, 40.9%–61.3%) at 3 months, 30.4% (95% CI, 20.4%–41.1%) at 6 months, and median DFS was 3.5 months (95% CI, 2.5–4.0). PFS was 97.6% (95% CI, 90.9%–99.4%) at 3 months, 87.2% (95% CI, 75.4%–93.5%) at 6 months, and median PFS was 18.2 months (95% CI, 17.2–19.0). WFS was 47.4% (95% CI, 37.2%–57.0%) at 3 months and 28.1% (95% CI, 18.8%–38.2%) at 6 months. CFS was 98.0% (95% CI, 92.2%–99.5%) at 3 months and 93.7% (95% CI, 85.2%–97.4%) at 6 months. Median CFS was not reached; only 13.3% of patients underwent radical cystectomy after starting valrubicin. 56 patients (49.6%) experienced ≥1 local adverse reaction; the most common were hematuria and pollakiuria (both 17.7%), micturition urgency (15.9%), and bladder spasm (14.2%). 55 patients (48.7%) used ≥1 concomitant medication for local adverse reactions; the most commonly used were urinary antispasmodics (21.2%), fluoroquinolones (14.2%), and other urologicals (14.2%). Conclusions: In patients with NMIBC treated with intravesical valrubicin, median DFS and PFS were 3.5 and 18.2 months, respectively, and median CFS was not reached as only 13% of patients underwent radical cystectomy. Valrubicin was well tolerated, and most patients received the full course of 6 instillations. Funding: Research and abstract were supported by Endo Pharmaceuticals Inc.

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