Neoadjuvant Short-term Intensive Chemoresection Versus Standard Adjuvant Intravesical Instillations in NMIBC

NCT03348969 | Completed Phase 4 DMC

• 1 other identifier: DaBlaCa13
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

A randomized controlled trial aiming to investigate neoadjuvant, short-term intensive chemoresection with Mitomycin C compared to standard treatment with TURB and adjuvant intravesical instillation therapy in patients with recurrent non-muscle invasive bladder cancer (NMIBC).

Conditions

Bladder Cancer

Keywords

Mitomycin C; Neoadjuvant

Outcome Measures

Primary Outcomes (1)

• 2-year recurrence rate

  The primary outcome is the number of patients in need for a TURB or tumour fulguration in the first 2 years following randomization. TURBs included as primary endpoint are the initial TURB in the control group, the prospective TURB in the intervention group for patients without complete chemoresection as well as TURB due to recurrence in both study groups. In case a TURB is recommended, but a subject refuses to undergo surgery, the recommended TURB is also registered.

  within 2 years

Secondary Outcomes (4)

• Tumour response rate

  6 months after complete enrollment

• 5-year recurrence rate

  within 5 years

• Adverse events

  6 months after complete enrollment

• Biomarkers

  within 2 years

Study Arms (2)

Intervention

EXPERIMENTAL

Neoadjuvant Mitomycin C

Drug: Mitomycin c

Control

ACTIVE COMPARATOR

Adjuvant Mitomycin C

Drug: Mitomycin c

Interventions

Mitomycin c DRUG

Neoadjuvant Mitomycin C

Also known as: Mitomycin "Medac"

Control; Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Known history of urothelial non-invasive Ta-tumour low-grade or high-grade.
• ≥18 years old
• Mentally healthy individual
• The ability to understand Danish orally and in writing

You may not qualify if:

• Known history of invasive tumour of the bladder (T1+)
• Known history of CIS of the bladder
• Previous BCG-treatment within the last 24 months
• Previous Mitomycin C-treatment (except single-shot postoperative instillation)
• Known allergy or intolerance to Mitomycin C
• Solid tumour with suspicions of invasion
• Single tumour of more than 2 cm in diameter
• Suspicion of CIS (positive cytology with high-grade neoplastic cells combined with suspicious cystoscopy for flat lesions).
• Small bladder volume (less than 100 ml) or incontinence
• Acute cystitis
• Pregnancy or breast-feeding
• Not willing to use secure contraception with regard to men with partners and premenopausal women

Sponsors & Collaborators

• Jørgen Bjerggaard Jensen: lead

Study Sites (1)

Aarhus University Hospital

Aarhus, 8200, Denmark

Location

Related Publications (15)

• Herr H. Re: Marko Babjuk, Andreas Bohle, Maximilian Burger, et al. EAU Guidelines on Non-muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016. Eur Urol 2017;71:447-61. Eur Urol. 2017 Jun;71(6):e171-e172. doi: 10.1016/j.eururo.2016.11.030. Epub 2016 Dec 12. No abstract available.

  PMID: 27979427 BACKGROUND

• Maffezzini M. Re: Richard J. Sylvester, Adrian P.M. van der Meijden, Willem Oosterlinck, J. Alfred Witjes, Christian Bouffioux, Louis Denis and Donald W.W. Newling. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol 2006;49:466-77. Eur Urol. 2006 Sep;50(3):623-4; author reply 624-5. doi: 10.1016/j.eururo.2006.04.005. Epub 2006 May 4. No abstract available.

  PMID: 16707208 BACKGROUND

• Kaasinen E, Wijkstrom H, Rintala E, Mestad O, Jahnson S, Malmstrom PU. Seventeen-year follow-up of the prospective randomized Nordic CIS study: BCG monotherapy versus alternating therapy with mitomycin C and BCG in patients with carcinoma in situ of the urinary bladder. Scand J Urol. 2016 Oct;50(5):360-8. doi: 10.1080/21681805.2016.1210672. Epub 2016 Aug 15.

  PMID: 27603424 BACKGROUND

• Lamm DL. Preventing progression and improving survival with BCG maintenance. Eur Urol. 2000;37 Suppl 1:9-15. doi: 10.1159/000052376.

  PMID: 10575266 BACKGROUND

• Shelley MD, Wilt TJ, Court J, Coles B, Kynaston H, Mason MD. Intravesical bacillus Calmette-Guerin is superior to mitomycin C in reducing tumour recurrence in high-risk superficial bladder cancer: a meta-analysis of randomized trials. BJU Int. 2004 Mar;93(4):485-90. doi: 10.1111/j.1464-410x.2003.04655.x.

  PMID: 15008714 BACKGROUND

• Shida K, Shimasaki J, Takahashi H, Kurihara H, Sato J. [Therapy and prognosis of bladder tumors--result of injection of mitomycin C into the bladder]. Gan No Rinsho. 1970 Jul;16(7):737-44. No abstract available. Japanese.

  PMID: 5465489 BACKGROUND

• Colombo R, Rocchini L, Suardi N, Benigni F, Colciago G, Bettiga A, Pellucchi F, Maccagnano C, Briganti A, Salonia A, Rigatti P, Montorsi F. Neoadjuvant short-term intensive intravesical mitomycin C regimen compared with weekly schedule for low-grade recurrent non-muscle-invasive bladder cancer: preliminary results of a randomised phase 2 study. Eur Urol. 2012 Nov;62(5):797-802. doi: 10.1016/j.eururo.2012.05.032. Epub 2012 May 18.

  PMID: 22633362 BACKGROUND

• Sousa A, Inman BA, Pineiro I, Monserrat V, Perez A, Aparici V, Gomez I, Neira P, Uribarri C. A clinical trial of neoadjuvant hyperthermic intravesical chemotherapy (HIVEC) for treating intermediate and high-risk non-muscle invasive bladder cancer. Int J Hyperthermia. 2014 May;30(3):166-70. doi: 10.3109/02656736.2014.900194. Epub 2014 Apr 3.

  PMID: 24697672 BACKGROUND

• Miyata Y, Sakai H. Predictive Markers for the Recurrence of Nonmuscle Invasive Bladder Cancer Treated with Intravesical Therapy. Dis Markers. 2015;2015:857416. doi: 10.1155/2015/857416. Epub 2015 Nov 23.

  PMID: 26681820 BACKGROUND

• Seo HK, Cho KS, Chung J, Joung JY, Park WS, Chung MK, Lee KH. Prognostic value of p53 and Ki-67 expression in intermediate-risk patients with nonmuscle-invasive bladder cancer receiving adjuvant intravesical mitomycin C therapy. Urology. 2010 Aug;76(2):512.e1-7. doi: 10.1016/j.urology.2010.04.040. Epub 2010 Jun 26.

  PMID: 20579709 BACKGROUND

• Chen JX, Deng N, Chen X, Chen LW, Qiu SP, Li XF, Li JP. A novel molecular grading model: combination of Ki67 and VEGF in predicting tumor recurrence and progression in non-invasive urothelial bladder cancer. Asian Pac J Cancer Prev. 2012;13(5):2229-34. doi: 10.7314/apjcp.2012.13.5.2229.

  PMID: 22901199 BACKGROUND

• Karam JA, Lotan Y, Ashfaq R, Sagalowsky AI, Shariat SF. Survivin expression in patients with non-muscle-invasive urothelial cell carcinoma of the bladder. Urology. 2007 Sep;70(3):482-6. doi: 10.1016/j.urology.2007.05.009.

  PMID: 17905101 BACKGROUND

• Bracci L, Schiavoni G, Sistigu A, Belardelli F. Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer. Cell Death Differ. 2014 Jan;21(1):15-25. doi: 10.1038/cdd.2013.67. Epub 2013 Jun 21.

  PMID: 23787994 BACKGROUND

• Hugo W, Zaretsky JM, Sun L, Song C, Moreno BH, Hu-Lieskovan S, Berent-Maoz B, Pang J, Chmielowski B, Cherry G, Seja E, Lomeli S, Kong X, Kelley MC, Sosman JA, Johnson DB, Ribas A, Lo RS. Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma. Cell. 2017 Jan 26;168(3):542. doi: 10.1016/j.cell.2017.01.010. No abstract available.

  PMID: 28129544 BACKGROUND

• Lindgren MS, Hansen E, Azawi N, Nielsen AM, Dyrskjot L, Jensen JB. DaBlaCa-13 Study: Oncological Outcome of Short-Term, Intensive Chemoresection With Mitomycin in Nonmuscle Invasive Bladder Cancer: Primary Outcome of a Randomized Controlled Trial. J Clin Oncol. 2023 Jan 10;41(2):206-211. doi: 10.1200/JCO.22.00470. Epub 2022 Oct 12.

  PMID: 36223555 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Mitomycin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Jørgen Bjerggaard Jensen, MD

  Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, MD

Model Details: Randomized Clinical Trial

Study Record Dates

• First Submitted: November 13, 2017
• First Posted: November 21, 2017
• Study Start: November 1, 2017
• Primary Completion: June 11, 2019
• Study Completion: December 31, 2025
• Last Updated: March 3, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)