NCT05776758

Brief Summary

This prospective randomized controlled trial (RCT) is designed to provide high level evidence describing the non-inferiority of radical cystectomy (RC) alone versus neoadjuvant chemotherapy (NAC) plus RC on survival outcomes of patients with a diagnostic transurethral resection of bladder tumor (TURBt) of non-metastatic muscle invasive bladder cancer (MIBC) (T2-T4 N0 M0) and non-radiologic or endoscopic residual tumor after a maximal TURBt (cT0). Our hypothesis is that performing NAC in the absence of residual disease, after a maximal TURBt, has no survival benefit over performing an early cystectomy. Since no downstaging could be achieved in patients with no residual tumor into the bladder, the benefits of neoadjuvant chemotherapy in this setting could be not significant and it might turn into unnecessary toxicity and a substantial delay to surgical treatment.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
236

participants targeted

Target at P50-P75 for phase_3

Timeline
8mo left

Started Nov 2024

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress69%
Nov 2024Jan 2027

First Submitted

Initial submission to the registry

January 31, 2023

Completed
2 months until next milestone

First Posted

Study publicly available on registry

March 20, 2023

Completed
1.7 years until next milestone

Study Start

First participant enrolled

November 29, 2024

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2026

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2027

Expected
Last Updated

April 16, 2025

Status Verified

April 1, 2025

Enrollment Period

1.1 years

First QC Date

January 31, 2023

Last Update Submit

April 11, 2025

Conditions

Muscle-Invasive Bladder CarcinomaChemotherapy EffectSurgery

Keywords

Bladder cancerMuscle-invasive bladder cancerRadical cystectomySurvival outcomes

Outcome Measures

Primary Outcomes (1)

  • To demonstrate the non-inferiority of radical cystectomy (RC) alone versus neoadjuvant chemotherapy plus RC on 2 years Overall Survival (OS) rates, defined as the length of time from surgery until death from any cause.

    Overall Survival rates

    2 years

Secondary Outcomes (7)

  • To compare disease free survival (DFS) rates, defined as the length of time from surgery to local disease recurrence

    6 months, 1 year, 2 years

  • To evaluate metastasis free survival (MFS) rates, defined as the length of time from surgery to metastasis recurrence.

    6 months, 1 year, 2 years

  • To evaluate recurrence free survival (RFS), rates defined as the length of time from surgery to disease recurrence.

    6 months, 1 year, 2 years

  • To evaluate impact of NAC on perioperative complications rate (described accordingly to Clavien Dindo classification into minor o major complications)

    Within hospital stay

  • To evaluate impact of NAC on postoperative complications rate described accordingly to Clavien Dindo classification into minor o major complications)

    30 days, 90 days and 180 days

  • +2 more secondary outcomes

Study Arms (2)

NAC+RC

EXPERIMENTAL

cisplatin-based neoadjuvant chemotherapy plus radical cystectomy

Drug: cisplatin based neoadjuvant chemotherapyProcedure: Radical cystectomy alone

RC alone

ACTIVE COMPARATOR

radical cystectomy alone

Procedure: Radical cystectomy alone

Interventions

cisplatin based neoadjuvant chemotherapyDRUG

cisplatin based neoadjuvant chemotherapy

NAC+RC
Radical cystectomy alonePROCEDURE

RC alone

NAC+RCRC alone

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • diagnostic TURBt with cT2-4, cN0, cM0;
  • non-radiologic or endoscopic residual tumor after a maximal TURBt (cT0);
  • patients eligible to curative intent, candidate to surgical treatment and/or NAC (all patients must meet all the criteria required to be able to undergo RC and/or NAC);
  • ≥ 18 yrs old;
  • compliants patients able to follow the study protocol and fill in EORTC quality of life questionnaires;
  • patients able to provide a written informed consent for the trial

You may not qualify if:

  • anaesthesiologic contraindications to surgery;
  • palliative intent;
  • patients ineligible for cisplatin-combination chemotherapy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Riccardo Mastroianni

Rome, 00144, Italy

Location

Related Publications (11)

  • Stein JP, Lieskovsky G, Cote R, Groshen S, Feng AC, Boyd S, Skinner E, Bochner B, Thangathurai D, Mikhail M, Raghavan D, Skinner DG. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol. 2001 Feb 1;19(3):666-75. doi: 10.1200/JCO.2001.19.3.666.

    PMID: 11157016RESULT

  • Stein JP, Skinner DG. Radical cystectomy for invasive bladder cancer: long-term results of a standard procedure. World J Urol. 2006 Aug;24(3):296-304. doi: 10.1007/s00345-006-0061-7. Epub 2006 Mar 4.

    PMID: 16518661RESULT

  • Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, deVere White RW, Sarosdy MF, Wood DP Jr, Raghavan D, Crawford ED. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003 Aug 28;349(9):859-66. doi: 10.1056/NEJMoa022148.

    PMID: 12944571RESULT

  • Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists. Lancet. 1999 Aug 14;354(9178):533-40.

    PMID: 10470696RESULT

  • International Collaboration of Trialists; Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group); European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group; Australian Bladder Cancer Study Group; National Cancer Institute of Canada Clinical Trials Group; Finnbladder; Norwegian Bladder Cancer Study Group; Club Urologico Espanol de Tratamiento Oncologico Group; Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol. 2011 Jun 1;29(16):2171-7. doi: 10.1200/JCO.2010.32.3139. Epub 2011 Apr 18.

    PMID: 21502557RESULT

  • Takata R, Katagiri T, Kanehira M, Tsunoda T, Shuin T, Miki T, Namiki M, Kohri K, Matsushita Y, Fujioka T, Nakamura Y. Predicting response to methotrexate, vinblastine, doxorubicin, and cisplatin neoadjuvant chemotherapy for bladder cancers through genome-wide gene expression profiling. Clin Cancer Res. 2005 Apr 1;11(7):2625-36. doi: 10.1158/1078-0432.CCR-04-1988.

    PMID: 15814643RESULT

  • Takata R, Katagiri T, Kanehira M, Shuin T, Miki T, Namiki M, Kohri K, Tsunoda T, Fujioka T, Nakamura Y. Validation study of the prediction system for clinical response of M-VAC neoadjuvant chemotherapy. Cancer Sci. 2007 Jan;98(1):113-7. doi: 10.1111/j.1349-7006.2006.00366.x.

    PMID: 17116130RESULT

  • Driscoll JJ, Rixe O. Overall survival: still the gold standard: why overall survival remains the definitive end point in cancer clinical trials. Cancer J. 2009 Sep-Oct;15(5):401-5. doi: 10.1097/PPO.0b013e3181bdc2e0.

    PMID: 19826360RESULT

  • Kim HS, Jeong CW, Kwak C, Kim HH, Ku JH. Disease-Free Survival at 2 and 3 Years is a Significant Early Surrogate Marker Predicting the 5-Year Overall Survival in Patients Treated with Radical Cystectomy for Urothelial Carcinoma of the Bladder: External Evaluation and Validation in a Cohort of Korean Patients. Front Oncol. 2015 Oct 29;5:246. doi: 10.3389/fonc.2015.00246. eCollection 2015.

    PMID: 26579498RESULT

  • Witjes JA, Bruins HM, Cathomas R, Comperat EM, Cowan NC, Gakis G, Hernandez V, Linares Espinos E, Lorch A, Neuzillet Y, Rouanne M, Thalmann GN, Veskimae E, Ribal MJ, van der Heijden AG. European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2020 Guidelines. Eur Urol. 2021 Jan;79(1):82-104. doi: 10.1016/j.eururo.2020.03.055. Epub 2020 Apr 29.

    PMID: 32360052RESULT

  • Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. doi: 10.1097/01.sla.0000133083.54934.ae.

    PMID: 15273542RESULT

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Cystectomy

Condition Hierarchy (Ancestors)

Urologic NeoplasmsUrogenital NeoplasmsNeoplasms by SiteNeoplasmsFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesUrinary Bladder DiseasesUrologic DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

Urologic Surgical ProceduresUrogenital Surgical ProceduresSurgical Procedures, Operative

Study Officials

  • Giuseppe Simone, MD

    IRCCS "Regina Elena" National Cancer Institute

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD, Chief of Urology

Study Record Dates

First Submitted

January 31, 2023

First Posted

March 20, 2023

Study Start

November 29, 2024

Primary Completion

January 1, 2026

Study Completion (Estimated)

January 1, 2027

Last Updated

April 16, 2025

Record last verified: 2025-04

Data Sharing

IPD Sharing
Will not share

Locations

IT(1)