Clinical trial NCT06290687: Partial Cystectomy & Extended Pelvic Lymph Node Dissection With SOC Perioperative Systemic Therapy
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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Malignant Neoplasm of Bladder
Muscle Invasive Bladder Carcinoma
Keywords: Partial cystectomy
Pelvic Lymph Node Dissection
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2024-03-04
Enrollment: 40
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a single-center, prospective, phase II trial.
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Recurrence-Free Survival (RFS)
timeFrame: Up to 24 months from date of post-surgery baseline scan
Secondary outcomes:
measure: Presence of Post-operative Complications
timeFrame: At 90 days after surgery
measure: Median Bladder RFS
timeFrame: Up to 24 months from date of post-surgery baseline scan
measure: Median Muscle-Invasive Bladder RFS
timeFrame: Up to 24 months from date of post-surgery baseline scan
measure: Median Bladder-Intact Survival
timeFrame: Up to 24 months from date of post-surgery baseline scan
measure: Median Cancer-Specific Survival
timeFrame: Up to 24 months from date of post-surgery baseline scan
measure: Changes in Genitourinary-specific HRQoL
timeFrame: Up to 24 months from date of post-surgery baseline scan
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Glickman Urological and Kidney Institute, Cleveland Clinic, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic, Case Comprehensive Cancer Center
name: Nima Almassi, MD
role: PRINCIPAL_INVESTIGATOR
References: