Chemoablation for Low-Grade Bladder Cancer

Official title

COBRA - Chemoablation for Low Grade Bladder Cancer: A Single Arm, Prospective, Open-label, Investigator-initiated Phase 2 Study

Overview

The goal of this single arm, prospective, open-label, investigator-initiated Phase 2 clinical trial is to evaluate the efficacy of intravesical chemoablation in patients with low grade bladder cancer.

Detailed description

In this study, patients with histologically confirmed Ta low-grade bladder cancer will undergo chemoablation with gemcitabine (six weekly instillations). The study aims to evaluate the efficacy, safety, and tolerability of chemoablation.

Interventions

• Drug Gemcitabine
  Intravesical installation

Primary outcome measures

• Clinical complete response (cCR) [Time frame: From the end of treatment (EOT) visit to the follow-up visits (1 and 3 months post-treatment).]

Secondary outcome measures (3)

• Pathological complete response (pCR) [Time frame: From the end of treatment visit (EOT) to the follow-up visits (1 and 3 months post-treatment).]
• Patient-reported Outcomes based on EORTC QLQ-NMIBC24 [Time frame: Will be measured weekly during treatment period, at the end of treatment visit and follow-up visits (1 and 3 months post-treatment).]
• Patient-reported Outcomes based on EORTC QLQ-C30 [Time frame: Will be measured weekly during treatment period, at the end of treatment visit and follow-up visits (1 and 3 months post-treatment).]

Eligibility criteria

Inclusion criteria

• Male/female participants who are at least 18 years of age on the day of providing documented informed consent will be enrolled in this study
• Diagnosis of a recurrent tumor and a history of TaLG BCa or diagnosis of primary TaLG BCa histologically confirmed by cold cup biopsy at screening or within 8 weeks before screening
• On screening cystoscopy: Diameter of the largest lesion ≤15mm
• Number of lesions ≤5
• Cystoscopy with bladder diagram including number, site, size and appearance of the tumors with photo documentation
• Patient who has recurrence of and not other than TaLG NMIBC (low or intermediate EAU risk)
• NMIBC requiring treatment with transurethral resection of bladder tumors (TURBT)
• Negative voiding cytology for high grade (HG) disease within 8 weeks before Screening
• No lymph node metastasis or distant metastasis
• Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment
• Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment. Female patients of childbearing potential must use adequate contraception during study period
• Willing and able to provide informed consent

Exclusion criteria

• Tumors that clinicians suspect to be HG
• Positive HG cytology according to Paris criteria
• Diameter of tumor >15 mm
• Number of lesions >5
• Any previous intravesical therapy within 1 year
• Previous HG NMIBC (within the last 3 years). It is allowed to include patients who had history of HG disease longer than 3 years ago.
• Past or current muscle invasive bladder cancer (i.e., T2, T3, T4) or metastatic UC
• History of upper tract urothelial carcinoma (UTUC)
• Clinically significant urethral stricture that would preclude passage of a urethral catheter
• History of neurogenic bladder; active urinary retention; any other condition that would prohibit normal voiding
• Evidence of active urinary tract infection (UTI) that in the Investigator's opinion cannot be treated and resolved prior to biopsy and/or administration of study treatment
• Patient refused to participate
• Known positive human immunodeficiency virus (HIV) test.
• Female patients who are pregnant/breastfeeding.
• Female patients of childbearing potential not using adequate contraception.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Austria · 1 center

• Department of Urology, Medical University of Vienna — Vienna

Publications

• Brausi MA, Gontero P, Altieri V, Colombo R, Conti I, Bono AV. Can gemcitabine instillation ablate solitary low-risk non-muscle-invasive bladder cancer? Results of a phase II marker lesion study. Urol Int. 2011;87(4):470-4. doi: 10.1159/000331727. Epub 2011 Nov 11. PMID 22086229
• Gardmark T, Carringer M, Beckman E, Malmstrom PU; Members of the Intravesical Gemcitabine Study Group. Randomized phase II marker lesion study evaluating effect of scheduling on response to intravesical gemcitabine in recurrent Stage Ta urothelial cell carcinoma of the bladder. Urology. 2005 Sep;66(3):527-30. doi: 10.1016/j.urology.2005.03.084. PMID 16140071
• Maffezzini M, Campodonico F, Canepa G, Capponi G, Fontana V. Short-schedule intravesical gemcitabine with ablative intent in recurrent Ta-T1, G1-G2, low- or intermediate-risk, transitional cell carcinoma of the bladder. Eur Urol. 2007 Apr;51(4):956-61. doi: 10.1016/j.eururo.2006.08.038. Epub 2006 Sep 20. PMID 17027141
• Campodonico F, Canepa G, Capponi G, Bozzo L, Maffezzini M. Intravesical gemcitabine in recurrent superficial bladder carcinoma: preliminary results on ablative efficacy and tolerability. Anticancer Res. 2005 May-Jun;25(3c):2381-4. PMID 16080464
• Serretta V, Galuffo A, Pavone C, Allegro R, Pavone-MacAluso M. Gemcitabine in intravesical treatment of Ta-T1 transitional cell carcinoma of bladder: Phase I-II study on marker lesions. Urology. 2005 Jan;65(1):65-9. doi: 10.1016/j.urology.2004.08.027. PMID 15667865
• Gontero P, Casetta G, Maso G, Sogni F, Pretti G, Zitella A, Frea B, Tizzani A. Phase II study to investigate the ablative efficacy of intravesical administration of gemcitabine in intermediate-risk superficial bladder cancer (SBC). Eur Urol. 2004 Sep;46(3):339-43. doi: 10.1016/j.eururo.2004.05.001. PMID 15306105

Identifiers

NCT: NCT07019220 · COBRA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗