Hyperthermic Intravesical Chemotherapy (HIVEC) in BCG-Non-Responsive High-Grade NMIBC Patients

NCT07231809 | Not Yet Recruiting

• 1 other identifier: SMG-Bladder 01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase II, prospective, single-arm, open-label clinical study evaluating hyperthermic intravesical chemotherapy (HIVEC) with Mitomycin C in patients with high-grade, non-muscle-invasive bladder cancer (NMIBC) who are BCG-non-responsive or BCG-intolerant and are ineligible for, or refuse, radical cystectomy. Mitomycin C is an approved medicinal product used within routine clinical practice and administered with a CE-marked recirculation device (BRS Combat system) that maintains the solution at approximately 43°C for 60 minutes. The treatment schedule consists of 6 weekly induction instillations followed by 9 monthly maintenance instillations. The co-primary objectives are to describe the safety and toxicity profile of HIVEC, including treatment discontinuations due to procedure-related toxicity, and to estimate the 12-month recurrence-free survival (12moRFS). Secondary objectives include characterizing patterns of non-muscle-invasive and muscle-invasive recurrences, bladder cancer-specific survival, overall survival, and quality of life. Approximately 50 patients will be enrolled in this single-center pilot study to generate exploratory safety and efficacy data in this high-risk population and to support the design of future randomized trials

Conditions

Non Muscle Invasive Bladder Cancer; Bladder Cancer; Carcinoma in Situ of Bladder; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell, Bladder

Keywords

HIVEC; Hyperthermic Intravesical Chemotherapy; Mitomycin C; BRS Combat System; Bladder Tumor Recurrence; High-Grade Bladder Cancer

Outcome Measures

Primary Outcomes (2)

• Treatment-Related Adverse Events (AEs)

  Incidence, type, timing, and severity of adverse events graded according to NCI CTCAE v5.0. Includes local and systemic toxicities related to hyperthermic intravesical chemotherapy and the proportion of patients who discontinue treatment due to toxicity.

  Up to 12 months

• 12-Month Recurrence-Free Survival (RFS)

  Proportion of patients who remain free from histologically confirmed recurrence of non-muscle-invasive bladder cancer (Ta, T1, or CIS) at 12 months from initiation of HIVEC treatment. Recurrence is defined per standard cystoscopic and histological criteria.

  12 months after completion of the HIVEC treatment schedule

Secondary Outcomes (5)

• Rate of non-muscle-invasive (Ta-T1) bladder cancer recurrences

  Up to 12 months

• Rate of muscle-invasive (≥T2) recurrences

  Up to 12 months

• Cancer-specific survival

  up to 12 months

• Overall Survival (OS)

  Up to 12 months

• Quality of Life (QoL)

  Up to 12 months

Study Arms (1)

HIVEC Treatment Arm

EXPERIMENTAL

Participants will receive Hyperthermic Intravesical Chemotherapy (HIVEC) with Mitomycin C according to the study protocol (induction + maintenance schedule). Mitomycin C is an approved medicinal product used within routine clinical practice. HIVEC is performed using a CE-marked recirculation system that maintains the solution at a controlled therapeutic temperature.

Procedure: Hyperthermic Intravesical Chemotherapy (HIVEC)

Interventions

Hyperthermic Intravesical Chemotherapy (HIVEC) PROCEDURE

Intravesical administration of Mitomycin C heated to approximately 43°C using a CE-marked recirculation system (BRS Combat device). Mitomycin C is supplied by the treating hospital as part of routine clinical practice. The procedure consists of 6 weekly instillations followed by 9 monthly instillations.

Also known as: HIVEC System, BRS Combat

HIVEC Treatment Arm

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years.
• Histologically confirmed high-grade non-muscle-invasive bladder cancer (NMIBC), including Ta, T1, and/or carcinoma in situ (CIS).
• BCG-unresponsive or BCG-intolerant disease according to international definitions (persistent or recurrent high-grade NMIBC after adequate BCG therapy).
• Patient is ineligible for, or refuses, radical cystectomy.
• Candidate for hyperthermic intravesical chemotherapy (HIVEC) according to clinical judgment.
• ECOG Performance Status 0-2.
• Adequate organ function according to institutional standards.
• Ability and willingness to comply with study procedures and follow-up schedule.
• Written informed consent obtained.

You may not qualify if:

• Muscle-invasive bladder cancer (≥ T2) or metastatic disease.
• Active urinary tract infection at baseline.
• Previous treatment with HIVEC or other intravesical hyperthermia systems.
• Known hypersensitivity to Mitomycin C or contraindications to intravesical chemotherapy.
• Active uncontrolled bleeding or gross hematuria preventing intravesical instillation.
• Upper urinary tract urothelial carcinoma.
• Pregnant or breastfeeding women.
• Any medical or psychological condition that, in the investigator's judgment, could interfere with study participation or compromise patient safety.

Sponsors & Collaborators

• AC.TA. S.r.l.: lead

Study Sites (1)

P.O. "Santa Maria delle Grazie" - ASL Napoli 2 Nord

Pozzuoli, 80078, Italy

Location

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms; Carcinoma

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Gaetano Facchini, MD

  P.O. "Santa Maria delle Grazie" - ASL Napoli 2 Nord

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gaetano Facchini, MD

CONTACT

+3908118844043; gaetano.facchini@aslnapoli2nord.it

Alessandra Marabese, Perfusionist

CONTACT

+393388355145; alessandra.marabese@actagroup.eu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Prospective, single-arm, non-randomized, Phase II therapeutic study evaluating hyperthermic intravesical chemotherapy.

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: November 17, 2025
• Study Start (Estimated): October 15, 2026
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): May 31, 2028
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

IT (1)