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

Phase 2
Not yet recruiting
Conditions
Malignant Neoplasm of Bladder
Muscle Invasive Bladder Carcinoma
Interventions
Drug: Neoadjuvant Chemotherapy
Procedure: Partial cystectomy with Extended pelvic lymph node dissection
Drug: Adjuvant systemic therapy
Registration Number
NCT06290687
Lead Sponsor
Case Comprehensive Cancer Center
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.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
40
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cisplatin Eligible ParticipantsNeoadjuvant ChemotherapyParticipants 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
Cisplatin Eligible ParticipantsAdjuvant systemic therapyParticipants 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
Cisplatin Ineligible ParticipantsPartial cystectomy with Extended pelvic lymph node dissectionParticipants 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
Cisplatin Eligible ParticipantsPartial cystectomy with Extended pelvic lymph node dissectionParticipants 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
Cisplatin Ineligible ParticipantsAdjuvant systemic therapyParticipants 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
Primary Outcome Measures
NameTimeMethod
Recurrence-Free Survival (RFS)Up to 24 months from date of post-surgery baseline scan

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

Secondary Outcome Measures
NameTimeMethod
Median Cancer-Specific SurvivalUp to 24 months from date of post-surgery baseline scan

The median duration of cancer-specific survival at 2 years.

Median Bladder RFSUp to 24 months from date of post-surgery baseline scan

The median duration of bladder recurrence-free survival at 2 years.

Presence of Post-operative ComplicationsAt 90 days after surgery

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.

Median Muscle-Invasive Bladder RFSUp to 24 months from date of post-surgery baseline scan

The median duration of muscle-invasive bladder recurrence-free survival at 2 years.

Median Bladder-Intact SurvivalUp to 24 months from date of post-surgery baseline scan

The median duration of bladder-intact survival at 2 years.

Changes in Genitourinary-specific HRQoLUp to 24 months from date of post-surgery baseline scan

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.

Trial Locations

Locations (1)

Glickman Urological and Kidney Institute, Cleveland Clinic, Case Comprehensive Cancer Center

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Cleveland, Ohio, United States

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