Bladder Cancer Trials

This phase II trial studies how well treatment that is directed by genetic testing works in patients with solid tumors that have progressed following at least one line of standard treatment, or for which no standard treatment exists. Genetic tests look at the unique genetic material (genes) of a patient’s tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may be more likely to benefit from treatment that targets their tumor's particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors.

Patients must either:

1. Undergo a biopsy, along with molecular characterization of the biopsy material for specific, pre-defined mutations, amplifications, or translocations. Patient must have a tumor that is amenable to an image-guided or directly visible biopsy, and the biopsy must not be considered to be more than a minimal risk to the patient.

2. Have formalin-fixed paraffin-embedded tumor tissue block(s) available for submission that have been collected within six months prior to pre-registration.

3. Have results from a designated outside laboratory that indicate a "rare variant" that is an actionable mutation of interest.

Consenting patients also undergo collection of blood samples for research purposes.

Treatment recommendations will vary depending on tumor type and results of genetic testing. Specific eligibility for treatment based on genetic testing will also vary.

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 comprehensive genomic (genes) analysis and biospecimen (tumor tissue) repository study incorporates Next Generation Sequencing (NGS) of archival tumor tissue from 200 subjects with metastatic urothelial cancer in support of several goals. The immediate goal involves generation of a comprehensive report identifying subject specific genetic mutations and/or alterations based on NGS. Additionally, DNA and RNA extracted from tumor specimens and any remaining blocks/slides from the NGS will be stored for future research. Long-term, the goal of this endeavor is to support collaborative research projects in metastatic urothelial cancer by allowing investigators to study coded (meaning anonymous) clinical data linked to data from biospecimen (tumor tissue) studies.

No treatment will be given in this study.

This study is designed to test the efficacy of the immunotherapy pembrolizumab when given closely following chemotherapy. Pembrolizumab blocks the component of the tumor cell that allows tumors to grow unencumbered. In doing this, pembrolizumab simultaneously signals the immune system to kill the tumor cells. Participants eligible for this study must have undergone 4-6 cycles of chemotherapy no more than 2-6 weeks prior to starting this study. The progression-free survival rate will be evaluated between patients who received pembrolizumab following chemotherapy and patients who only received chemotherapy. Participants will be randomly separated into two treatment groups. Patients in both groups will receive injections every three weeks for up to two years or until disease progression. However, one group will be receiving injections of an inactive agent, in this case saline, and the other group will be receiving pembrolizumab injections. To eliminate bias patients will remain unaware of which treatment group they are in.

This trial is designed to compare the tumor response between two different dosing regimens of JNJ-42756493. JNJ-42756493 is a targeted therapy that interrupts cancer cell signaling in a way that inhibits tumor cell proliferation and causes tumor cell death. Persons eligible for this study must have metastatic or unresectable bladder cancer. Participants will be randomly separated into two treatments groups, each with a different regimen of oral JNJ-42756493. Treatment cycles will span 28 days. Group one will take JNJ-42756493 once daily every day for one week followed by one week without taking any JNJ-42756493, continuing in this fashion. Group two will take JNJ-42756493 once daily every day.

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 is a phase I/Ib, open-label, safety, and pharmacodynamics (how the drug works in the body) study of pembrolizumab (an immunotherapy) in combination with vorinostat (a targeted therapy) in patients with advanced renal or urothelial cell carcinoma. It is hypothesized that giving these drugs together will improve patients’ response rates (increase anti-tumor activity) more than either drug given alone.

This clinical study will consist of a Dose Finding Phase and an Expansion Phase. The Dose Finding Phase will estimate the Recommended Phase II Dose in patients with advanced renal and urothelial cell carcinoma. The Dose Finding Phase will lead to the identification of an Expansion Test Dose (the highest tested dose that is declared safe and tolerable by the investigators and sponsor) for pembrolizumab in combination with vorinostat.

Patients will be treated with oral vorinostat every day for 14 days (taken at home) and with pembrolizumab at the fixed dose of 200 mg IV (given in the clinic) once every 21 days. Each cycle is 21 days. Two dose levels of vorinostat will be tested, 100 mg and 200 mg.

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 study is designed to test how effective the combination of ramucirumab and docetaxel is at lengthening progression-free survival in patients with urothelial cancer. Docetaxel is a chemotherapy drug that halts cancer cell division, leading to cancer cell death. Ramucirumab is an immunotherapy agent that blocks one of the cancer's methods for synthesizing blood vessels. Blocking this prevents adequate blood supply to the cancer, which slows tumor growth. Persons eligible for this trial must have failed prior platinum-based chemotherapy. Participants will be randomly separated into two treatment groups. Both groups will receive IV treatments in 21-day cycles. For the standard treatment group, this IV treatment consists of standard docetaxel plus an inactive agent. For the experimental group, this IV treatment consists of standard docetaxel plus ramucirumab. Participants will not know whether they are receiving the inactive agent or the ramucirumab.

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.

Cancer treatments that couple pharmacological (drug) activation of tumor antigen presentation with activation and expansion of CD8+ T and natural killer (NK) cells in the tumor environment have the potential to induce an effective anti-tumor immune response in patients. NKTR-262 is a type of immunotherapy. In preclinical studies, a single intratumoral (directly into the tumor) injection of NKTR-262 plus intravenous (IV) NKTR-214 (a type of immunotherapy) resulted in shrinkage of cancer, including outside of the original tumor that was injected. Preliminary clinical data show NKTR-214 plus nivolumab (a type of immunotherapy) enhances immune-stimulatory responses. This trial will assess safety and anti-tumor activity of NKTR-262 with NKTR-214 +/- nivolumab for the treatment of selected cancers, including kidney cancer and urothelial cancer. This study has 2 arms: All doses of study medication will be given in clinic. Arm A: NKTR-262 + NKTR-214 Phase 1 Doublet: NKTR-262 in escalating doses, will be combined with NKTR-214. The goal of this dose escalation part of the study is to establish a safe and tolerable recommended phase 2 dose (RP2D) for NKTR-262 in combination with NKTR-214 in a once every 3 week fixed dose. Phase 2 Doublet: NKTR-262 RP2D will be combined with a once every 3 week dose of NKTR-214 in select tumor indications (including kidney cancer and urothelial cancer) to evaluate anti-tumor activity and to obtain additional safety data. Patients may be discontinued from receiving study treatment based on the results of disease assessments or if experiencing intolerable side effects. Arm B: Triplet: NKTR-262 + NKTR-214 + Nivolumab Phase 1 Triplet: The RP2D of NKTR-262 RP2D will be combined with a once every 3 week dose regimen of NKTR-214 plus nivolumab. The goal of this arm is to establish the safety and tolerability of the triplet. Phase 2 Triplet: The RP2D of NKTR-262 will be combined with a once every 3 week dose regimen of NKTR-214 plus nivolumab in select tumor indications to evaluate anti-tumor activity and to obtain additional safety data. Patients may be discontinued from receiving study treatment based on the results of disease assessments or if experiencing intolerable 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.

The purpose of this study is to determine the effectiveness and safety of pembrolizumab (an immunotherapy) with or without chemotherapy versus chemotherapy alone in patients with advanced or metastatic urothelial carcinoma (bladder cancer). The primary hypothesis is that pembrolizumab plus chemotherapy is superior to chemotherapy alone for progression-free survival and overall survival.

Participants receive either:

1. Pembrolizumab 200 mg intravenously (IV) on Day 1 of each three-week cycle for a maximum of 35 doses, OR

2. Pembrolizumab 200 mg IV on Day 1 of each three-week cycle for a maximum of 35 doses PLUS chemotherapy with EITHER

a. Cisplatin 70 mg/meter squared IV on Day 1 (or Day 2 if required per local guidelines) of each three-week cycle PLUS gemcitabine IV infusion 1,000 mg/metered squared on Day 1 and Day 8 of each three-week cycle, OR

b. Carboplatin area under the curve 5 (AUC 5) (or AUC 4.5 if required per local guidelines) IV on Day 1 (or Day 2 if required per local guidelines) of each three-week cycle PLUS gemcitabine 1,000 mg/meter squared IV on Day 1 and Day 8 of each three-week cycle.

Previous multi-dose phase I and phase II clinical studies have demonstrated that Instiladrin (a type of immunotherapy) is a safe and effective treatment for BCG-refractory and recurrent NMIBC (non-muscle invasive bladder cancer or superficial bladder cancer). This phase III study is designed to expand those observations using a high dose of INSTILADRIN in patients who are "BCG unresponsive," which refers to patients with high-grade NMIBC who are unlikely to benefit from and should not receive further intravesical BCG (administered directly in to the bladder with a catheter). It is hypothesized that these patients will respond to (benefit from) Instiladrin.

Instiladrin is administered into the bladder and held for one hour. It is given once every three months. After the first treatment, patients have a cystoscopy (a flexible scope inserted into the bladder) and a urine cytology exam is conducted (patient gives a urine sample) around two weeks before each subsequent treatment to assess efficacy to determine if patients should continue on study. Patients may remain on study for up to two years.

This phase Ib/II study is designed to assess the safety, tolerability, pharmacokinetics, immunogenicity, patient-reported outcomes, and preliminary anti-tumor activity of atezolizumab (an immunotherapy) administered by intravenous (IV) infusion alone or in combination with intravesical BCG (chemotherapy administered directly in to the bladder with a catheter) in high-risk non-muscle invasive bladder cancer or superficial bladder cancer (NMIBC) patients. It is hypothesized that giving these drugs together will improve patients’ response rates (increase anti-tumor activity) more than either drug given alone.

Dose levels and frequency of treatment/clinic visits vary depending on which arm of the study patients are assigned to.

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 safety and pharmacokinetics (how a drug works in the body) ASG-22CE (a type of targeted therapy) as well as assess the immunogenicity (the ability to cause the immune system to respond) and antitumor activity in subjects with metastatic urothelial cancer and other malignant solid tumors.

All subjects will receive a single 30 minute intravenous (IV) infusion (in clinic) of ASG-22CE once weekly for 3 weeks of every 4 weeks (on Days 1, 8, and 15). Each cycle is 4 weeks. Dose levels will vary.

All subjects will be followed post-treatment every 2 months either in person or by telephone contact to obtain information on disease progression and death.

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 determine how patients with locally advanced or metastatic urothelial carcinoma respond to treatment with rucaparib (a type of targeted therapy, a PARP inhibitor). The study has 1 arm: Rucaparib monotherapy Rucaparib is taken by mouth (orally, PO) daily.

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.