Bladder Cancer Trials

This phase II trial studies how well atezolizumab (a type of immunotherapy) works in treating patients with non-muscle invasive bladder cancer that has come back and has not responded to treatment with Bacillus Calmette-Guerin (BCG). Monoclonal antibodies, such as atezolizumab, may block specific proteins found on white blood cells which may strengthen the immune system and control tumor growth. The study has 1 arm: Atezolizumab Patients receive atezolizumab intravenously (IV) over 60 minutes on day 1 of each 21 day cycle. Treatment repeats every 21 days for up to 17 courses (51 weeks) in the absence of disease progression or unacceptable toxicity.

This is a clinical trial studying the administration of NanoDoce (docetaxel, a type of chemotherapy) as a direct injection to the bladder wall immediately after tumor resection and as an intravesical instillation (put directly in to the bladder using a catheter). All participants will receive NanoDoce, and will be evaluated for safety and tolerability, as well as the potential effects of NanoDoce on urothelial carcinoma. There are 2 treatment cohorts: Cohort 1: Non-Muscle Invasive Bladder Cancer Subjects will receive NanoDoce injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT). Visit 2 instillation, all subjects will receive an initial intravesical instillation within 2 hours of direct injection. Induction and Maintenance Instillations, all subjects will receive intravesical instillations in an Induction Period (6 weekly NanoDoce intravesical instillations, followed by 6 weeks of rest) and a Maintenance Period (3 weekly NanoDoce intravesical instillations, followed by 9 weeks of rest). Cohort 2: Muscle Invasive Bladder Cancer Subjects will receive NanoDoce injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT). Visit 2 instillation, all subjects will receive an initial intravesical instillation within 2 hours of direct injection. Subjects will then receive standard of care therapy.

This study aims to determine the best dose of cabozantinib plus nivolumab when given with and without ipilimumab. Nivolumab and ipilimumab are drugs from a class of immunotherapy agents called monoclonal antibodies that have recently been approved as treatment for several other cancers. While they each have different target proteins, both drugs prevent the expression of a specific protein either on or produced by tumor cells that stops the immune system from attacking the cancer. These drugs free the T-cells (a type of immune cell) so that they can trigger an immune response that kills tumor cells and halts the growth of the cancer. Cabozantinib is a targeted therapy currently approved for the treatment of other cancers because of its ability to stop tumor growth and prevent the formation of new blood vessels supplying tumors. Part one of the study involves a 28-day cycle during which nivolumab is administered on days 1 and 15 and cabozantinib is taken as an oral medication daily. Part two of the study consists of 21-day cycles. During the first four cycles, cabozantinib is taken as an oral medication daily and both nivolumab and ipilimumab are administered through an IV on day 1. After these first four cycles, part two begins the same dosing regimen as part one.

The purpose of this study is to determine if TAR-200, an investigational drug-delivery system, is safe and tolerable in patients with muscle-invasive bladder cancer (MIBC) who are unfit for radical cystectomy (complete surgical removal of the bladder). This study only has one arm, for patients who are radical cystectomy ineligible: TAR-200 is placed into the bladder through an Inserter and gradually releases gemcitabine (a type of chemotherapy) during the 21-day indwelling period before being removed. Subjects will undergo an 84-day induction period comprised of four consecutive 21-day dosing cycles. Subjects may undergo up to 3 additional dosing cycles as maintenance.

A study to evaluate Nivolumab (Opdivo) or Nivolumab Plus Experimental Medication BMS-986205 with or without BCG (Bacillus Calmette–Guérin, a type of chemotherapy instilled directly in to the bladder) in BCG-Unresponsive non-muscle invasive Bladder Cancer. This study has 4 arms: dosing of each drug and combination will be given at time of enrollment. Arm A: Nivolumab monotherapy Arm B: Nivolumab + BCG Arm C: Nivolumab + BMS-986205 Arm D: Nivolumab + BMS-986205 + BCG

This is a randomized phase 2 trial of gemcitabine (a type of chemotherapy) + carboplatin (a type of chemotherapy) + nivolumab (a type of immunotherapy) or gemcitabine + oxaliplatin (a type of chemotherapy) + nivolumab for the treatment of cisplatin-ineligible patients with metastatic urothelial cancer. Randomization will be stratified on the metastasis status (lymph node only vs. other metastatic sites). This study has 2 arms: dosing schedule will be given at time of enrollment. Both treatment arms will receive up to 6 cycles of combination therapy. Patients with at least stable disease at the completion of 6 cycles of treatment may continue "maintenance" single agent nivolumab for up to 24 cycles. Patients who require discontinuation of chemotherapy (i.e., gemcitabine plus carboplatin or gemcitabine plus oxaliplatin) prior to Cycle 6, but who have at least stable disease, may be considered for ongoing treatment with single-agent nivolumab on the "maintenance" phase after discussion with the sponsor-investigator. Arm A: Gemcitabine plus carboplatin plus nivolumab Gemcitabine is given intravenously (IV) at 1000 mg/m2. Carboplatin is given IV at AUC 4.5 (based on the Calvert formula). Nivolumab is given IV at 240 mg. Arm B: Gemcitabine plus oxaliplatin plus nivolumab Gemcitabine and nivolumab will be given the same as in Arm A. Oxaliplatin is given IV at 130 mg/m2.

This randomized phase III trial studies how well pembrolizumab (a type of immunotherapy) works in treating patients with bladder cancer that has spread from where it started to nearby tissue or lymph nodes (metastatic). Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

Patients will be randomized to one of two arms:

Arm A Observation

Patients undergo observation only (no treatment).

Arm B Pembrolizumab

Patients receive pembrolizumab by intravenous (IV, in clinic) infusion over 30 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

This study aims to determine whether adding avelumab to best-supportive care has any effect on overall survival. Avelumab is a developing immunotherapy agent called a PD-1 inhibitor. Cancer cells bind to a specific molecule, which allows the cancer to grow without being attacked by the immune system. Avelumab interferes with the formation of this bond, which then enables the immune system to recognize and kill the cancer cells. Persons eligible for this study are those with locally advanced or metastatic urothelial cancer who had stage IV cancer previously treated with 4-6 rounds of chemotherapy. Participants will be randomly separated into two groups. Both groups will receive the standard best supportive care, which can include pain and symptom management, among other things. One group will additionally receive IV avelumab every two weeks in four-week cycles.

This is a randomized, open-label, controlled, multi-center, global Phase III study to determine the effectiveness and safety of combining durvalumab (a type of immunotherapy) ± tremelimumab (a type of immunotherapy) with standard of care (SoC) chemotherapy (cisplatin + gemcitabine or carboplatin + gemcitabine doublet) followed by durvalumab monotherapy versus SoC alone as first-line chemotherapy in patients with unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra). This study has 3 treatment arms; all treatments are given in clinic. Standard of care (SoC) chemotherapy regimens are given following local clinic and provider orders. Arm A: Durvalumab in Combination with SoC Chemotherapy Durvalumab given intravenously (IV) every 3 weeks with SoC chemotherapy, followed by durvalumab monotherapy every 4 weeks. All patients will receive one of the following standard of care (SoC) chemotherapy regimens every 3 weeks for 6 cycles: • cisplatin+ gemcitabine • If the patient is cisplatin-ineligible, carboplatin + gemcitabine Arm B: Durvalumab in Combination with Tremelimumab + SoC Chemotherapy Durvalumab and Tremelimumab given intravenously (IV) every 3 weeks with SoC chemotherapy, followed by durvalumab given alone every 4 weeks Tremelimumab will be provided for 4 cycles. All patients will receive one of the following standard of care (SoC) chemotherapy regimens every 3 weeks for 6 cycles: • cisplatin+ gemcitabine • If the patient is cisplatin-ineligible, carboplatin + gemcitabine Arm C: SoC Chemotherapy Patients will receive one of the following standard of care (SoC) chemotherapy regimens every 3 weeks for 6 cycles: • cisplatin+ gemcitabine • If the patient is cisplatin-ineligible, carboplatin + gemcitabine

The study is investigating the effectiveness and safety of UroGen's UGN-102 to treat patients with Low Grade (LG) Non Muscle Invasive Bladder Cancer (NMIBC) at intermediate risk of recurrence. UGN-102 is a reverse thermal hydrogel formulated with Mitomycin (MMC). The product is specifically formulated to achieve a liquid state at 4°C and to transition to a water-soluble gel at body temperature. The advantage of delivering Mitomycin to the urinary bladder using UGN-102 relies on preclinical and clinical literature documenting that concentration and dwell time correlate directly with the therapeutic efficacy (effectiveness) of MMC when used to treat Urothelial Carcinoma (UC). Treatment: UGN-102 Six intravesical instillations (placed directly in to the bladder using a urinary catheter) of UGN-102 will be given weekly. Patients who achieve a complete response (CR, no signs of any remaining cancer) to treatment will receive monthly intravesical instillation of UGN-102 and will continue to be monitored at 6, 9, and 12 months.

Advanced urothelial cancer has no cure. But only a few chemotherapy drugs have been tested for it. The Co-eXpression ExtrapolatioN (COXEN) model predicts if cells respond to treatment. It may also help determine which drugs fight urothelial cancer based on the characteristics of a tumor. Researchers want to test if this model can choose the best therapy for advanced urothelial cancer within 3 weeks and how tumors respond to the next best therapy.

Patients will receive one of 75 FDA approved chemotherapies or targeted therapies based on the results of individual tumor testing.

A multi center, open-label, Phase 1 dose escalation study with expansion cohort is designed to determine the maximum tolerated dose, recommended phase II dose, and dosing schedule of PRS-343 (a type of targeted therapy) in patients with HER2+ advanced or metastatic solid tumors, including bladder cancer. PRS-343 will be administered by intravenous (IV) infusion every 3 weeks initially. If safety data suggest a different dosing schedule should be evaluated, dosing every 2 weeks or every 4 weeks in a 28-day cycle may be conducted.

In this four part study, NKTR-214 (a type of immunotherapy) will be administered in combination with nivolumab (Opdivo, a type of immunotherapy) in Parts 1 & 2, and with nivolumab and ipilimumab (Yervoy, a type of immunotherapy) in Parts 3 & 4. In Part 1, the safety, effectiveness and recommended dose of NKTR-214 in combination with nivolumab will be determined. In Part 2, the clinical benefit, safety, and tolerability of combining NKTR-214 with nivolumab Renal Cell Carcinoma and Urothelial Carcinoma. In Part 3, the safety, effectiveness and dose level of NKTR-214 in combination with nivolumab and ipilimumab will be determined. In Part 4, the clinical benefit, safety, and tolerability of the combination of all three drugs will be evaluated in select patients with renal cell carcinoma. All three drugs target the immune system and may act together to promote anti-cancer effects. This study has 2 arms: All drugs are given intravenously (IV) in clinic. Arm A: Combination of NKTR-214 + nivolumab Part 1: Patients with select tumor types will receive NKTR-214 doses administered either once every 2 weeks or once every 2 weeks, in combination with 360 mg of nivolumab once every 3 weeks or 240 mg nivolumab once every 2 weeks. Part 2: Additional patient cohorts with select tumor types will be dosed at the dose/schedule of NKTR-214 and nivolumab (as determined by Part 1 of the trial). Arm B: Combination of NKTR-214 + nivolumab + ipilimumab Part 3: The first schedule to be evaluated, Cohort A, is NKTR-214 0.006 mg/kg and nivolumab 360 mg once every 3 weeks with the addition of ipilimumab 1 mg/kg (kilogram, based on your weight) once every 6 weeks. Upon review of safety, tolerability, and other data collected in Cohort A, alternative doses/schedules may be considered where ipilimumab will be administered at a later cycle. Part 4: Additional patient cohorts with select tumor types will be dosed at the dose/schedule of NKTR-214 in combination with nivolumab and ipilimumab (as determined by Part 3 of the trial).

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.

Non-muscle-invasive bladder cancer is in the early stages, but it usually comes back after treatment. The drugs Vicinium (a type of targeted therapy) and Durvalumab (a type of immunotherapy) may help the immune system find and destroy cancer cells. The objective of this study is to test if the drugs Durvalumab and Vicinium together are safe and effective to treat people with bladder cancer that has not spread to the muscle in the bladder. All patients will receive: Durvalab 1500 mg administered intravenously (IV) once every 4 weeks for 12 months provided that the patient is tolerating therapy and remains free of recurrent bladder cancer. Durvalumab 1500 mg will then be administered intravenously once every 3 months to provide an immune boost. Vicinium is administered intravenously (IV) in a 12 week Induction Phase followed by a Maintenance Phase for at least one year with an option for a total of up to 2 years of treatment. During the Maintenance Phase, Vincinium is administered every other week. The dose of Vincinium 30mg in 50 mL of saline.

In this study, participants with high risk non-muscle-invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette Guerin (BCG) therapy (a type of chemotherapy instilled directly in to the bladder) and who are considered ineligible for or have refused to undergo radical cystectomy (total surgical removal of the bladder), will receive pembrolizumab therapy (a type of immunotherapy). It is thought that treatment with pembrolizumab will result in a clinically meaningful response. All participants will receive: Pembrolizumab 200 mg intravenously (IV) once every 3 weeks for up to 24 months.

Clinical trial to determine the efficacy (how well it works) of the Bladder EpiCheck (a type of urine test to check for bladder cancer cells) test compared to the gold standard cystoscopy (a thin tube with a camera and light on the end that is inserted through your urethra and into your bladder so the doctor can see the inside of your bladder) and pathology (looking at cell taken from your bladder under a microscope) in patients under monitoring for recurrence of bladder cancer.

Patients will be enrolled in one of two arms:

Arm A: Bladder EpiCheck Urine Test

The Bladder EpiCheck test is a diagnostic device for the detection of bladder cancer. It is intended for use as a noninvasive method for monitoring for tumor recurrence in conjunction with cystoscopy inpatients previously diagnosed with bladder cancer.

Arm B: Cystoscopy and pathology (standard of care)

Routine cystoscopy for bladder cancer recurrence and pathology confirmation for patients with positive cystoscopy.

This study will determine whether Synergo® RITE (a type of themochemotherapy) + Mitomycin C (a type of chemotherapy) treatment is effective as second-line therapy for cancer that is only in the bladder (CIS or carcinoma in situ) NMIBC (non-muscle invasive bladder cancer) BCG (a type of chemotherapy) unresponsive patients with or without papillary NMIBC, through examination of the complete response rate (CRR, meaning all evidence of the cancer is gone) and disease-free duration for complete responders. The study will also explore progression-free survival time (there is still evidence of the cancer, but it is not growing or spreading), bladder preservation rate (meaning you do not need surgical removal of the bladder due to the cancer), and overall survival time. The study will address an unmet need to identify a treatment effective in both ablating (destroying) the cancer and providing a prolonged disease-free period for patients. Ideally, the treatment will delay progression to invasive disease, thus preserving the bladder. The protocol has 1 arm: Synergo® RITE + MMC (Mitomycin C) Bladder radiofrequency-induced hyperthermia will be delivered in combination with each instillation of MMC in accordance with the Sponsor operational guidelines. Details, including frequency of treatment, will be given prior to treatment. All treatment will be given in clinic.

This is a single arm Phase II study with a safety run-in to identify the recommended phase II dose of the combination therapy of atezolizumab (Tecentriq, a type of immunotherpy) and guadecitabine (a type of immunotherpay). Patients with recurrent/advanced urothelial carcinoma (stage IV) who had previously progressed on check-point inhibitor therapy (immunotherapy) with PD-1 or PD-L1 targeting agents are eligible for this study. After a dose that is safe and tolerable has been established, a dose expansion phase (Phase II) will begin. This study has 1 arm: Atezolizumab + Guadecitabine Patients will be administered atezolizumab intravenously on day 1 and day 22 of a 6 week cycle for 8 cycles. Guadecitabine will be administered subcutaneously (an injection into the fat just below the skin) on days 1 through 5 of the 6 week cycle for 4 cycles.

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 study evaluates the post-cystectomy (surgical removal of the bladder) CD8+ tumor response of patients receiving nivolumab (an immunotherapy) plus urelumab (an immunotherapy) versus nivolumab alone. It is hypothesized that giving these drugs together will improve patients’ response rates (increase anti-tumor activity) more than either drug given alone. Half the patients will receive nivolumab plus urelumab, while the other half will receive nivolumab alone. The study participants will have muscle invasive urothelial carcinoma of the bladder (MIBC) that is not suitable for cisplatin-based chemotherapy, but be fit to undergo surgical resection of their cancer by cystectomy. Patients with resectable clinical node positive disease within the true pelvis (N1) are eligible.

Nivolumab 240 mg will be administered by one-hour intravenous infusion on Day 1 and Day 15 for two cycles. Urelumab 8mg will be administered by one-hour intravenous infusion on Day 1 for two cycles.

The study is investigating the ability of UroGen's MitoGel procedure to treat urothelial carcinoma tumors from the upper urinary tract. If this treatment will prove to be effective this will lead to the development of a new treatment approach for patients suffering from Low Grade Upper Urinary Urothelial Carcinoma (UTUC).

MitoGel will be instilled directly into the bladder using a catheter. Treatment with MitoGel is given once weekly for a total of 6 treatments. Patients who will demonstrate complete response (meaning your cancer is no longer visible) will be treated with MitoGel once monthly as a maintenance therapy for a total of 11 treatments.

The purpose of this study is to determine if TAR-200 (GemRIS), an investigational drug-delivery system, is safe and tolerable in patients with muscle-invasive bladder cancer (MIBC) between diagnosis and radical cystectomy (RC). TAR-200 is a passive, non-resorbable (meaning it only acts locally in the bladder and will not be absorbed into the body) gemcitabine (Gemzar, a type of chemotherapy) releasing intravesical (in the bladder) drug delivery system, regulated as a drug, whose primary mode of action is the controlled release of gemcitabine into the bladder over a 7-day period.

There are two arms in this study:

Arm A: Patients who have residual disease after surgical removal of the bladder tumor (TURBT)

TAR-200 is placed into the bladder through a catheter on Study Day 0 and is removed on Study Day 7. TAR-200 releases gemcitabine gradually during the 7 day indwelling time. A second TAR-200 is placed in the bladder on Study Day 21 and is removed on Study Day 28, which is the day of the Radical Cystectomy (RC, surgery that removes the entire bladder).

Arm B: Patients who do NOT have residual disease after surgical removal of the bladder tumor (TURBT)

TAR-200 is placed into the bladder through a catheter on Study Day 0 and is removed on Study Day 7. TAR-200 releases gemcitabine gradually during the 7 day indwelling time. A second TAR-200 is placed in the bladder on Study Day 21 and is removed on Study Day 28, which is the day of the Radical Cystectomy (RC).

The purpose of this study is to evaluate the overall response rate (ORR, meaning how much the cancer decreases in size) of INCB054828 (a type of targeted therapy) as a monotherapy (given alone, not in combination with any other therapy) in the treatment of metastatic or surgically unresectable urothelial carcinoma harboring FGF/FGFR alterations (a specific genetic mutation).

INCB054828 is an oral drug taken once daily (at home) on a 2-weeks-on-therapy and 1-week-off-therapy schedule.

The aim of this study is to evaluate a risk-adapted approach to the treatment of muscle invasive bladder cancer. Each baseline transuretheral resection of bladder tumor (TURBT) sample will be sequenced while proceeding with neoadjuvant (prior to surgery) accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) chemotherapy. All of these drugs are types of chemotherapy. Based on the mutational profile and the post AMVAC TURBT findings, patients will be treated with active surveillance (experimental arm), or standard of care intravesicle (directly in the bladder) therapy, chemoradiation (chemotherapy + radiation) or surgery. We hypothesize that this approach will lead to non-inferior metastasis-free survival at 2 years, while preserving the bladder and thus quality-of-life for a proportion of patients. Patients on each arm of this study will have a TURBT procedure (TURBT #1), followed by MVAC chemotherapy. Each drug (methotrexate, vinblastine, doxorubicin and cisplatin) will be given intravenously (IV) on days 1 and 14 of each 28 day cycle for 3 cycles. Patient will then have a second TUBRT procedure (TRUBT #2). Patients will then receive 1 of 4 possible arms: Arm A: Chemoradiation followed by TURBT #3 Radiation: Intensity modulated radiation therapy (IMRT) 2.0 Gy per fraction to the whole bladder plus a margin for a total of 32 fractions (64.0 Gy). Radiation will be administered once daily from Monday to Friday. Chemotherapy: 5-FU (Fluorouracil) given continuously for 24 hours via intravenous infusion days 1-5 and 16-20 with radiation treatment + Mitomycin C given intravenously (IV) on day 1 only, with radiation treatment. Arm B: Active surveillance Patients will receive standard of care surveillance for recurrence of their bladder cancer. Arm C: Intravesicle therapy followed by TURBT#3 Patients will receive standard of care/provider preference intravesicle therapy. Arm D: Radical cystectomy Patients will receive standard of care radical cystectomy (complete surgical removal of the bladder).

The purpose of this study is to evaluate the safety, tolerability, and anti-tumor (anti-cancer) activity of the combination of durvalumab (Imfinzi, a type of immunotherapy) + tremelimumab (a type of immunotherapy) or durvalumab alone in different solid tumors. It is thought that combining these two drug together would be more effective than durvalumab alone.

Patients will be assigned to one of two arms: each cycle is 4 weeks

Arm A Combination Therapy

Durvalumab 1,500 mg + tremelimumab 75 mg will be given intravenously (IV, in clinic) once every 4 weeks for up to a maximum of 4 doses (or cycles) followed by durvalumab 1,500 mg IV alone once every 4 weeks.

Arm B Monotherapy

Durvalumab 1,500 mg given IV (in clinic) once every 4 weeks.

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.

This study will test how an experimental drug (enfortumab vedotin) affects patients with cancer of the urinary system (urothelial cancer). This type of cancer includes cancer of the bladder, renal pelvis, ureter or urethra that has spread to nearby tissues or to other areas of the body.

The study will enroll patients who were previously treated with a kind of anticancer drug called an immune checkpoint inhibitor (CPI, immunotherapy). Some CPIs have been approved by the FDA for the treatment of urothelial cancer. The study will test if the cancer shrinks with treatment (effectiveness). The study will also look at the side effects of the drug (safety).

Patients will receive enfortumab vedotin intravenously (IV, given in clinic) on days 1, 8 and 15 of every 28 day cycle.

This pilot phase II trial studies how well sapanisertib (a type of targeted therapy) works in treating patients with bladder cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic) with tuberous sclerosis (TSC)1 and/or TSC2 mutations (changes in deoxyribonucleic acid [DNA]). Sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The study has 1 arm: Sapanisertib Patients receive sapanisertib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

This randomized phase II trial studies how well cisplatin (a type of chemotherapy) and gemcitabine hydrochloride (a type of chemotherapy) with or without ATR kinase inhibitor VX-970 (a type of targeted therapy) works in treating patients with urothelial cancer that has spread to other places in the body (metastatic disease). Drugs used in chemotherapy, such as cisplatin and gemcitabine hydrochloride, 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. ATR kinase inhibitor VX-970 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known if cisplatin and gemcitabine hydrochloride work better alone or with ATR kinase inhibitor VX-970 in treating patients with urothelial cancer. The study has 2 arms: Arm A: VX-970 + gemcitabine hydrochloride + cisplatin; 1 cycle = 21 days Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8, and cisplatin IV over 60 minutes on day 1. Patients also receive ATR kinase inhibitor VX-970 IV over 60 minutes on days 2 and 9. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm B: Gemcitabine hydrochloride + cisplatin; 1 cycle = 21 days Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and cisplatin IV over 60 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

This randomized phase III trial studies Tokyo-172 strain bacillus Calmette-Guerin (BCG) solution with or without a vaccination using Tokyo-172 strain BCG to see how well it works compared with TICE BCG solution in treating patients with bladder cancer that has not spread to muscle. BCG is a non-infectious bacteria that when instilled into the bladder may stimulate the immune system to fight bladder cancer. Giving different versions of BCG with vaccine therapy may prevent bladder cancer from returning. The study has 3 arms: Arm I: BCG solution (standard of care) INDUCTION: Patients receive TICE BCG solution intravesically (directly in the bladder) once a week for 6 weeks. MAINTENANCE: Patients receive TICE BCG solution intravesically once a week for 3 consecutive weeks at months 3, 6, 12, 18, 24, 30, and 36 for up to 7 doses. Arm II: Tokyo-172 strain BCG solution INDUCTION: Patients receive Tokyo-172 strain BCG solution intravesically once a week for 6 weeks. MAINTENANCE: Patients receive Tokyo-172 strain BCG solution once a week for 3 consecutive weeks at months 3, 6, 12, 18, 24, 30, and 36 for up to 7 doses. Arm III: Tokyo-172 strain BCG solution with priming (priming may help treatment work better) PRIME: Patients receive Tokyo-172 strain BCG vaccine once intradermally (injected just under the top layers of skin). INDUCTION: Within 21 days, patients receive Tokyo-172 strain BCG solution as in Arm II. MAINTENANCE: Patients receive Tokyo-172 strain BCG solution as in Arm II.

CRLX101 consists of a sugar molecule cyclodextrin linked to a chemotherapy drug called camptothecin. The combined molecule or nanoparticle drug travels through the blood. Once inside cancer cells, the chemotherapy drug is released from the molecule. Olaparib (a type of targeted therapy, a PARP inhibitor) is a drug that may stop cancer cells from repairing the DNA damage caused by chemotherapy. Researchers want to see how safe it is to give CRLX101 and olaparib together and to see how well the combination treats specific types of cancer. Patients will receive the two study drugs in 28 day cycles (1 cycle = 28 days). CRLX 101 will be given intravenously (IV) on days 1 and 15 and the olaparib will be taken by mouth days 3-13 and 17-26.

This is a single-arm, phase 1/2a study of formulated paclitaxel (a type of chemotherapy) in subjects with low-grade, noninvasive papillary carcinoma (stage Ta) of the bladder. Part 1 of the study will enroll 6 subjects (3 per cohort) with low-grade, stage Ta transitional cell carcinoma (TCC) of the bladder who will receive escalating doses of paclitaxel formulated as TSD-001 every 2 weeks for 6 treatments. Part 2 of the study will enroll an additional 10 subjects with low-grade, stage Ta (multifocal) TCC of the bladder who will receive weekly TSD-001 for 6 weeks at the highest nontoxic dose established in part 1 of the study. This study has 3 arms: Arm 1: Experimental: TSD-001 Administration Part 1, Cohort 1 For the first 3 subjects enrolled, the initial dose of TSD-001 will be 10 mg in Sterile Water for Injection (SWFI) directly into the bladder. TSD-001 will be retained in the bladder for 2 hours (1 hour or more will be acceptable, depending on subject's tolerability of the procedure). Dosing will be titrated up based on adverse effects and tolerability. Arm 2: Experimental: TSD-001 Administration Part 1, Cohort 2 For the next 3 subjects enrolled, the initial dose will be 150 mg in SWFI. TSD-001 will be retained in the bladder for 2 hours (1 hour or more will be acceptable, depending on subject's tolerability of the procedure). Dosing will be titrated up to 600 mg, based on adverse effects and tolerability. Arm 3: TSD-001 Administration Part 2 The maximum tolerated dose established in part 1 will be given weekly via the intravesical route (instilled directly into the bladder).

This is a Phase I/IIA, open-label, multi-center trial to evaluate the safety, immunogenicity (the ability to cause a response of the immune system) and preliminary clinical effectiveness of INO-5401 + INO-9012 (both types of immunotherapy) delivered by intramuscular (IM) injection followed by electroporation (EP, this involves the application of brief electric pulses to tissue, using the CELLECTRA 2000 device, in order to make cell membranes more permeable, allowing more drug into the cell. This is temporary and reversible.), in combination with atezolizumab (Tecentriq, a type of immunotherapy) in participants with locally advanced unresectable or metastatic/recurrent Urothelial Carcinoma (UCa). The trial population is divided into two cohorts: Cohort A: Participants with locally advanced unresectable or metastatic/recurrent UCa, who have confirmed disease progression during or following treatment with anti-Programmed Death receptor-1/Programmed Death receptor Ligand-1 (anti-PD-1/PD-L1) therapy (immunotherapy); Cohort B: Participants with locally advanced unresectable or metastatic/recurrent UCa, who are treatment naïve and ineligible for cisplatin-based chemotherapy. Both cohorts are treated with INO-5401 and INO-9012 in combination with atezolizumab. INO-5401 is given as a 9 mg IM injection. INO-9012 is given as a 1 mg IM injection. INO-5401 + INO-9012 will be administered as an IM injection, followed by EP using a CELLECTRA® 2000 device every 3 weeks for 4 doses, then every 6 weeks for 6 additional doses, then every 12 weeks. Atezolizumab will be administered by intravenous (IV) infusion every 3 weeks.

This is a single arm open label multi-institutional phase II trial of olaparib (a type of targeted therapy, a PARP inhibitor) monotherapy in subjects with metastatic urothelial cancer that has DNA damage response (DDR) alterations (specific genetic changes in the tumor cells). The primary objective of the study is to estimate the objective response rate (measurable on radiographic imaging) to treatment with olaparib. The study has 1 arm: Olaparib monotherapy (olaparib only). Each cycle is 28 days. Olaparib is taken by mouth (orally or PO) at either 300 mg or 200 mg twice daily, based on kidney function tests.

The purpose of this study is to evaluate efficacy of erdafitinib (a type of targeted therapy) versus chemotherapy or pembrolizumab (a type of immunotherapy) in participants with advanced urothelial cancer harboring selected fibroblast growth factor receptor (FGFR) aberrations (a particular genetic mutation in cancer cells) who have progressed after one prior treatment. It will consist of screening, treatment phase, and post-treatment follow-up. The study has 2 treatment arms: 1 cycle = 21 days Arm A: for participants treated with prior immunotherapy Erdafitinib + Vinflunine OR Docetaxel (both are types of chemotherapy) Erdafitinib tablets are taken by mouth (orally or PO) at a dose of 8 mg, once daily. Vinflunine 320 mg/m2 is given as a 20 minute intravenous (IV) infusion once every 3 weeks. Docetaxel 75 mg/m2 is given as a 1 hour IV infusion every 3 weeks. Treatment with either agent is the choice of the treating physician. Arm B: for participants NOT treated with prior immunotherapy Erdafitinib + Pembrolizumab Erdafitinib tablets are taken by mouth at a dose of 8 mg, once daily. Pembrolizumab 200 mg as a 30 minute IV infusion once every 3 weeks.