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

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)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Muscle Invasive Bladder Carcinoma; Malignant Neoplasm of Bladder
• Intervention / Treatment: Drug: Neoadjuvant Chemotherapy; Procedure: Partial cystectomy with Extended pelvic lymph node dissection; Drug: Adjuvant systemic therapy

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Nima Almassi, MD; Phone Number: (216) 444-1825; Email: almassn2@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Glickman Urological and Kidney Institute, Cleveland Clinic, Case Comprehensive Cancer Center
      • Contact: Nima Almassi, MD; Phone Number: 216-444-1825; Email: almassn2@ccf.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cisplatin Eligible Participants; Participants who are deemed eligible for cisplatin-based NAC will undergo: Standard of care neoadjuvant systemic therapy (currently cisplatin-based chemotherapy in cisplatin-eligible participants); Partial cystectomy with extended pelvic lymph node dissection; Standard of care adjuvant systemic therapy in eligible patients	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.
Experimental: Cisplatin Ineligible Participants; Participants who are deemed ineligible for cisplatin-based NAC will undergo: Partial cystectomy with extended pelvic lymph node dissection; Standard of care adjuvant systemic therapy in eligible participants	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Investigators: Principal Investigator: Nima Almassi, MD, Cleveland Clinic, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): January 29, 2026
• Study Completion (Estimated): January 29, 2027

Study Registration Dates

• First Submitted: February 26, 2024
• First Submitted That Met QC Criteria: February 26, 2024
• First Posted (Actual): March 4, 2024

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Pelvic Lymph Node Dissection; Partial cystectomy
• Additional Relevant MeSH Terms: Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Neoplasms; Urinary Bladder Neoplasms
• Other Study ID Numbers: CASE5824

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No