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Brief Title: Robotic Vascularized Composite Bladder Allograft Transplantation Surgery for the Treatment of Patients With Bladder Cancer

Robotic Vascularized Composite Bladder Allograft Transplantation: A Phase 0 (First-in-Human), Single Institutional Study for Deceased Donor Bladder Transplantation

INTRODUCTION

  • Org Study ID: 4B-21-5
  • Secondary ID: NCI-2022-00076, 4B-21-5, P30CA014089
  • NTC ID: NCT05462561
  • Sponsor: University of Southern California

BRIEF SUMMARY

This early phase I trial tests the feasibility, functionality, and sustainability of robotic vascularized composite bladder allograft transplantation in treating patients with bladder cancer. A vascularized bladder allograft transplantation may provide a more durable and better tolerated alternative to urinary diversion using bowel in patients with bladder cancer.

DETAILED DESCRIPTION

PRIMARY OBJECTIVE:

I. To perform phase 0 studies demonstrating the feasibility of robotic vascularized composite bladder allograft (VCBA) transplantation from a brain-dead deceased donor.

SECONDARY OBJECTIVES:

I. To describe the adverse events associated with VCBA transplantation. II. To describe a feasible immunosuppression regimen for patients undergoing VCBA transplantation.

III. To evaluate allografted bladder functionality (storage and emptying) after transplantation.

OUTLINE:

Patients undergo robotic vascularized composite bladder allograft (VCBA) transplantation.

After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months and then every 3 months for the first year and once a year thereafter.

  • Overall Status
    Recruiting
  • Start Date
    October 3, 2022
  • Phase
    Not Applicable
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Technical success of vascularized composite bladder allograft (VCBA) transplantation

Primary Outcome 1 - Timeframe: At completion of transplantation procedure

CONDITION

  • Muscle Invasive Bladder Carcinoma
  • Stage II Bladder Cancer AJCC v8
  • Stage IIIA Bladder Cancer AJCC v8

ELIGIBILITY

Inclusion Criteria:
Age 18-65 years.
Positive history of one of the following:
Bladder pathology resulting in poor compliance and resultant upper tract (kidney and ureteral) pathology, demonstrated by hydronephrosis with resultant kidney disease.

- Localized, non-metastatic, muscle-invasive (cT2 or T3) bladder cancer requiring radical cystectomy. Though challenging to predict, less than 30% of accrued patients are expected to have bladder cancer as the etiology of their cystectomy.

- Patients that are on immunosuppression for pre-existing solid organ transplantation will be included in this study.

- Patient agrees to comply with the protocol and states a dedication to the immunomodulatory treatment regime.

- Patients must demonstrate appropriate manual dexterity or sufficient assistance at home to perform clean intermittent catheterizations as needed. The patient (or assistant) must demonstrate proficiency in performing clean intermittent catheterization during pre-transplant workup.

- No co-existing medical condition which, in the opinion of the study team, could affect the immunomodulatory protocol, surgical procedure, or functional results (see Exclusion Criteria below). If the condition is amenable to treatment, the study team must agree that said condition should not significantly enhance the surgical risks of genitourinary transplantation. Examples of such medical conditions would include burden of atherosclerotic disease that would preclude vascular anastomosis, and psychiatric disorders that would preclude reliable adherence to medications.

- No active co-existing psychosocial problems (i.e., alcoholism, drug abuse).

- Negative crossmatch with donor.

- DONOR: Any potential brain dead donor considered for solid organ transplant.

- DONOR: Age 18-65 years.

- DONOR: Stable, meaning no requirement of excessive vasopressors for maintaining blood pressure.

- DONOR: ABO compatibility.

- DONOR: Negative cross-match with recipient.
Exclusion Criteria:
Positive history of one of the following medical co-morbidities:
Human immunodeficiency virus [HIV] (active or seropositive), active hepatitis B or C, viral encephalitis, untreated sepsis, active tuberculosis, viral encephalitis, toxoplasmosis, varicella zoster virus.

- Conditions that may impact the success of the surgical procedure or increase the risk of postoperative complications including inherited coagulopathies like hemophilia, Von-Willebrand's disease, protein C and S deficiency, thrombocythemia, thallassemia, sickle cell disease.
Mixed connective tissue diseases and collagen disorders (can result in poor wound healing after surgery), including:
Mixed connective tissue disorder

- Severe deforming rheumatoid arthritis

- Infectious, post-infectious, or inflammatory (axonal or demyelinating) neuropathy

- Ehler-Danlos syndrome

- Lipopolysaccharidosis or amyloidosis (effects nerve regeneration).

- Impaired liver function as evaluate by liver function panel, including the presence of hyperbilirubinemia, elevated aspartate aminotransferase/ alanine aminotransferase (AST/ALT), and the presence of secondary coagulopathy, measured by prothrombin, international normalized ratio, and partial thromboplastin time.

- Severe anemia (hemoglobin < 7 g/dL), leukopenia (WBC < 3 x 10 ^ 9 cell/L), or thrombocytopenia (platelets < 20 x10 ^ 9 cells/L).
Oncology patient specific:
History of non-urothelial malignancy in past 5 years, with the exception of non-melanomatous skin cancer

- History of malignancy involving metastases.

- Sensitized recipients; panel reactive antibody (PRA) < 80%, with negative crossmatch to donor and no evidence of donor-specific antibody at time of transplant. - Patients unable to receive adequate follow-up care and/or unable to receive immunosuppression due to geographic, financial or other reasons. - Patients with a smoking history who cannot demonstrate smoking cessation for a period of 6 months prior to listing and a desire to abstain from post-operative smoking will be excluded. - Records of poor medical compliance, documented psychological disorder(s), substance abuse or incomplete psychological clearance. - Particular attention will be paid to the candidate's compliance and their desire to undergo the offered procedure. While there is no "score" on any particular evaluation that would rule out a patient, certain factors can aid in the identification of patients who for example may not have the ability to comply with the medical directives necessary to care for a genitourinary transplant, or psychologically are not prepared for transplant, or who have unrealistic expectations about the transplant. The decision on eligibility is a team decision. All members of the team will discuss each candidate in a multidisciplinary meeting and reasons for concern over eligibility will be discussed at a Selection Committee Meeting (per University of Southern California Transplant Center Policy). In circumstances where the candidate is considered to be less suitable, they could be given an opportunity to address these issues either through individual counseling or further education and then be reconsidered as a potential candidate. Every effort to prevent a request for allograft removal will be made. Towards these ends, a two-part initial psychiatric consultation will be rendered in addition to psychosocial evaluations already accounted for in the social work and transplantation evaluation prior to listing. The first visit focuses on background history and standard contraindications to transplantation, while the second visit is a more thorough discussion of the challenges ahead for the potential recipient and how these challenges relate to their strengths and vulnerabilities. If at this phase, or any subsequent one, significant psychological need emerges, the patient will be referred to another mental health professional for ongoing treatment with frequent communication between that provider and the transplant psychiatrist. The same psychiatrist responsible for listing and taking part in the protocol will not provide this treatment, given the potentially conflicting obligations involved and the disincentive present for the patient to be completely honest. If a greater than 6 month period of time elapses between listing and transplantation, a follow-up visit with psychiatry and social work will be arranged. - DONOR: Unresolved sepsis. - DONOR: Known history of urothelial or prostate cancer/malignancy. - DONOR: Known history of bladder or prostate surgery. - DONOR: Abnormal bladder capacity. - DONOR: Active sexually transmitted disease. - DONOR: Active cytomegalovirus (CMV), Epstein-Barr virus (EBV), or tuberculosis (TB) infections. - DONOR: Hepatitis B virus (HBV) core antibody, surface antigen, or DANN positive. - DONOR: Hepatitis C virus (HCV) antibody or viral load+. - DONOR: Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS).

Gender: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Inderbir Gill

Role: Principal Investigator

Affiliation: University of Southern California

Overall Contact

Name: Inderbir Gill

Phone: N/A

Email: N/A

LOCATION

Facility Status Contact
Facility: USC / Norris Comprehensive Cancer Center
Los Angeles, California 90033
United States
Status: Recruiting Contact: Contact
Ileana Aldana
323-865-3000
Ileana.aldana@med.usc.edu