Partial Cystectomy & Extended Pelvic Lymph Node Dissection With SOC Perioperative Systemic Therapy

Muscle Invasive Bladder Carcinoma Clinical Trial

Official title:

Phase II Trial on the Safety and Efficacy of Partial Cystectomy and Extended Pelvic Lymph Node Dissection With Standard of Care Perioperative Systemic Therapy in the Management of Muscle-Invasive Bladder Cancer (PRESERVE Trial)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06290687
• Other study ID #: CASE5824
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: August 2024
• Est. completion date: January 29, 2027

Study information

• Verified date: March 2024
• Source: Case Comprehensive Cancer Center
• Contact: Nima Almassi, MD
• Phone: (216) 444-1825
• Email: almassn2[@]ccf.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to determine if a partial cystectomy with extended pelvic lymph node removal will be effective at treating Muscle-Invasive Bladder Cancer instead of a complete cystectomy with extended pelvic lymph node removal. This clinical trial aims to determine the safety and oncologic efficacy of the intervention, and to examine patient-reported quality of life outcomes in participants. Participants will receive the standard pre-surgery treatment for approximately 4 to 6 weeks. After the pre-surgery treatment is completed, participants will undergo a partial cystectomy with extended pelvic lymph node dissection. After surgery, participants will receive adjuvant systemic therapy.

Description:

Radical cystectomy (surgical removal of the bladder) with pelvic lymph node dissection and urinary diversion, with neoadjuvant chemotherapy in eligible participants, is the standard of care in participants with muscle-invasive bladder cancer (MIBC). While this has demonstrated efficacy in the treatment of MIBC, it has risk of perioperative morbidity and impacts quality of life. Partial cystectomy (surgical removal of a portion of the bladder) is one option for bladder-sparing treatment of select bladder cancer participants and is included in the National Comprehensive Cancer Network bladder cancer treatment guidelines. This treatment has the advantage of less invasive treatment with a lower risk of surgical complication and better health-related quality of life (HRQOL) while providing pathologic staging, however there are limited data on outcomes with this treatment, especially patient-reported HRQOL outcomes. Additionally, much of the existing literature on efficacy of this treatment predates the use of advanced imaging in preoperative staging and advances in surgical technique including use of minimally-invasive surgical approaches and enhanced-recovery post-operative care paths. Given these limitations in the existing literature, the aim of this clinical trial is to examine the safety and efficacy and HRQOL outcomes of partial cystectomy with extended pelvic lymph node dissection, with standard of care perioperative systemic therapy in eligible participants.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: January 29, 2027
• Est. primary completion date: January 29, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

• Subjects must have histologically confirmed urothelial carcinoma of the bladder, clinical stage T2-3N0M0. Micropapillary, glandular, squamous, and sarcomatoid histologic variants of urothelial carcinoma are allowed.

• Subjects must have unifocal or limited multifocal disease amenable to complete surgical resection with partial cystectomy, as judged by the treating urologic oncologist.

• Age >18 years. Because of the rarity of this disease and limited data on treatment efficacy in subjects 18 years of age, children are excluded from this study.

• Performance status - Karnofsky Performance Status =70 or Eastern Cooperative Oncology Group (ECOG) performance status Grade 0 or 1.

• Subjects must have normal organ and marrow function as defined below:

• Total bilirubin within normal limits

• AST (SGOT) = 2.5 X institutional upper limit of normal

• ALT (SGPT) = 2.5 X institutional upper limit of normal

• Bone marrow:

• Absolute neutrophil count (ANC) = 1,500/mm3

• Platelet count = 80,000/mm3, Hemoglobin = 9.0 g/dL

• Subjects must have the ability to understand and the willingness to sign a written informed consent document.

• Subjects must have tumor less than or equal to 5 cm in largest dimension as assessed radiographically.

• Treatment naive for MIBC.

Exclusion Criteria:

• Presence of hydronephrosis.

• Presence of multifocal disease that is not amenable to complete resection with partial cystectomy.

• Presence of distant carcinoma in situ.

• Presence of clinical N+ or M+ disease.

• Presence of cT4+ disease.

• Non-urothelial histology.

• Concurrent upper tract (ureter or renal pelvis) or urethral urothelial carcinoma.

• Subjects who are not surgical candidates due to competing medical comorbidities or who refuse surgical treatment.

• Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.

Related Conditions & MeSH terms

• Muscle Invasive Bladder Carcinoma
• Neoplasms
• Urinary Bladder Neoplasms

Intervention

Drug:
• Neoadjuvant Chemotherapy
Standard of care neoadjuvant systemic therapy is currently cisplatin-based chemotherapy in cisplatin-eligible participants. Participants will start treatment within 60 days of Transurethral Resection of Bladder Tumor. Regimens may include: Cisplatin - Gemcitabine (Gem/Cis) Dose Dense Methotrexate - Vinblastine - Adriamycin - Cisplatin (MVAC)

Procedure:
• Partial cystectomy with Extended pelvic lymph node dissection
Partial cystectomy will then be performed using the surgical technique at the discretion of the treating Urologic Oncologist. Extended pelvic lymphadenectomy will then be performed at the discretion of the treating Urologic Oncologist. Surgery will be performed within 60 days of Transurethral Resection of Bladder Tumor for Cisplatin-ineligible participants. Surgery will be performed within 60 days of completing neoadjuvant chemotherapy for Cisplatin-eligible participants.

Drug:
• Adjuvant systemic therapy
Standard of care adjuvant systemic therapy in eligible participants. The choice of adjuvant systemic therapy will be left to the discretion of the treating Medical Oncologist but must fall within the SOC as outlined in NCCN guidelines.

Locations

Country	Name	City	State
United States	Glickman Urological and Kidney Institute, Cleveland Clinic, Case Comprehensive Cancer Center	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Case Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence-Free Survival (RFS)	Recurrence-Free Survival (RFS) is defined as the time from post-surgery baseline scan (revealing no recurrent/metastatic disease) until the first occurrence of either local or distant recurrence as assessed by CT or MRI and/or biopsy. The primary outcome of distant RFS will be assessed via Kaplan-Meier analysis	Up to 24 months from date of post-surgery baseline scan
Secondary	Presence of Post-operative Complications	The Clavien-Dindo classification will measure post-operative complications. The Clavien-Dindo Classification of Post-operative Complications is a tool to assess complications following surgical treatment. This tool ranks complications on a scale of seven levels, with level 1 being the least complicated and 7 being the worst complication resulting in death. The average classification at 90 days will be assessed and reported.	At 90 days after surgery
Secondary	Median Bladder RFS	The median duration of bladder recurrence-free survival at 2 years.	Up to 24 months from date of post-surgery baseline scan
Secondary	Median Muscle-Invasive Bladder RFS	The median duration of muscle-invasive bladder recurrence-free survival at 2 years.	Up to 24 months from date of post-surgery baseline scan
Secondary	Median Bladder-Intact Survival	The median duration of bladder-intact survival at 2 years.	Up to 24 months from date of post-surgery baseline scan
Secondary	Median Cancer-Specific Survival	The median duration of cancer-specific survival at 2 years.	Up to 24 months from date of post-surgery baseline scan
Secondary	Changes in Genitourinary-specific HRQoL	The mean changes in Genitourinary-specific HRQoL will be reported. The HRQoL survey is composed of five functional scales (physical, role, emotional, cognitive, and social functioning), three symptom scales (fatigue, nausea and vomiting, pain), a global health status/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The scales and single-item measures range from 0 - 100, with higher values representing a higher response level.	Up to 24 months from date of post-surgery baseline scan