Bladder Cancer Trials

This is a phase 3, open label, single arm study of TOOKAD (padeliporfin, a type of targeted therapy) in the treatment of Upper Tract Urothelial Carcinoma (UTUC). The ENLIGHTED study will recruit patients with low-grade upper tract urothelial carcinoma in either the kidney or the ureter. The patients will be treated with TOOKAD VTP in two phases: an Induction Treatment Phase and a Maintenance Treatment Phase and will be followed up for additional 12 months in the long term (non-intervention) follow up phase. The study has 1 treatment arm: Patients entered in the study will undergo an induction treatment phase consisting of 1-3 TOOKAD VTP treatments provided 4 weeks (28 +/-3 days) apart. Patients achieving a complete response (CR, no further evidence of your cancer) after the induction treatment phase will be allowed into the maintenance treatment phase. Repeated maintenance VTP treatments during this period will be provided for patients who show evidence of tumor recurrence that is deemed treatable. During treatment, an optical light fiber will be placed at a determined target area, through a ureteroscope. Intravenous (IV) administration of TOOKAD at the dose of 3.66 mg/kg will be infused over 10 minutes. Each target area will be illuminated for 10 minutes.

This phase II trial studies how well olaparib (a type of targeted therapy/PARP inhibitor) works in treating patients with urothelial cancer (with DNA-repair defects) that has spread to other places in the body (metastatic) and usually cannot be cured or controlled with treatment. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The study has 1 arm: Treatment (olaparib) Patients receive olaparib by mouth (orally) twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity/side effects.

This is a Phase 3, open-label, randomized trial designed to evaluate the recurrence free survival of TURBT followed by cretostimogene Grenadenorepvec (a type of targeted immunotherapy) versus TURBT followed by observation for the treatment of participants with IR-NMIBC. Participants who recur after TURBT and observation will be offered treatment with cretostimogene. This study has 2 arms: Arm A: Cretostimogene after TURBT Following screening confirmation of IR-NMIBC and complete resection of the tumor, participants will be treated with adjuvant cretostimogene. Dosing and schedule will be provided by the treatment team. Arm B: Observation after TURBT Following screening confirmation of IR-NMIBC and complete resection of tumor, participants will enter observation. Participants who recur after TURBT and observation will be offered treatment with cretostimogene.

Small cell carcinoma of the bladder (SCCB) and other high-grade neuroendocrine tumors (HGNET) of the urinary tract are rare but aggressive cancers. Average survival for people diagnosed with SCCB or HGNET is about 1 year. Lurbinectedin (Zepzelca, a type of chemotherapy) and avelumab (Bavencio, a type of immunotherapy) are drugs that are approved to treat other cancers. Researchers want to see if these drugs can help people with SCCB or HGNET. The objective of this study is to assess the objective response rate (ORR, how many patients have their cancer shrink in response to taking the study medication) of lurbinectedin, either alone or in combination with avelumab, in participants with small cell carcinoma of the bladder (SCCB) or other high grade neuroendocrine tumors (HGNETs) of the urinary tract. This study has 2 treatment arms: Arm A: Lurbinectedin Lurbinectedin is administered intravenously (IV) over 1 hour on day 1 of each 21-day cycle. Arm B: Lurbinectedin + Avelumab Lurbinectedin is administered intravenously (IV) over 1 hour on day 1 of each 21-day cycle PLUS Avelumab is administered IV at 800 mg over 1 hour on day 1 of each 21-day cycle.

This is a single-arm phase 2 window of opportunity study to assess the antineoplastic activity of pemigatinib (an orally administered inhibitor of fibroblast growth factor receptors 1, 2, and 3; a type of targeted therapy) in non-muscle invasive bladder cancer (NMIBC) patients with recurrent tumors and a prior history of low- or intermediate-risk NMIBC tumors. Enrolled patients will receive pemigatinib for 4-6 weeks prior to standard of care transurethral resection of bladder tumor (TURBT). The study will assess both safety and effectiveness of pemigatinib. This study has 1 arm: Treatment: Pemigatinib Participants will take Pemigatinib is taken orally once daily on days 1 through 28 of each cycle. Patients will receive pemigatinib for 4 to 6 weeks prior to standard of care transurethral resection of bladder tumor (TURBT).

Tumors in the genitourinary tracts can occur in the kidney, bladder, prostate, and testicles and can have common and rare histologies. Some cancers that occur along the genitourinary (GU) tract are rare. Some GU tumors are so rare that they are not included in treatment studies or tissue banks. This makes it hard for researchers to determine standards of care. Researchers want to learn more about common and rare GU tumors. The objective of this study is to learn more about urinary tract cancers. Rare histological variants of the GU tract include bladder/urachal adenocarcinoma, squamous cell carcinoma, and small cell carcinoma; variants of urothelial carcinoma including plasmacytoid, sarcomatoid; renal tumors including sarcomatoid renal cell carcinoma and renal medullary carcinoma; penile cancers; micropapillary, giant cell, lipid rich, clear cell and nested variants, large cell neuroendocrine carcinoma, lymphoepithelioma-like carcinoma and mixed patterns; small cell neuroendocrine carcinoma of the prostate, testicular Sertoli or Leydig cell tumors, and papillary and chromophobe RCC. Some GU tumors occur so infrequently that they are not systematically captured by currently available registries, treatment protocols or tissue banks. The rarity of these tumors limits the sufficient numbers of patients needed in larger randomized clinical studies to characterize standard treatments or disease course. Systematic and longitudinal collection and annotation of clinical history, tissue samples, imaging studies, participant reported outcomes, and other pertinent information in participants with these rare tumors will yield future knowledge and help with the development of subsequent prospective studies to optimize diagnosis and treatment paradigms for less common GU tumors. There is no treatment given as part of this study. This will be a long-term study to comprehensively study participants with rare GU tumors. Medical history will be collected, and participants followed throughout the course of their illnesses, with particular attention to patterns of disease presentation, recurrence and progression, response to therapies, duration of responses and participant reported outcomes. Tissue samples and blood will be obtained from participants during this study. A broad spectrum of scientific experiments, including genomics and immune monitoring will be performed.

Bladder cancer is the most common urinary tract cancer and the 5th most common cancer in the US (1). Yet bladder cancer research is underfunded relative to other common cancers. As a result, bladder cancer care is prone to evidence gaps that produce decision uncertainty for both patients and clinicians. The Comparison of Intravesical Therapy and Surgery as Treatment Options (CISTO) for Bladder Cancer Study has the potential to fill these critical evidence gaps, change care pathways for the management of NMIBC (non-muscle-invasive bladder cancer), and provide for personalized, patient-centered care. The purpose of CISTO is to conduct a large prospective study that directly compares the impact of medical management versus bladder removal in recurrent high-grade NMIBC patients with BCG (Bacillus Calmette-Guerin) failure on clinical outcomes and patient and caregiver experience using standardized patient-reported outcomes (PROs). There is no treatment given as part of this protocol. Treatment will be determined by your treating physician.

This phase II trial studies how well cabozantinib (Cabometyx, a type of targeted therapy) works in combination with nivolumab (Opdivo, a type of immunotherapy) and ipilimumab (Yervoy, a type of immunotherapy) in treating patients with rare genitourinary (GU) tumors that have spread to other places in the body. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib, nivolumab, and ipilimumab may work better in treating patients with genitourinary tumors that have no treatment options compared to giving cabozantinib, nivolumab, or ipilimumab alone. All participants will receive treatment: Treatment (cabozantinib, nivolumab, ipilimumab) Patients will take cabozantinib orally (PO) QD on days 1-21 of cycles 1-4, and on days 1-28 of subsequent cycles. Patients also receive nivolumab intravenously (IV) over 30 minutes on day 1 and ipilimumab IV over 90 minutes on day 1 of cycles 1-4. Patients then receive nivolumab IV over 30 minutes on day 1 of subsequent cycles. Treatment repeats every 21 days for cycles 1-4 and every 28 days for subsequent cycles for 2 years.

This study is designed to assess the antitumor effect and safety of pembrolizumab (Keytruda, a type of immunotherapy) in combination with chemoradiotherapy (CRT, chemotherapy + radiation therapy) versus CRT alone in participants with muscle-invasive bladder cancer (MIBC). The primary hypothesis (or thought about the study) is that pembrolizumab + chemoradiotherapy is superior to placebo + chemoradiotherapy for intact bladder progression free survival. This study has 2 arms: Arm A: Pembrolizumab + Chemotherapy + Radiotherapy Participants receive pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by your provider. Pembrolizumab at 400 mg given intravenously (IV) once every 6 weeks. Details of chemotherapy and radiotherapy regimens will be discussed with your provider. Arm B: Placebo + Chemotherapy + Radiotherapy Participants receive placebo plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator. Placebo given intravenously (IV) once every 6 weeks. Details of chemotherapy and radiotherapy regimens will be discussed with your provider.

This phase II/III trial examines whether patients who have undergone surgical removal of bladder, but require an additional treatment called immunotherapy to help prevent their bladder cancer from coming back, can be identified by a blood test. Many types of tumors tend to lose cells or release different types of cellular products including their DNA which is referred to as circulating tumor DNA (ctDNA) into the bloodstream before changes can be seen on scans. Health care providers can measure the level of ctDNA in blood or other bodily fluids to determine which patients are at higher risk for disease progression or relapse. In this study, a blood test is used to measure ctDNA and see if there is still cancer somewhere in the body after surgery and if giving a treatment will help eliminate the cancer. Immunotherapy with monoclonal antibodies, such as nivolumab (Opdivo) and relatlimab, can help the body's immune system to attack cancer, and can interfere with the ability of tumor cells to grow and spread. This trial may help doctors determine if ctDNA measurement in blood can better identify patients that need additional treatment, if treatment with nivolumab prolongs patients' life, and whether the additional immunotherapy treatment with relatlimab extends time without disease progression or prolongs life of bladder cancer patients who have undergone surgical removal of their bladder. This study has 3 arms: Arm A: Nivolumab Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of tissue during screening and collection of blood throughout the trial. Patients also undergo CT or MRI scans throughout the trial. Arm B: Nivolumab + Relatlimab Patients receive nivolumab IV over 30 minutes and relatlimab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of tissue during screening and collection of blood throughout the trial. Patients also undergo CT or MRI scans throughout the trial. Arm C: ctDNA surveillance + nivolumab Patients undergo ctDNA surveillance consisting of collection of tissue and blood during screening and collection of blood only on study and during follow up. Patients who convert to ctDNA(+) during surveillance then receive nivolumab IV over 30 minutes and relatlimab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans throughout the trial.

This study will evaluate the safety and effectiveness of intravesical (directly into the bladder) administration of EG-70 in the bladder and its effect on bladder tumors in patients with non-muscle invasive bladder cancer (NMIBC). The study will include patients with NMIBC for whom BCG therapy is unresponsive and are recommended for radical cystectomy, or high-risk NMIBC patients who are BCG-naïve or have received incomplete BCG treatment. EG-70 is a novel non-viral gene therapy. EG-70 is designed to elicit a local immune response following delivery of the study gene therapy to the bladder urothelium (cells lining the bladder). This approach of local administration through bladder instillation has the potential to induce a potent immune response exclusively at the site of the tumor, resulting in greater therapeutic benefit while reducing undesirable systemic toxicity. All subjects will receive treatment will EG-70. Dose level will be provided by the treatment site. Patients will receive up to 4 cycles of EG-70 administered as a bladder instillation of a 50 mL volume of study drug via catheter with a targeted retention time of 60 minutes. One cycle lasts approximately 12 weeks.

Genitourinary cancers are some of the most common types of cancer. They are lethal when they spread. The drug M7824 blocks the paths that cancer cells use to stop the immune system from fighting cancer. The drug M9241 triggers the immune system to fight cancer. Researchers want to learn if these drugs can help fight these cancers when given with and without Stereotactic Body Radiation Therapy (SBRT) radiation. This study has 3 treatment arms: Arm A: Treatment with M7824 and deescalating (decreasing) doses of M9241, if appropriate Drug: M7824 1200 mg administered intravenously (IV) in clinic every two weeks while on M9241 and with or without SBRT Drug: M9241 an initial dose of 16.8 mcg/kg administered subcutaneously (SC or SQ) every 4 weeks while on M7824 and with or without SBRT Arm B: Treatment with M7824 and deescalating doses of M9241 (if appropriate) with sequential SBRT Drug: M7824 1200 mg administered IV every two weeks while on M9241 and with or without SBRT Drug: M9241 an initial dose of 16.8 mcg/kg administered subcutaneously every 4 weeks while on M7824 and with or without SBRT Radiation: Stereotactic body radiation therapy (SBRT) a fixed dose of 8 Gy x 3 fractions sequential or concurrent with M7824 and M9241 Arm C: Treatment with M7824 and deescalating doses of M9241 (if appropriate) with concurrent SBRT Drug: M7824 1200 mg administered IV every two weeks while on M9241 and with or without SBRT Drug: M9241 an initial dose of 16.8 mcg/kg administered subcutaneously every 4 weeks while on M7824 and with or without SBRT Radiation: Stereotactic body radiation therapy (SBRT) a fixed dose of 8 Gy x 3 fractions sequential or concurrent with M7824 and M9241

This is a registry study to gather more information on the current use of Blue Light Cystoscopy with Cysview (BLCC) in urologists' practices. The Blue Light Cystoscopy with Cysview Registry is a web-based program supported by Global Vision Technologies. Data will be captured longitudinally over five (5) years on patients from each enrolled site. Each center will enter their respective site's patient data electronically. This study does NOT offer any treatment.

This phase III trial studies how well chemotherapy and radiation therapy work with or without atezolizumab (Tecentriq, a type of immunotherapy) in treating patients with localized muscle invasive bladder cancer. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Chemotherapy drugs, such as gemcitabine, cisplatin, fluorouracil and mitomycin-C, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with radiation therapy may kill more tumor cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving atezolizumab with radiation therapy and chemotherapy may work better in treating patients with localized muscle invasive bladder cancer compared to radiation therapy and chemotherapy without atezolizumab. This study has 2 treatment arms: Arm A: Radiation Therapy (RT) + Chemotherapy Patients undergo RT Monday-Friday for up to 7 weeks. Patients also receive chemotherapy based on physician's choice of gemcitabine intravenously (IV) twice weekly for 6 weeks, OR cisplatin IV weekly for 6 weeks concurrent with RT, OR fluorouracil IV on same days as doses 1-5 and 16-20 of radiation therapy PLUS mitomycin IV on day 1 of radiation therapy in the absence of disease progression or unacceptable toxicity. Arm B: RT + chemotherapy + atezolizumab Patients undergo RT Monday-Friday for up to 7 weeks and receive chemotherapy based on physician's choice as in Arm A. Patients also receive atezolizumab IV over 60 minutes on day 1 of chemotherapy. Treatment repeats every 21 days for a total of 6 months (9 doses total) in the absence of disease progression or unacceptable toxicity.

This is an open label Phase 1b/2 study to evaluate the effectiveness and safety of ACR-368 (Prexasertib, a type of targeted therapy) alone or in combination with low dose gemcitabine (Gemzar, a type of chemotherapy) in participants with platinum-resistant urothelial carcinoma based on Acrivon's OncoSignature test status. Participants will be selected for predicted effectiveness of ACR-368 using the OncoSignature Companion Diagnostic test. Participants will be allocated to 1 of 2 arms based on the OncoSignature result: Arm 1: OncoSignature Positive tumors Arm 2: OncoSignature Negative tumors or tumors that cannot be evaluated Participants in Arm 1 will receive ACR-368 alone. Dose and dosing schedule will be provided by the treatment team. Participants in Arm 2 will receive the combination of ACR-368 and low-dose gemcitabine. Doses and dosing schedule will be provided by the treatment team.

This study will test a drug called enfortumab vedotin (PADCEV, a type of targeted therapy) in participants with a type of bladder cancer called non-muscle invasive bladder cancer (NMIBC). This study will also evaluate what the side effects are and if the drug works to treat NMIBC. A side effect is anything a drug does to your body besides treating your disease. In this study enfortumab vedotin will be put into the bladder using a catheter (intravesicular). A catheter is a thin tube that can be put into your bladder. All participants will receive enfortumab vedotin. During the induction phase, participants will receive enfortumab vedotin once a week for 6 weeks. During the maintenance phase, participants will receive enfortumab vedotin once a month for 9 doses. Dosage will be provided by treatment team.

This is a phase III, single-arm, multicenter, international study to assess the effectiveness and safety of ONCOFID-P-B (a type of chemotherapy) following intravesical instillation (infused directly into the bladder) in adult patients with histologically and cytologically confirmed carcinoma in situ (CIS) of the bladder, with or without papillary disease, who are unresponsive to Bacillus Calmette–Guérin (BCG) therapy and unwilling or unfit to undergo radical cystectomy. All subjects will receive treatment. ONCOFID P-B (PACLITAXEL-HYALURONIC ACID) ONCOFID P-B will be infused directly into the bladder (intravesically) once a week for 12 consecutive weeks (induction phase). Patients who achieve a complete response (meaning the cancer can no longer be seen on imaging) at the end of the induction phase will enter the maintenance phase, during which ONCOFID-P-B is administered once a month for 12 months until recurrence or progression of the disease.

This is a Phase I/Phase II study. Phase 1 will be conducted in BCG-unresponsive (a type of chemotherapy given directly in the bladder) patients with non-metastatic invasive bladder cancer (NMIBC) to establish the safety of durvalumab (Imfinzi, a type of immunotherapy) given:

1. alone

2. in combination with BCG

3. in combination with external beam radiation therapy (EBRT)



Provided safety is demonstrated, the study will proceed to phase 2 testing. Phase 2 will be conducted in the BCG-relapsing (meaning the cancer returns after treatment with BCG) NMIBC population. In phase 2, BCG-relapsing NMIBC subjects will be randomized to treatment with:

1. intravesical (directly in the bladder) BCG in combination with durvalumab

2. durvalumab in combination with radiation (EBRT)

3. retreatment with intravesical BCG alone



In addition to providing additional safety data on the combination regimens studied, phase 2 will provide preliminary information on effectiveness for BCG-relapsing NMIBC subjects.

Durvalumab is given intravenously (IV) in clinic. BCG is instilled (infused) directly in to the bladder in clinic. Frequency of visit dates will vary depending on which treatment arm you are assigned to.

The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435 (a type of targeted therapy). LOXO-435 may be used to treat cancer of the cells that line the urinary system and other solid tumor cancers that have a change in a particular gene (known as the FGFR3 gene). Participation could last up to 30 months (2.5 years) and possibly longer if the disease does not get worse. This study has 2 potential treatment arms: Arm A: LOXO-435 alone LOXO-435 will be administered orally (by mouth, PO) at various dosages. Dosage will be provided by the treatment team. Arm B: LOXO-435 + Pembrolizumab (Keytruda, a type of immunotherapy) LOXO-435 administered orally in combination with pembrolizumab administered intravenously (IV). Dosage and dosing schedule will be provided by the treatment team.

This trial will evaluate the use of combination pembrolizumab (Keytruda, a type of immunotherapy) and enfortumab vedotin (PADCEV, a type of targeted therapy) for patients with high grade non-metastatic (cN0/NxMx, no measurable regional lymph nodes, no metastases) upper tract urothelial cancer (UTUC), preferring to forego standard of care radical nephroureterectomy (RNU) surgery. Currently these patients would not be suitable candidates for neoadjuvant trials, as the patients’ intention is to forego surgery. The patients are also not candidates for metastatic trials, as the patients have no measurable metastasis. The Investigators hypothesize the combination of pembrolizumab and enfortumab vedotin for patients with high grade cN0/NxMx UTUC deferring RNU will lead to event free survival outcomes similar to that achieved by RNU in a historic dataset. This study has 1 treatment arm: Pembrolizumab + Enfortumab Vedotin Enfortumab vedotin will be administered on Days 1 and 8 of every 21 day cycle, at 1.25mg/kg by intravenous (IV) infusion given over approximately 30 minutes. Pembrolizumab will be administered on Day 1 of every 21 day cycle at 200mg by IV infusion over approximately 30 minutes. Enfortumab vedotin and Pembrolizumab may be administered for up to total of 35 cycles (approximately 2 years).

The purpose of this study is to assess the safety and efficacy of avelumab (a type of targeted therapy) in combination with other anti-tumor agents as a maintenance treatment in participants with bladder cancer. This study has 4 treatment arms: Arm A: Avelumab alone Participants will receive avelumab by intravenous (IV) infusion at a dose of 800 milligrams (mg) once every 2 weeks (Q2W) until unacceptable toxicity, withdraw consent or initiation of a new treatment. Arm B: Avelumab + Sacituzumab Govitecan (Trodelvy, a type of targeted therapy) Participants will receive Avelumab and noted above PLUS sacituzumab govitecan by IV infusion at dose of 10 mg per kilogram (mg/kg) of body weight once a week (Q1W) on Day 1 and 8 of 21-day treatment cycles until unacceptable toxicity, withdraw consent or initiation of a new treatment. Arm C: Avelumab + M6223 (a type of targeted therapy) Participants will receive Avelumab and noted above PLUS M6223 by IV infusion at dose of 1600 mg Q2W until unacceptable toxicity, withdraw consent or initiation of a new treatment. Arm D: Avelumab + NKTR-255 (Nektar, a type of immunotherapy) Participants will receive Avelumab and noted above PLUS NKTR-255 by IV infusion at a dose of 3 micrograms per kilogram body weight (mcg/kg) once every 4 weeks (Q4W) until unacceptable toxicity, withdraw consent or initiation of a new treatment.

This is a Phase 3, open-label, single arm trial designed to evaluate Cretostimogene (a type of targeted immunotherapy) patients with non-muscle invasive bladder cancer (NMIBC) who have failed prior Bacillus Calmette-Guerin (BCG, a type of immunotherapy) therapy. The objective of this study is to determine the response rate for subjects who did not respond to BCG therapy. The study has 1 treatment arm: Arm A: Cretostimogene Cretostimogene will be administered by intravesical instillation (directly into the bladder) every week for 6 treatments on Weeks 1, 2, 3, 4, 5, and 6. If the patient has recurrence at Week 13 or at any timepoint after that, the patient will receive a second course of 6 weekly treatments (Weeks 13, 14, 15, 16, 17, and 18.). If the tumor has not returned, the patient will receive 3 weekly treatments every 12 weeks (approximately 3 months) starting Weeks 13, 14, and 15 through Week 51 (approximately 12 months), and then every 6 months starting at Weeks 73, 74, and 75 (approximately 18 months) through Month 36.

The purpose of this study is to evaluate mood changes in patients with Non-Muscle Invasive Bladder Cancer who are receiving intravesical Bacillus Calmete-Guerin (BCG, a type of vaccine therapy infused directly into the bladder). Patients with Non-Muscle Invasive Bladder Cancer receiving intravesical treatments are eligible to participate in this study. Participation involves providing research blood and urine samples prior to the start of treatment and throughout the treatment course. The study team will also collect participant's medical history and clinical information. Participants will be asked to complete questionnaires and daily mood diaries. There is no treatment provided as part of this study.

The purpose of this clinical trial is to determine if prostate-capsule-sparing cystectomy (surgery to remove the bladder) improves functional outcomes without comprising cancer outcomes in male patients receiving a radical cystectomy. Patients will be randomized to one of two groups: prostate capsule-sparing radical cystectomy or nerve-sparing radical cystectomy. Patients will be monitored following standard of care guidelines and clinical data will be collected. Patients in both groups will be asked to complete an erectile function questionnaire at multiple timepoints. Patients who receive an orthotopic neobladder (a pouch created from a portion of the small bowel that functions as a bladder) will be asked to complete a questionnaire to monitor urinary function at multiple timepoints. Patient adverse events will be monitored to ensure patients safety. This study has 2 arms: Arm A: Prostate Capsule-Sparing Radical Cystectomy Patients randomized to this arm will receive the prostate capsule-sparing surgery performed in the form of standard simple prostatectomy. Patients will also have a cystectomy with one of the following urinary diversions: ileal conduit, Indiana Pouch, or orthotopic neobladder. Arm B: Nerve-Sparing Radical Cystectomy Patients randomized to this arm will receive the nerve-sparing surgery will be performed in the form of the standard nerve-sparing radical prostatectomy. Patients will also have a cystectomy with one of the following urinary diversions: ileal conduit, Indiana Pouch, or orthotopic neobladder.

A Global Study to Determine the Effectiveness and Safety of Durvalumab (a type of immunotherapy) in combination with Tremelimumab (a type of immunotherapy) and Enfortumab Vedotin (a type of targeted therapy) or Durvalumab in Combination With Enfortumab Vedotin for Perioperative (around the time of surgery) Treatment in Patients Ineligible for Cisplatin Undergoing Radical Cystectomy for Muscle Invasive Bladder Cancer This study has 3 treatment arms: Arm A: Durvalumab + Tremelimumab + Enfortumab vedotin Participants will receive 3 preoperative 21-day cycles of Durvalumab + Tremelimumab + Enfortumab Vedotin, followed by radical cystectomy, followed by 1 cycle of postoperative Tremelimumab and 9 cycles of Durvalumab. Each postoperative cycle is 28 days. Durvalumab 1500 mg by intravenous (IV) infusion given on Day 1 of each cycle. Tremelimumab 75 mg by intravenous (IV) infusion given on Cycle 1 Day 1 and Cycle 2 Day 8 preoperatively and on Cycle 1 Day 1 postoperatively. Enfortumab Vedotin 1.25 mg/kg by intravenous (IV) infusion given on Days 1 and 8 of each 21-day cycle Arm B: Durvalumab + Enfortumab vedotin Participants will receive 3 preoperative 21-day cycles of Durvalumab + Enfortumab Vedotin, followed by radical cystectomy, followed by 9 cycles of Durvalumab. Each postoperative cycle is 28 days. Durvalumab 1500 mg by intravenous (IV) infusion given on Day 1 of each cycle. Enfortumab Vedotin 1.25 mg/kg by intravenous (IV) infusion given on Days 1 and 8 of each 21-day cycle Arm C: Straight to cystectomy Radical cystectomy alone. Participants receive standard of care surgery alone.

This is a single arm, Phase II trial involving the use of atezolizumab (Tecentriq, a type of immunotherapy) plus platinum (a type of chemotherapy) and etoposide (a type of chemotherapy) for patients with locally advanced urothelial cancer. The primary goal of this trial is to assess the pathologic complete response rate (meaning there is no longer any cancer visible on imaging scans) at time of cystectomy (the surgical removal of the bladder) in patients after being treated with a combination therapy of atezolizumab, platinum, and etoposide. The study population will include male and female patients over the age of 18 with invasive small cell / neuroendocrine carcinoma of the bladder, with or without urothelial cancer component, who are eligible for platinum based chemotherapy and immunotherapy. All patients will be fit to undergo surgical resection of their cancer by cystectomy. This study has 1 treatment arm: Atezolizumab with Platinum and Etoposide, followed by cystectomy. Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 mg on Day 1 of every 21 day cycle (1 cycle = 21 days), with chemotherapy, for 4 cycles. Following cystectomy, Atezolizumab maintenance will continue once every 21 days for up to 1 year. Chemotherapy will include Etoposide given IV on Days 1 - 3 every cycle for the first 4 cycles. Chemotherapy will include either Carboplatin given IV on Day 1 every cycle for the first 4 cycles OR Cisplatin given IV on Day 1 every cycle for first 4 cycles. Cystectomy should be performed within 42 days after completion of last administered study therapy of induction phase (first 4 cycles of chemotherapy). Cystectomy should be performed within 42 days after completion of last administered study therapy (after the first 4 cycles of Atezolizumab + chemotherapy).

The study hypothesis is that patients with non-muscle invasive bladder cancer (NMIBC) who have not received treatment with BCG (a type of immunotherapy infused directly into the bladder) will have equal or better outcomes when treated with intravesical (infused directly into the bladder) Gemcitabine + Docetaxel (GEMDOCE, a type of chemotherapy). The purpose of this study is to test whether Gemcitabine + Docetaxel is a better or worse treatment than the standard of care BCG therapy. This study has 2 arms: Arm A: Gemcitabine + Docetaxel Intravesical infusion once a week for 6 consecutive weeks followed by monthly infusions during maintenance for 2 years. Arm B: BCG (Bacillus Calmette Guerin) Intravesical infusion once a week for 6 consecutive weeks during induction followed by weekly infusions for 3 consecutive weeks at months 3, 6, 12, 18, 24, 30, and 36 months.

This study is being done to see if a drug called disitamab vedotin (a type of targeted therapy), alone or with pembrolizumab (Keytruda, a type of immunotherapy), works to treat HER2 expressing urothelial cancer. It will also test how safe the drug is for participants. Participants will have cancer that has spread in the body near where it started (locally advanced) and cannot be removed (unresectable) or has spread through the body (metastatic). It will also study what side effects happen when participants get the drug. A side effect is anything a drug does to your body besides treating the disease. All patients will receive treatment with either: Disitamab vedotin alone: Given into the vein (IV; intravenous) every 2 weeks OR Disitamab vedotin + pembrolizumab: Disitamab vedotin is given into the vein (IV; intravenous) every 2 weeks + Pembrolizumab given by IV on Day 1 of each 6-week cycle.

This phase III trial compares the effect of adding durvalumab (Imfinzi, a type of immunotherapy) to chemotherapy versus chemotherapy alone before surgery in treating patients with upper urinary tract cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as methotrexate, vinblastine, doxorubicin, cisplatin, and gemcitabine work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Durvalumab in combination with chemotherapy before surgery may enhance the shrinking of the tumor compared to chemotherapy alone. This study has 3 treatment arms: Arm A: Durvalumab + chemotherapy Patients receive durvalumab intravenously (IV) over 60 minutes on day 1 of chemotherapy cycles 1 and 3. Patients also receive methotrexate IV over 2-3 minutes, vinblastine sulfate IV, doxorubicin IV, cisplatin IV over at least 2 hours on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery. Arm B: Chemotherapy Patients also receive methotrexate IV over 2-3 minutes, vinblastine sulfate IV, doxorubicin IV, cisplatin IV over at least 2 hours on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery. Arm C: Durvalumab + Gemcitabine Patients receive durvalumab IV over 60 minutes on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery.

This is an open-label phase II study assessing the activity of cabozantinib (Cabometyx, a type of targeted therapy) combined with atezolizumab (Tecentriq, a type of immunotherapy) in patients with resectable muscle-invasive urothelial carcinoma who are ineligible for cisplatin-based therapy or decline cisplatin-based therapy (chemotherapy). The study has one treatment arm: Cabozantinib 40 mg orally (by mouth or PO) once daily for 9 weeks PLUS Atezolizumab 1200 mg given intravenously (IV) once every 3 weeks for 3 doses.

This phase II trial compares the effect of adding radiation therapy to an immunotherapy drug called atezolizumab (Tecentriq) vs. atezolizumab alone in treating patients with urothelial cancer that has spread to other places in the body (metastatic). The addition of radiation to immunotherapy may shrink the cancer, but it could also cause side effects. Immunotherapy with monoclonal antibodies such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy (SBRT) is a type of radiation therapy that uses high energy x-rays to kill tumor cells and shrink tumors. This method uses special equipment to position a patient and precisely deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and may cause less damage to normal tissue than conventional radiation therapy. The combination of atezolizumab and radiation therapy may be more efficient in killing tumor cells. This study has 2 treatment arms: Arm A: Atezolizumab alone Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Arm B: Atezolizumab + SBRT Patients receive atezolizumab as in Arm A. Patients also undergo SBRT for 3 fractions over 2 weeks in the absence of disease progression or unacceptable toxicity.