Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Urinary Bladder Neoplasms

Carcinoma, Transitional Cell

Urologic Neoplasms

Urologic Diseases

Urinary Bladder Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Transitional Cell Carcinoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Immune Checkpoint Inhibitors

Vaccines

Cisplatin

Immunomodulating Agents

Immunoglobulins

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

All patients will receive study interventions (sasanlimab and SBRT) and standard-of-care radical cystectomy.

Sasanlimab (PF-06801591) is a recombinant humanized monoclonal antibody (immunoglobulin gamma-4 with kappa light chains, IgG4 kappa) directed against programmed death 1 (PD-1). Manufactured by Pfizer, Inc.

Sasanlimab

This current study is designed to deliver a biologically equivalent dose of 43.2Gy using a strategy of HD hypo-fractionated radiation therapy 8Gy x 3 in combination with Sasanlimab

Stereotactic Body Radiation Therapy

This will include a cysto-prostatectomy in males or a radical cystectomy with anterior exenteration in females, bilateral pelvic lymph node dissection, and creation of a urinary diversion (ileal conduit, Indiana pouch or orthotopic neo-bladder). Robotic assisted or open surgery will be permitted.

Because there is currently equipoise regarding standard or extended template pelvic lymph node dissection, the limits of node dissection will not be protocol mandated. In the standard template, nodal packets will include the common iliac, external iliac, internal iliac (or hypogastric) and obturator nodes. Patients receiving an extended template will have the standard nodes with the addition of the para-aortic, para-caval, pre-sacral, and pre-sciatic node packets. The decision for urinary diversion is multifactorial involving patient factors (e.g., adequate renal function) and preference; thus, it will be made on a case-by-case basis.

Radical Cystectomy + pelvic lymph node dissection + urinary diversion

Maryam Anis

Taliah Muhammad

Maryam Anis, BS

Taliah Muhammad, BS

Raj Satkunasivam, MD, MS

Raj Satkunasivam, MD

This is a prospective, single-institution, single-arm, phase II clinical trial that tests a novel strategy of neoadjuvant Sasanlimab, an immune checkpoint inhibitor (ICI), in combination with stereotactic body radiation therapy as an in-situ vaccination in patients, who are ineligible to receive cisplatin-based chemotherapy and undergoing radical cystectomy for muscle-invasive bladder cancer.

Patients with cT2-T4a, N0, M0 urothelial bladder carcinoma (UBC) after transurethral resection of the bladder will receive 2 doses of sasanlimab (PF-06801591) at the dose of 300mg subcutaneously, followed by 3 doses of radiation (8Gy x 3) prior to surgery (radical cystectomy). Cystectomy will be planned to be done within 6 weeks of the last dose of sasanlimab.

Pathologic complete response (pT0) is the primary endpoint, in addition to a safety lead-in endpoint consisting of a composite outcome of feasibility and safety.

Exploratory biomarker analysis on tissue/blood samples will include genomic and immune-system profiling in tumor and blood before and after sasanlimab/radiation therapy, and after radical cystectomy.

Neoadjuvant Sasanlimab With Radiation as an in Situ Vaccine for Cisplatin-ineligible Muscle Invasive Bladder Cancer

A Phase II Clinical Trial of Neoadjuvant Sasanlimab and Stereotactic Body Radiation Therapy as an in Situ Vaccine for Cisplatin-ineligible Muscle Invasive Bladder Cancer

Combination of Sasanlimab and SBRT will be deemed both feasible and safe (composite outcome) if, after the treatment of 10 patients, ≥ 7 of 10 patients meet all of the following feasibility criteria:

1. Receive at least 1 dose of 2 of Sasanlimab
2. Receive at least 2 of 3 fractions SBRT
3. Undergo radical cystectomy RC within 4 weeks of completing therapy (after end of cycle 2)

and meet all of the safety criteria, defined as not experiencing any following Common Terminology Criteria for Adverse Events (CTCAE) toxicities up to 4 weeks after the completion of radical cystectomy:

1. Hematologic toxicity ≥ Grade 4
2. Non-hematologic toxicity ≥ Grade 3
3. Non-hematologic toxicity ≥ Grade 2 lasting \>1 week (except alopecia, emesis, and laboratory abnormalities)

Proportion of patients experiencing pathologic complete response (pT0) after the study treatment followed by radical cystectomy.

Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Clavien-Dindo scale is widely utilized for grading adverse events (i.e. complications) that may occur as a result of surgical procedures.

The severity of the complication increases from grade 1 to grade 5.

Patient's health related quality of life survey on 30 items including urinary symptoms, sexual function, urostomy issues, catheter use, and body image will be assessed by The European Organization for Research and Treatment of Cancer (EORTC) QOL C30-BLM 30, in order to assess changes in patient-reported quality of life at baseline and changes.

Each item is scored on a 4 point scale, with a higher score reflecting a better quality of life.

Overall Survival is defined as the duration of time from the date of treatment initiation that a patient is still alive.

RFS is defined as the time from surgery and study treatment to recurrence or death, whichever occurred first.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Neoadjuvant Sasanlimab With Radiation as an in Situ Vaccine for Cisplatin-ineligible Muscle Invasive Bladder Cancer	NCT05241340	Urothelial Carc...	Sasanlimab Stereotactic Bo... Radical Cystect...	18 Years -	The Methodist Hospital Research Institute
Neoadjuvant Sasanlimab With Radiation as an in Situ Vaccine for Cisplatin-ineligible Muscle Invasive Bladder Cancer	NCT05241340	Urothelial Carc...	Sasanlimab Stereotactic Bo... Radical Cystect...	18 Years -	The Methodist Hospital Research Institute

Spots Global Cancer Trial Database for radical cystectomy + pelvic lymph node dissection + urinary diversion