Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Urinary Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Patients will undergo MRI followed by TURBT

In our study we aim to evaluate role of Multiparametric MRI in differentiation between invasive and non-invasive bladder cancer and accuracy of vesical imaging reporting and data system (VI-RADS) score.

multi parametric MRI

detection of degree of invasion to test accuracy of ViRADS score

transurethral resection of bladder tumor

ahmed Tawfeek, ass. Professor

eslam mohamed

To evaluate the accuracy of Multiparametric MRI in differentiation between invasive and non-invasive bladder cancer using vesical imaging reporting and data system (VI-RADS) score.

Bladder cancer (BC) is one of the most common and expensive human malignancies to manage. Most BCs are urothelial cell carcinomas (UCCs), and histologically stratified into cancers with low and high grade. The latter are subdivided into those with and without muscle invasion.(1) Non-muscle-invasive BCs (NMIBCs) are often low grade and have an indolent natural history. Muscle-invasive BCs (MIBCs) are aggressive tumors with an ominous prognosis. (2) Non-muscle invasive bladder cancer is treated with transurethral resection of bladder tumor with or without adjuvant intravesical chemotherapy or photodynamic therapy, whereas muscle-invasive bladder cancer is treated with radical cystectomy, radiation therapy, chemotherapy, or a combination(3).

Bladder cancer staging is accomplished by the combination of clinical (examination), pathologic (transurethral resection of bladder tumor specimens), and radiologic means. The quality of the transurethral resection of bladder tumors often varies among surgeons, and it may miss muscle infiltration in up to 25% of invasive cancers. (4) Radiological examination looks for second urinary tract malignancies (5% of BCs may have an upper tract UCC) or other pathologies. Most guidelines suggest cross-sectional imaging for MIBCs and high-grade NMI cancers, due to the risks of invasion and regional or distant metastases, and upper urinary tract involvement. (5) MRI is currently the best imaging technique for bladder cancer local regional staging because of its superior soft tissue contrast, lack of ionizing radiation, in addition, it clearly differentiates the layer of bladder wall and enables accurate assessment of tumor depth invasion in bladder wall and extra-vesical extension. (6) During the past few years, important improvements in MRI technology have been achieved and led to the introduction of Multiparametric MRI (mp MRI) which combines functional sequences as diffusion weighted imaging (DWI) and dynamic contrast enhanced MRI (DCE-MR) with anatomic T1 and T2 weighted images (T1 and T2WI), that improves the accuracy of tumor detection and staging, helps to monitor post-therapy response and identify local disease recurrence. (7) Recently also standardized approach for imaging and reporting mp-MRI for bladder cancer was created by developing VI-RADS score (Vesical Imaging Reporting and Data System). This aims to standardize bladder mpMRI for clinical and research applications to create a systematic approach for reporting bladder mp-MRI and defining the risk of muscle invasion (NMIBC versus MIBC). (8) The Final VI-RADS score is generated using all categories and suggests the probability of muscle invasion ,It's graded from VIRADS 1 (muscle invasion is highly unlikely) to VI-RADS 5 (ivasion of muscle and beyond the bladder is very likely) (9) In our study we aim to evaluate role of Multiparametric MRI in differentiation between invasive and non-invasive bladder cancer and accuracy of vesical imaging reporting and data system (VI-RADS) score.

2- AIM:

To evaluate the accuracy of Multiparametric MRI in differentiation between invasive and non-invasive bladder cancer using vesical imaging reporting and data system (VI-RADS) score.

Validation of VI-RADS for the Detection of Detrusor Muscle Invasion

Multiparametric MRI for Bladder Cancer: Validation of VI-RADS for the Detection of Detrusor Muscle Invasion

Ain Shams University

Egyptian Biomedical Research Network

Assistant Professor of Urology

Subjects undergoing transurethral resection of bladder tumor or other transurethral biopsy procedure who agree to provide bladder tissue specimens

provision of bladder tissue via cystoscopic biopsy during planned TURBT

Bladder biopsy

Sunita Sheth, MD

The objective of the study is to obtain bladder tissue specimens from patients otherwise undergoing cystoscopy for use in research at Tengion, Inc.

Multi Center Study to Obtain Bladder Tissue Specimens From Patients Undergoing Transurethral Resection Biopsy Procedure

A Multi Center Study to Obtain Bladder Tissue Specimens From Subjects Undergoing Transurethral Resection of Bladder Tumor (TURBT) or Other Transurethral Biopsy Procedures

Tengion

Sunita Sheth, MD Chief Medical Officer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Pembrolizumab

Immunomodulating Agents

Antimetabolites

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

* Lead-in single dose Pembrolizumab 200 mg, intravenously (IV)
* Transurethral Resection of Bladder Tumor (TURBT) at pre-RT (maximal) and completion of therapy (diagnostic)
* External Beam Radiation Therapy (EBRT) - 52 Gy in 20 fractions over 4 weeks (1 fraction = 2.6 Gy)
* Gemcitabine 27 mg/m\^2 IV twice weekly for 4 weeks concurrent with EBRT
* Pembrolizumab 200 mg IV every 3 weeks for total 3 doses starting day 1 of EBRT

Transurethral Resection of Bladder Tumor

External Beam Radiation Therapy

Scot Niglio, MD

This trial is to assess the efficacy of pembrolizumab (MK3475) added to concurrent radiation and gemcitabine in the management of patients with muscle-invasive urothelial cancer who are not candidates for or decline radical cystectomy.

The investigators hypothesize that the addition of immune checkpoint inhibition with pembrolizumab, an anti-PD-1 inhibitor, to chemo-radiation therapy to the bladder may work to both increase eradication of local tumor as well as distant micrometastases through heightened immune surveillance.

Due to the lack of a previous phase I trial establishing the safety of this combination (pembrolizumab, gemcitabine, and radiation therapy (RT)), an initial safety lead-in cohort of 3 to 6 patients is enrolled for assessing dose-limiting toxicities. Similar to the Phase I 3+3 design, if there is no or only one patient in that cohort experiencing a dose-limiting toxicity, the trial continues to the Phase II part to enroll additional 48 patients for efficacy evaluation.

Pembrolizumab (MK3475), Gemcitabine, and Concurrent Hypofractionated Radiation Therapy for Muscle-Invasive Urothelial Cancer of the Bladder

A Phase II Trial of MK3475 in Combination With Gemcitabine and Concurrent Hypofractionated Radiation Therapy as Bladder Sparing Treatment for Muscle-Invasive Urothelial Cancer of the Bladder

Bladder-intact disease-free survival is defined as time from initiation of protocol therapy until the development of muscle-invasive bladder cancer recurrence, regional pelvic recurrence, distant metastases, bladder cancer-related death, or cystectomy.

The adverse events are evaluated per Common Terminology Criteria for Adverse Events (CTCAE) 4.

The CR rate is the percentage of patients who have achieved CR. At the completion of protocol therapy, patients undergo standard cystoscopy, exam under anesthesia and transurethral resection of bladder tumor to document pathologic response. CR requires no tumor palpable on bimanual examination under anesthesia, no tumor visible on cystoscopy, negative tumor site biopsy, and negative urine cytology.

Defined as time to death from beginning of protocol therapy.

Defined as time to the development of radiographic distant metastases from beginning of protocol therapy.

Merck Sharp & Dohme LLC

NYU Langone Health

Rare Diseases

Carcinoma

Carcinoma, Transitional Cell

Transitional Cell Carcinoma

Pharmaceutical Solutions

Micronutrients

Amino Acids

Glycine

Silicon

Patients randomized to HoLERBT group will have their tumor resected using the Megapulse 70w (Richard Wolf).

Patients randomized to control arm will undergo a monopolar transurethral resection of bladder tumor.

Patients randomized to Monopolar TURBT will be operated using a 26F continuous-flow resectoscope sheaths and a single-pole working element to exclusive use of the resection. The power will be set to cut in 80w and 60w. The technique that will be performed will be the classic endoscopic resection from the top of the tumor until reaching the base, taking a sample from the base of the lesion (muscle layer). Fragments will be removed through an Ellik evacuator, and the solution used will be 3% glycine. After the procedure, the patient will will be catheterized with a silicon catheter number 22F with three ways and continuous irrigation.

After 30-60 days of the first procedure, all patients diagnosed with a lamina propria invasion in the uro-pathology analysis (T1) will be submitted to a new monopolar TURBT.

Monopolar Transurethral resection of bladder tumor

It will be used a 24-26F continuous-flow resectoscope sheath with a specific working element to use with a 600µm fiber to Laser Holmium.

Patients will be operated with the Megapulse 70w (Richard Wolf) and laser will be set to deliver the energy of 0,5J and 30-40Hz frequency, 15-20W of final energy. The solution used will be 0,9% saline solution. The resection will start from the base of the lesion, reaching the muscle layer to obtain a sample and resection of the whole tumor, without fragmentation. After this, the morcellation will be performed in the apex of tumor sparing the base with a long nephroscope, and the patient will will be catheterized with a silicon catheter number 22F with three ways and continuous irrigation. The morcellated product will be sent to the pathology lab for detailed analysis.

Holmium Laser resection of bladder tumor (HoLEBT)

Alexandre Iscaife, MD, PhD

William Nahas, MD, PhD

Bladder urothelial cancer is the second most common urologic tumor and represents a worldwide public health problem. Most cases are diagnosed as non-muscle invasive tumors, and can be treated with transurethral resection of bladder tumor (TURBT). However, the electrical energy-based TURBT fragments the tumor, burning it to its own muscular layer leading to artifacts that may spoil the histopathological analysis, resulting in understaging after the first TURBT ranging from 30-64%, depending on the presence of detrusor muscle. Modern laser technologies have been emerging as an alternative to classical TURB using en bloc tumor resection technique (ERBT). Therefore, the laser is applied on tumor's pedicle to resect the whole and intact tumor without fragmentation or fulguration as occurs in TURBT. The purpose of using laser if to improve the resection quality, decrease intra and perioperative complications, avoid re-TURBT and reduce recurrence rates at the resection site and in distant sites. Thus, the purpose of this study is to evaluate Laser Holmium use for large tumors resection (\>3cm), reducing complications, costs, and the need for new approaches, and improving the muscle layers samples.

This is a single-institution, randomized, single-blinded, prospective, controlled study, with 2 groups - 50 patients in Holmium Laser En-bloc Resection of Bladder Tumors (HoLERBT) arm and 50 patients in TURBT arm. All the patients will undergo a new procedure between 30-60 days after the first one (monopolar re-TURBT). The laser group will be operated by an experienced surgeon with more than 50 cases of prostate resection. The monopolar TURBT group will be operated by institutions´s surgeons assistants, urologists with more than 2 years of experience in the area and more than 50 surgeries performed. Pathological samples will be analyzed in the FMUSP Urology Laboratory by a pathologist with huge experience in analysis of bladder tumors.

Safety Analysis and Oncological Outcomes in HoLERT vs TURBT

Safety Analysis and Oncological Outcomes in Endoscopic Bladder Tumor Resection With Laser Holmium Compared With Transurethral Resection: a Prospective and Randomized Study

Evaluate the presence of muscle layer in the samples of tumor resection

Evaluate intra and peri-operative complications (according to Clavien-Dindo scale) between the two groups

Clinical recurrence-free survival at 3, 6, 9, 12, 15, 18 and 24 months follow-up (US, CT-scan, MRI, cystoscopy, TURBT)

Clinical progression-free survival at 3, 6, 9, 12, 15, 18 and 24 months follow-up (US, CT-scan, MRI, TURBT)

Overall and cancer-specific survival at 13, 6, 9, 12, 15, 18 and 24 months follow-up

Instituto do Cancer do Estado de São Paulo

Md, PhD

Symptoms and General Pathology

Neoplastic Cells, Circulating

Adjuvants, Anesthesia

Analgesics

Central Nervous System Depressants

Central Nervous System Stimulants

Psychotropic Drugs

Platelet Aggregation Inhibitors

Other Dietary Supplements

Sufentanil

Anesthetics

Rocuronium

Caffeine

Ropivacaine

Midazolam

Propofol

Sevoflurane

Remifentanil

Desflurane

Dsuvia

Patients in this group will receive general anesthesia during TURBT.

Patients in this group will receive spinal anesthesia during TURBT.

Patients will have TURBT under general anesthesia, which is induced with midazolam, propofol, sufentanil and rocuronium. The patients will be mechanically ventilated with laryngeal mask airway (LMA). Anesthesia will be maintained with sevoflurane/desflurane, propofol and remifentanil.

General Anesthesia

Patients will have TURBT under spinal anesthesia. 10\~15mg of 0.5% ropivacaine will be injected in the subarachnoid cerebrospinal fluid at the levels of L2-L3 or L3-L4 in lumbar space. It will numb the nerve supply of the belly, hips, bottom as well as legs. The patient stays awake and won't feel any pain due to operation.

Spinal Anesthesia

Multiple lines of evidence have shown that anesthesia method is associated with long-term outcomes in patients undergoing surgery due to cancers, including lung, breast, prostate, and bladder cancer, etc. Circulating tumor cells (CTCs) have been validated as prognostic biomarkers of a number of cancers. The aim of this study is to investigate the effects of anesthesia methods on the number of CTCs in patients receiving transurethral resection of bladder tumor (TURBT). The difference of anesthesia method is achieved by using general anesthesia in one group and spinal anesthesia in the other group.

Influence of Anesthesia Methods on CTCs in TURBT Patients

Influence of General Anesthesia Versus Spinal Anesthesia on Circulating Tumor Cells in Patients Undergoing Transurethral Resection of Bladder Tumor

The number of circulating tumor cells will be measured by collecting 5 ml of venous blood sample.

The surgeon satisfaction will be measured with the Likert scale, which ranges from 0 to 50, with a higher score indicating higher satisfaction.

The patient satisfaction will be measured with the Modified Bauer Scale, which ranges from 0 to 50, with a higher score indicating higher satisfaction.

Pain intensity will be assessed using the Visual Analogue Scale, which ranges from 0 to 10, with a higher score indicating greater pain intensity at 24 hours after surgery.

Nausea score will be assessed using the Numerical Rating Scale, which ranges from 0 to 10, with a higher score indicating greater nausea ou score at 24 hours after surgery.

The length of hospital stay will be recorded.

RenJi Hospital

Principal Investigator

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Anti-Infective Agents

Fluorouracil

Cisplatin

Atezolizumab

Mitomycins

Mitomycin

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Alkylating Agents

Enzyme Inhibitors

Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks. Patients also receive chemotherapy based on physician's choice of gemcitabine IV twice weekly for 6 weeks concurrent with RT, or cisplatin IV weekly for 6 weeks concurrent with RT, or fluorouracil IV on same days as doses 1-5 and 16-20 of radiation therapy and mitomycin IV on day 1 of radiation therapy in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5.

Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks and receive chemotherapy based on physician's choice as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5.

Biopsy of Bladder

Computed Tomography

Cystoscopy

Magnetic Resonance Imaging

Quality-of-Life Assessment

Radiation Therapy

Survey Administration

Parminder Singh

This phase III trial studies how well chemotherapy and radiation therapy work with or without atezolizumab in treating patients with localized muscle invasive bladder cancer. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Chemotherapy drugs, such as gemcitabine, cisplatin, fluorouracil and mitomycin-C, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with radiation therapy may kill more tumor cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving atezolizumab with radiation therapy and chemotherapy may work better in treating patients with localized muscle invasive bladder cancer compared to radiation therapy and chemotherapy without atezolizumab.

PRIMARY OBJECTIVE:

I. To compare bladder intact event-free survival (BI-EFS) for concurrent chemoradiation therapy (CRT) with and without atezolizumab in localized muscle invasive bladder cancer (MIBC).

SECONDARY OBJECTIVES:

I. To compare overall survival between the two arms. II. To compare modified bladder intact event-free survival including cancer related death between arms.

III. To compare complete and partial pathologic response between arms at 3 months after completing chemoradiation therapy.

IV. To estimate metastases-free survival by arm. V. To compare the qualitative and quantitative adverse events from each arm. VI. To estimate the rate of non-muscle invasive bladder cancer recurrence by arm.

VII. To estimate the rate of salvage cystectomy and reasons for cystectomy by arm.

VIII. To compare mean patient-reported global quality of life (QOL) at week 54 using the European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire (QLQ)-Core (C)30 Global Health Status (GHS) subscale score between patients with localized muscle-invasive bladder cancer randomized to chemoradiation with versus (vs.) without atezolizumab.

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To test the hypothesis that a panel of validated biomarkers of concurrent CRT involving nuclear MRE11, impaired deoxyribonucleic acid damage response (DDR) function and tumor subtyping will be prognostic for BI-EFS among patients receiving either concurrent CRT or chemoimmuno-radiotherapy (CIRT) of the primary tumor.

II. To test the hypothesis that tumor total mutation burden, neoantigen burden, infiltrating immune response, PD-L1 expression and T cell response are associated with augmented response after concurrent CIRT.

III. To bank urine specimens for future use.

PATIENT-REPORTED OUTCOMES (PROs) OBJECTIVES:

I. To compare mean patient-reported global QOL as measured by the EORTC QLQ-C30 Global Health Status subscale scores at week 54 between patients with localized muscle-invasive bladder cancer randomized to chemoradiation with vs. without atezolizumab. (Primary) II. To compare mean patient-reported bowel symptoms at each assessment time by arm using the Expanded Prostate Cancer Index Composite (EPIC) Bowel Assessment from the Expanded Prostate Index, the bladder-specific supplement to the QLQ-C30, the EORTC QLQ-Muscle Invasive Bladder Cancer (BLM30), the Physical Functioning subscale of the EORTC QLQ-C30, and overall health status using the EuroQol Five Dimension Five Level Scale (EQ-5D-5L). (Exploratory) III. To compare longitudinal change over time by arm in patient-reported global QOL using the EORTC QLQ-C30, the Bowel Domain of the Expanded Prostate Index (EPIC Bowel Assessment), the bladder-specific supplement to the QLQ-C30, the EORTC QLQ-BLM30, the Physical Functioning subscale of the EORTC QLQ-C30, and overall health status using the EQ-5D-5L. (Exploratory)

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo radiation therapy (RT) (3 dimensional \[D\] CRT or intensity-modulated radiation therapy \[IMRT\]) daily Monday-Friday for up to 7-8 weeks. Patients also receive chemotherapy based on physician's choice of gemcitabine intravenously (IV) twice weekly for 6 weeks concurrent with RT, or cisplatin IV weekly for 6 weeks concurrent with RT, or fluorouracil IV on same days as doses 1-5 and 16-20 of radiation therapy and mitomycin IV on day 1 of radiation therapy in the absence of disease progression or unacceptable toxicity. Patients also undergo a transurethral resection of bladder tumor (TURBT) with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6 months through year 5 and computed tomography (CT) or magnetic resonance imaging (MRI) at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5.

ARM II: Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks and receive chemotherapy based on physician's choice as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6 months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5.

After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years.

Chemoradiotherapy With or Without Atezolizumab in Treating Patients With Localized Muscle Invasive Bladder Cancer

Phase III Randomized Trial of Concurrent Chemoradiotherapy With or Without Atezolizumab in Localized Muscle Invasive Bladder Cancer

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

A Cox regression model will be used to evaluate the main effects of treatment arm and the main effect for each stratification factor and the interaction of the stratification factor with treatment in terms of both the primary endpoint and secondary endpoints. The stratification factors to be evaluated include: (1) clinical stage T2 vs. T3/T4a, (2) intended chemotherapy regimen cisplatin vs. 5-FU + mitomycin-C vs. gemcitabine, (3) radiation field small pelvis vs. bladder only and (4) performance status 0-1 vs. 2. There may be other radiation summary measures that may also be explored in terms of their modification of the experimental treatment effect including extent of radiation to lymph node fields. Subgroup analysis defined by stratification factors will also be conducted for primary endpoint and key secondary.

At each time point, futility will be evaluated, and in the latter two analyses, efficacy will also be evaluated as specified. The final BI-EFS intent-to-treat analysis will be conducted using a stratified logrank test stratifying on stratification factors, and testing treatment at the one-sided significance level of 0.022 to account for multiple interim testing. The hazard ratio (HR) will be estimated using a stratified Cox proportional hazards model and the 95% confidence interval (CI) for the HR will be provided. Results from an unstratified analysis will also be provided. Kaplan-Meier methodology will be used to estimate the median BI-EFS for each treatment arm.

Will be estimated using Kaplan-Meier methodology for each treatment arm. Will be analyzed using a similar method as for BI-EFS.

Analysis of modified BI-EFS, i.e., a sensitivity analysis of BI-EFS, where bladder cancer event is defined as histologically proven presence of muscle invasive bladder cancer, clinical evidence of nodal or metastatic disease, radical cystectomy, or death within 90 days of receiving protocol specified treatment, will also be conducted.

The Cochran-Mantel-Haenszel statistic will be used with modified ridit scores to evaluate the biopsy outcomes of complete response versus (vs.) down-staging vs. no response for the two treatment arms.

For the subset of patients who achieve a complete response during the week 18 biopsy window, complete response duration is defined from the date of the biopsy documenting the complete response to the time of muscle invasive recurrence, local progression, evidence of metastatic disease or death due to any cause. Will be analyzed using a similar method as for BI-EFS.

Assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ)-C30. Will be examined using linear mixed models with patient considered as the random effect. The baseline physical function score and the stratification factors will be included in the regression model as adjustment covariates.

National Cancer Institute (NCI)

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Hematinics

Vitamins

Doxorubicin

Liposomal doxorubicin

Methotrexate

Vinblastine

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Tubulin Modulators

Antimitotic Agents

Folinic Acid

Folate

Vitamin B9

Trimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then chemoradiation followed by TURBT#3

Trimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then active surveillance

Trimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then intravesicle therapy followed by TURBT#3

Trimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then cystectomy

Administered Day 1 of each 14 day cycle for 3 cycles

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 from Monday to Friday

Intensity modulated radiation therapy (IMRT)

Performed at before and after AMVAC and after chemoradiation and intravesicle therapy

Transurethral Resection of Bladder tumor

Continuous 24hr Intravenous infusion days 1-5 and 16-20 with radiation treatment

5-FU

Intravenous on day 1 with radiation treatment

Mitomycin C

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 accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) 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 therapy, chemoradiation 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.

This phase II trial studies how well maximal transurethral surgery (surgery performed with a special instrument inserted through the urethra) followed by accelerated methotrexate, vinblastine, doxorubicin hydrochloride, cisplatin, and radiation therapy work in treating patients with bladder cancer that has spread to the muscle. Drugs used in chemotherapy, such as methotrexate, vinblastine sulfate, doxorubicin hydrochloride, and cisplatin 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. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving chemotherapy with radiation therapy may kill more tumor cells. Giving combination chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Risk Enabled Therapy After Initiating Neoadjuvant Chemotherapy for Bladder Cancer (RETAIN)

A Phase II Trial of Risk Enabled Therapy After Initiating Neoadjuvant Chemotherapy for Bladder Cancer (RETAIN BLADDER)

At each cystoscopic examination, the location and extent of tumor volume will be visually depicted and graded according to Endoscopic Tumor Quantification System

American Urologic Association (AUA) Symptom Index Score, Sexual Health Inventory for Men (SHIM) score or Female Sexual Function Index (FSFI) score

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Validation of VI-RADS for the Detection of Detrusor Muscle Invasion	NCT05123404	Bladder Cancer	multi parametri... transurethral r...	-	Egyptian Biomedical Research Network
Validation of VI-RADS for the Detection of Detrusor Muscle Invasion	NCT05123404	Bladder Cancer	multi parametri... transurethral r...	-	Egyptian Biomedical Research Network
Multi Center Study to Obtain Bladder Tissue Specimens From Patients Undergoing Transurethral Resection Biopsy Procedure	NCT00615043	Bladder Disease	Bladder biopsy	18 Years - 90 Years	Tengion
Pembrolizumab (MK3475), Gemcitabine, and Concurrent Hypofractionated Radiation Therapy for Muscle-Invasive Urothelial Cancer of the Bladder	NCT02621151	Muscle-invasive...	Pembrolizumab Transurethral R... Gemcitabine External Beam R...	18 Years -	NYU Langone Health
Safety Analysis and Oncological Outcomes in HoLERT vs TURBT	NCT05833997	Bladder Urothel... Bladder Cancer	Monopolar Trans... Holmium Laser r...	18 Years - 80 Years	Instituto do Cancer do Estado de São Paulo
Influence of Anesthesia Methods on CTCs in TURBT Patients	NCT05824299	Bladder Cancer	General Anesthe... Spinal Anesthes...	18 Years - 85 Years	RenJi Hospital
Chemoradiotherapy With or Without Atezolizumab in Treating Patients With Localized Muscle Invasive Bladder Cancer	NCT03775265	Bladder Urothel... Muscle Invasive... Stage II Bladde... Stage IIIA Blad...	Atezolizumab Biopsy of Bladd... Cisplatin Computed Tomogr... Cystoscopy Fluorouracil Gemcitabine Magnetic Resona... Mitomycin Quality-of-Life... Radiation Thera... Survey Administ... Transurethral R...	18 Years -	National Cancer Institute (NCI)
Multi Center Study to Obtain Bladder Tissue Specimens From Patients Undergoing Transurethral Resection Biopsy Procedure	NCT00615043	Bladder Disease	Bladder biopsy	18 Years - 90 Years	Tengion
Risk Enabled Therapy After Initiating Neoadjuvant Chemotherapy for Bladder Cancer (RETAIN)	NCT02710734	Urothelial Carc...	Methotrexate Vinblastine Doxorubicin Cisplatin Intensity modul... Transurethral R... 5-FU Mitomycin C	18 Years -	Fox Chase Cancer Center
Study to Determine Possible Effects of Apalutamide on EGFR Expression in Patients With Non-muscle Invasive Bladder Cancer	NCT05521698	Non-Muscle Inva... Recurrent Non-M...	Apalutamide Biospecimen Col... Questionnaire A... Transurethral R...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for transurethral resection of bladder tumor