Sequential Combination Therapy in Bladder Cancer

NCT03790384 | Unknown Phase 4

• 1 other identifier: 2017-004540-37
• Study Type: interventional
• Target: 140
• Locations: 0 countries
• Sites: N/A

Brief Summary

A consecutive series of patients with High Risk Non-Muscle Invasive Bladder Cancer will be enrolled in several centres. The subjects will be assessed for eligibility at the screening visit (Visit 1) three weeks after Trans-Urethral Resection of the Bladder (TURB) and re-TURB prior to randomization and only subjects who fulfil the inclusion criteria will be included. Patients selected for the study, are centrally randomized (randomization is performed at the Sant'Andrea Hospital) to receive BCG induction treatment according to the standard protocol (an instillation once a week for six weeks) with Immucyst (81 mg Connaught strain BCG). Patients in group two received BCG treatment with the same protocol with a 40 mg mitomycin instillation the day before .

Conditions

Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• Recurrence rate

  To evaluate the effect in term of recurrence rate of sequential combination therapy of Mitomycin and Bacillus Calmette-Guérin versus Bacillus Calmette-Guérin monotherapy in patients with High grade Non-Muscle Invasive Bladder Cancer.through cystoscopy every three months and Uro Tomography Computerized yearly

  2 years

Secondary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  2 years

Study Arms (2)

Bacillus Calmette-Guérin

NO INTERVENTION

Patients receive Bacillus Calmette-Guérin induction treatment according to the standard protocol (an instillation once a week for six weeks) with ImmuCyst (81 mg Connaught strain BCG).

Mytomicin and Bacillus Calmette-Guérin

EXPERIMENTAL

Patients received BCG treatment with the same protocol. Intervention will be a 40 mg mitomycin instillation the day before every single BCG instillation

Drug: Mitomycin

Interventions

Mitomycin DRUG

Patients receive BCG induction treatment according to the standard protocol (an instillation once a week for six weeks) with ImmuCyst (81 mg Connaught strain BCG) with a 40 mg mitomycin instillation the day before .

Also known as: Bacillus Calmette-Guerin

Mytomicin and Bacillus Calmette-Guérin

Eligibility Criteria

• Age: 30 Years+
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with high risk non muscle invasive bladder cancer
• High risk of progression (EORTC risk score \> 6)
• Males
• Signature of Informed Consent
• Ability of consent

You may not qualify if:

• Low Risk Non-Muscle Invasive Bladder Cancer
• Muscle Invasive Bladder Cancer
• Concomitant Urothelial Bladder Cancer in the Upper-Urinary Tract
• Previous bladder or prostate surgery
• Prostate or bladder radiotherapy
• Urinary tract infection
• Chronic urinary retention or indwelling catheters
• Neurological patients
• Previous BCG infections
• Previous or current chemotherapy for other kind of cancers
• Patients older than 75
• WHO performance status 3-4
• Residual tumour on re-TURB

Sponsors & Collaborators

• Azienda Ospedaliera "Sant'Andrea": lead

Related Publications (4)

• Solsona E, Madero R, Chantada V, Fernandez JM, Zabala JA, Portillo JA, Alonso JM, Astobieta A, Unda M, Martinez-Pineiro L, Rabadan M, Ojea A, Rodriguez-Molina J, Beardo P, Muntanola P, Gomez M, Montesinos M, Martinez Pineiro JA; Members of Club Urologico Espanol de Tratamiento Oncologico. Sequential combination of mitomycin C plus bacillus Calmette-Guerin (BCG) is more effective but more toxic than BCG alone in patients with non-muscle-invasive bladder cancer in intermediate- and high-risk patients: final outcome of CUETO 93009, a randomized prospective trial. Eur Urol. 2015 Mar;67(3):508-16. doi: 10.1016/j.eururo.2014.09.026. Epub 2014 Oct 6.

  PMID: 25301758 BACKGROUND

• Cui J, Wang W, Chen S, Chen P, Yang Y, Guo Y, Zhu Y, Chen F, Shi B. Combination of Intravesical Chemotherapy and Bacillus Calmette-Guerin Versus Bacillus Calmette-Guerin Monotherapy in Intermediate- and High-risk Nonmuscle Invasive Bladder Cancer: A Systematic Review and Meta-analysis. Medicine (Baltimore). 2016 Jan;95(3):e2572. doi: 10.1097/MD.0000000000002572.

  PMID: 26817914 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

• Cicione A, Lombardo R, Nacchia A, Franco A, Simone G, Pastore A, Leonardo C, Franco G, Tubaro A, DE Nunzio C. No clinical benefit from sequential combination of mitomycin C plus bacillus Calmette-Guerin (BCG) than BCG alone in the adjuvant treatment of high risk non muscle invasive bladder cancer: result of a planned interim analysis of a prospective randomized trial. Minerva Urol Nephrol. 2024 Aug;76(4):458-466. doi: 10.23736/S2724-6051.24.05777-X. Epub 2024 Jun 5.

  PMID: 38842053 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Mitomycin; BCG Vaccine

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; Tuberculosis Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Andrea Tubaro

  Azienda Ospedaliera "Sant'Andrea"

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrea Tubaro

CONTACT

+390633777712; andrea.tubaro@mac.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The subjects will be assessed for eligibility at the screening visit (Visit 1) three weeks after TURB and re-TURB prior to randomization and only subjects who fulfil the inclusion criteria will be included: patients with a diagnosis of High risk NMIBC: T1 tumor, G3, CIS, or multiple and recurrent and large (\>3 cm) Ta or patients in the last EAU recurrence category (EAU/EORTC recurrence score \>/=10). Patients selected for the study, are centrally randomized (randomization is performed at the Sant'Andrea Hospital) to receive BCG induction treatment according to the standard protocol (an instillation once a week for six weeks) with ImmuCyst (81 mg Connaught strain BCG). Patients in group two received BCG treatment with the same protocol with a 40 mg mitomycin instillation the day before .

Study Record Dates

• First Submitted: December 11, 2018
• First Posted: December 31, 2018
• Study Start: January 15, 2019
• Primary Completion: September 15, 2019
• Study Completion: January 15, 2021
• Last Updated: December 31, 2018

Record last verified: 2018-12