Symptoms and General Pathology

All Conditions

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Death

Carcinoma

Small Cell Lung Carcinoma

Adenocarcinoma

Carcinoma, Transitional Cell

Carcinoma, Squamous Cell

Carcinoma, Small Cell

Urinary Bladder Neoplasms

Carcinoma, Medullary

Lung Neoplasms

Penile Neoplasms

Thyroid Neoplasms

Thyroid Diseases

Carcinoma, Neuroendocrine

Urologic Neoplasms

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Genital Neoplasms, Male

Genital Diseases

Genital Diseases, Male

Penile Diseases

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Endocrine System Diseases

Kidney Diseases

Small Cell Lung Cancer

Transitional Cell Carcinoma

Penile Cancer

Thyroid Cancer, Medullary

Renal Medullary Carcinoma

Small Cell Carcinoma of the Bladder

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Atezolizumab

Irinotecan

Sacituzumab govitecan

Immunomodulating Agents

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Immunoconjugates

Immunologic Factors

Treatment with sacituzumab govitecan and atezolizumab

Sacituzumab govitecan is administered IV at 10 mg/kg on days 1 and 8 of each 21-day cycle.

Atezolizumab is administered IV at 1200 mg on day 1 each 21-day cycle.

Lisa Ley, R.N.

Andrea B Apolo, M.D.

Lisa Ley

Background:

Rare tumors of the genitourinary (GU) tract can appear in the kidney, bladder, ureters, and penis. Rare tumors are difficult to study because there are not enough people to conduct large trials for new treatments. Two drugs-sacituzumab govitecan (SG) and atezolizumab-are each approved to treat other cancers. Researchers want to find out if the two drugs used together can help people with GU.

Objective:

To test SG, either alone or combined with atezolizumab, in people with rare GU tumors.

Eligibility:

Adults aged 18 years and older with rare GU tumors. These may include small cell carcinoma of the bladder; squamous cell carcinoma of the bladder; primary adenocarcinoma of the bladder; renal medullary carcinoma; or squamous cell carcinoma of the penis.

Design:

Participants will be screened. They will have a physical exam with blood and urine tests. They will have tests of heart function. They will have imaging scans. They may need a biopsy: A small needle will be used to remove a sample of tissue from the tumor.

Both SG and atezolizumab are given through a tube attached to a needle inserted into a vein in the arm.

All participants will receive SG on days 1 and 8 of each 21-day treatment cycle. Some participants will also receive atezolizumab on day 1 of each cycle.

Blood and urine tests, imaging scans, and other exams will be repeated during study visits.

Treatment may continue for up to 5 years.

Follow-up visits will continue for 5 more years.

Background:

* Urothelial carcinoma (UC) represents the most common histology for tumors of the bladder and urinary tract.
* A minority of patients have primary tumors of the bladder/urinary tract consisting of rare histological variants, including small cell carcinoma, primary adenocarcinoma of the bladder (urachal or non-urachal), or squamous cell carcinoma. Some tumors may contain elements of UC mixed with these variants or may be entirely composed of such variants.
* Clear cell renal cell carcinoma (ccRCC) is the most common histology for cancers of the renal parenchyma. Renal medullary carcinoma is a rare histology of kidney cancer, which is associated with sickle cell trait and other hemoglobinopathies.
* Rare tumors of the genitourinary (GU) tract often have more aggressive clinical course, but lack standard of care treatment regimens, since these patient populations are poorly represented or excluded from most clinical trials.
* Sacituzumab govitecan (SG) is an antibody-drug conjugate of an IgG 1 monoclonal antibody targeting trophoblastic cell surface antigen 2 (Trop2) with a chemotherapeutic payload of SN-38. SN-38 is an active metabolite of irinotecan and acts as a topoisomerase I inhibitor.
* SG has demonstrated clinical activity in solid tumors. In phase II clinical trials, SG has demonstrated efficacy in metastatic UC after progression on platinum-based chemotherapy and immune checkpoint inhibitor (ICI) therapy.
* Atezolizumab is an anti- programmed death-ligand 1 (PD-L1) ICI that is approved for advanced/metastatic UC in patients ineligible to receive platinum therapy.
* There are currently no clinical trials for SG monotherapy or SG/atezolizumab combination in rare GU tumors.

Objective:

-To determine clinical efficacy of sacituzumab govitecan (SG), either alone or in combination with atezolizumab, as defined by objective response rate (ORR), in participants with rare metastatic non-prostate genitourinary tumors

Eligibility:

* Age \>= 18 years
* ECOG performance status \<= 1
* Histologically confirmed diagnosis of locally advanced (unresectable) or metastatic GU tumors of the following histologies: small cell carcinoma, squamous cell carcinoma, or primary adenocarcinoma of the bladder or urinary tract; or renal medullary carcinoma or squamous cell carcinoma of the penis.
* Participants must have locally advanced unresectable or metastatic disease on cross-sectional imaging.
* Participants may have received any prior programmed cell death protein 1 (PD-1)/PD-L1 axis ICI treatment.

Design:

* This is an open label, non-randomized phase II trial with two arms.
* All participants will receive SG.
* Participants without prior treatment with any PD-1/PD-L1 axis ICI (checkpoint inhibitor na(SqrRoot) ve) will be eligible to receive concurrent atezolizumab.
* SG will be administered intravenously (IV) at 10 mg/kg on D1 and D8 of 21-day cycles.
* Atezolizumab will be administered IV at 1200mg on D1 of 21-day cycles.
* Treatment will be given in 21-day cycles continuously for a maximum of 5 years, or until signs of progression or intolerable side effects.
* The accrual ceiling will be set at 60 to allow for inevaluable participants and screen failure.

Sacituzumab Govitecan With or Without Atezolizumab Immunotherapy in Rare Genitourinary Tumors (SMART) Such as Small Cell, Adenocarcinoma, and Squamous Cell Bladder/Urinary Tract Cancer, Renal Medullary Carcinoma and Penile Cancer

A Phase II Study of Sacituzumab Govitecan With or Without Atezolizumab Immunotherapy in Rare Genitourinary Tumors (SMART) Such as Small Cell, Adenocarcinoma, and Squamous Cell Bladder/Urinary Tract Cancer, Renal Medullary Carcinoma and Penile Cancer

Percentage of participants by best overall response (e.g., CR, PR, SD,PD) to therapy

Time from start of treatment to disease progression or death in participants who achieve CR or PR

Time from the start of treatment that participants are still alive.

Duration of time from start of treatment to time of progression or death, whichever occurs first

Percentage of participant who have achieved CR, PR, and SD while on treatment.

Adverse events (AEs) will be reported by type and grade of toxicity

National Cancer Institute (NCI)

Neoplasm Metastasis

Prophylactic cranial irradiation (PCI) treatments to be started within 4 months after the end of chemotherapy or surgery to a total dose of 30 Gy, given at 2 Gy per fraction, 5 days per week for 3 weeks. On the first day of each week of therapy, a brain X-ray will done to see if the radiation is being given to the best area.

Prophylactic cranial irradiation (PCI) treatments to be started within 4 months after the end of chemotherapy or surgery to a total dose of 30 Gy, given at 2 Gy per fraction, 5 days per week for 3 weeks.

Prophylactic Cranial Irradiation (PCI)

On the first day of each week of therapy, a brain X-ray will done to see if the radiation is being given to the best area.

Brain X-ray

Seungtaek Choi, MD

The goal of this clinical research study is to learn if whole brain radiation can lower the chances of developing brain tumors in patients with small cell carcinoma of the urinary tract, including the bladder. The safety of whole brain radiation will also be studied.

Pregnancy Test:

Women who are able to have children must have a negative urine pregnancy test to be eligible for this study.

MRI/CT Scans:

Within six (6) weeks before having whole brain radiation, you will have a magnetic resonance imaging (MRI) or a computed tomography (CT) scan of your brain to check if brain tumors have developed.

Simulation Visit:

Before the radiation therapy begins, you will have a "simulation visit" to plan for the radiation therapy. During this session, you will be fitted to a plastic mask to hold your head still during radiation. The mask is made of a material called "thermoplastic" that becomes soft when it is placed in warm water. While this plastic is soft, it will be pulled over your face to make a mold. When the plastic cools down, it will harden again and the mask will be completed. After the mask is made, a CT scan of your head will be done for treatment planning.

Radiation Therapy:

You will begin radiation within 1 week after the simulation visit. You will have radiation visits Monday through Friday for 3 weeks (15 total therapy visits). Each therapy session will last about 15 minutes. It will take the study staff about 10 minutes to position you on the table and put the mask on. The radiation will be given over 2-3 minutes.

On the first day of each week of therapy, you will have a brain X-ray to see if the radiation is being given to the best area.

Follow-Up:

After the radiation therapy, you will have an MRI or a CT scan of the brain every 6 months for 1 year and then every year for 5 years to check the status of the disease. More frequent scans will be performed if your doctor thinks they are needed. You will also complete a written mental status exam with your doctor every 3-6 months for 2 years and then every year for 5 years. The exam will have a series of tests to check your memory and ability to follow instructions. The test will take about 15 minutes to complete.

Length of Study:

You may remain on study for as long as you are benefitting. You will be taken off study if your disease gets worse or if intolerable side effects occur.

This is an investigational study. The use of radiation to check for brain tumors before they have formed is investigational.

Up to 30 patients will take part in this study. All will be enrolled at MD Anderson.

Prophylactic Cranial Irradiation (PCI) for Small Cell Carcinoma of the Urothelium

Prophylactic Cranial Irradiation (PCI) for Patients With Small Cell Carcinoma of the Urothelium

Primary outcome for this trial is the rate of development of brain metastasis by 12 months following start of treatment. A "success" defined as a patient not developing brain metastasis by 12 months following start of treatment. After radiation therapy, participant has an MRI or a CT scan of the brain every 6 months for 1 year.

M.D. Anderson Cancer Center

Avelumab

Treatment with lurbinectedin and avelumab

Lurbinectedin is administered IV over 1 hour at 3.2 mg/m2 on day 1 of each 21-day cycle

Lurbinectedin

Avelumab is administered IV at 800 mg over 1 hour on day 1 of each 21-day cycle

NCIMO Referral Office

National Cancer Institute Referral Office

Background:

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 and avelumab are drugs that are approved to treat other cancers. Researchers want to see if these drugs can help people with SCCB or HGNET.

Objective:

To test lurbinectedin with or without avelumab in people with SCCB or HGNET.

Eligibility:

Adults aged 18 years and older with SCBB or HGNET that returned and spread after treatment.

Design:

Participants will be screened. They will have a physical exam. They will have blood tests and imaging scans. They may need to have a new biopsy: A small needle will be used to collect a tissue sample from the tumor.

Both study drugs are given through a tube attached to a needle inserted into a vein. If participants have already received a drug like avelumab they will receive only lurbinectedin. If patients have not been previously treated with a drug like avelumab they will receive both lurbinectedin and avelumab. All participants will receive their treatment once every 3 weeks for up to 10 years. They will also receive other drugs to relieve adverse effects.

Biopsies, blood tests, and imaging scans will be repeated during some study visits. Participants may also have urine tests and tests of their heart function.

Participants may remain in the study as long as the treatment is helping them. If they stop treatment, they will have safety visits 14, 30, and 90 days after their last dose. Additional follow-up visits will continue 5 to 10 years.

Background:

* Small cell carcinoma of the bladder (SCCB) is a rare, aggressive form of bladder cancer, accounting for less than 1% of all bladder malignancies.
* High grade neuroendocrine tumors (HGNET) of the urinary tract are very rare and include both small cell neuroendocrine carcinomas (SCNEC) and large cell neuroendocrine carcinomas (LCNEC).
* Traditionally regimens drawn from the small cell lung cancer literature (cisplatin and etoposide) are used in the frontline setting, and while initially highly responsive to chemotherapy, responses are generally short lived.
* There is little evidence to guide therapeutic decisions at time of disease progression.
* Lurbinectedin is a selective inhibitor of oncogenic transcription that binds preferentially to guanines located in the GC-rich regulatory areas of DNA gene promoters.
* Lurbinectedin prevents binding of transcription factors to their recognition sequences, inhibiting oncogenic transcription and leading to tumor cell apoptosis.
* Lurbinectedin was recently approved as a second line agent in small cell lung cancer, where it has shown an overall response rate of 35%.
* Immune checkpoint inhibitors have become part of the standard of care for small cell lung cancer, and their use in the community for treatment of SCCB has increased.
* However, immune checkpoint inhibitor use in SCCB is still case reportable in the literature, and no prospective studies have been published to date.

Objective:

-To assess the objective response rate (ORR) 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

Eligibility:

* Age \>= 18 years
* Histologically confirmed diagnosis of metastatic SCCB or HGNET of the urinary tract
* Participants must have metastatic disease defined as new or progressive lesions.
* Participants must have at least one measurable site of disease
* Participants must have received, be ineligible, or refused prior platinum/etoposide chemotherapy for SCCB or HGNET of the urinary tract.

Design:

* This is a Phase II, multisite, open label, nonrandomized study with two cohorts.
* All participants will receive lurbinectedin.
* Participants without prior immune checkpoint inhibitor exposure will be eligible to receive concurrent avelumab.
* Treatment will be given in 21-day cycles continuously for up to 10 years or until signs of progression or intolerable side effects.
* Lurbinectedin will be administered intravenously (I.V.) at 3.2mg/m\^2 every 21 days.
* Avelumab will be administered I.V. at 800mg every 21 days.
* The accrual ceiling will be set at 35 to allow for a small number of inevaluable participants.

Lurbinectedin With or Without Avelumab in Small Cell Carcinoma of the Bladder (LASER)

A Phase II Study of Lurbinectedin With or Without Avelumab in Small Cell Carcinoma of the Bladder (LASER)

Percentage of participants by best overall response (e.g., CR, PR, SD, PD) to therapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Sacituzumab Govitecan With or Without Atezolizumab Immunotherapy in Rare Genitourinary Tumors (SMART) Such as Small Cell, Adenocarcinoma, and Squamous Cell Bladder/Urinary Tract Cancer, Renal Medullary Carcinoma and Penile Cancer	NCT06161532	Small Cell Carc... Small Cell Carc... Squamous Cell C... Squamous Cell C... Primary Adenoca... Primary Adenoca... Renal Medullary... Squamous Cell C...	Sacituzumab gov... Atezolizumab	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Prophylactic Cranial Irradiation (PCI) for Small Cell Carcinoma of the Urothelium	NCT00756639	Bladder Cancer	Prophylactic Cr... Brain X-ray	18 Years -	M.D. Anderson Cancer Center
Prophylactic Cranial Irradiation (PCI) for Small Cell Carcinoma of the Urothelium	NCT00756639	Bladder Cancer	Prophylactic Cr... Brain X-ray	18 Years -	M.D. Anderson Cancer Center
Prophylactic Cranial Irradiation (PCI) for Small Cell Carcinoma of the Urothelium	NCT00756639	Bladder Cancer	Prophylactic Cr... Brain X-ray	18 Years -	M.D. Anderson Cancer Center
Lurbinectedin With or Without Avelumab in Small Cell Carcinoma of the Bladder (LASER)	NCT06228066	Small Cell Carc... High Grade Neur...	Lurbinectedin Avelumab	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for small cell carcinoma of the bladder