Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Urinary Bladder Neoplasms

Disease Progression

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

Consolidative radiotherapy (pelvic irradiation and/or metastases irradiation) + standard of care +/- previous transurethral resection of bladder tumor

Experimental arm

Jonathan KHALIFA

Laurent VOTRON

Nathalie MESGOUEZ-NEBOUT

Jihane BOUSTANI

Paul SARGOS

Ulrike SCHICK

Matthieu CHASSERAY

Pierre-Emmanuel BRACHET

Thomas MULLIEZ

David PASQUIER

Naji SALEM

Médéric BARRET

Gilles CREHANGE

Valentine GUIMAS

Hugo PICCHI

Nicolas MAGNE

Pierre BLANCHARD

This is a phase II, multicenter, randomized open-label and comparative study designed to evaluate whether local consolidative radiotherapy plus standard of care improves overall survival as compared to standard of care in patients with limited metastatic urothelial bladder cancer and without progression following the initial phase of first-line systemic therapy.

Each patient will be followed during 4 years from the date of randomization.

Consolidative Radiotherapy for Metastatic Urothelial Bladder Cancer Patients Without Progression and With no More Than Three Residual Metastatic Lesions Following First Line Systemic Therapy

Consolidative Radiotherapy for Metastatic Urothelial Bladder Cancer Patients Without Progression and With no More Than Three Residual Metastatic Lesions Following First Line Systemic Therapy: a Prospective Randomized Comparative Phase II Trial

Institut Claudius Regaud

mpMRI in addition to the TURBT surgical procedure

mpMRI + Diagnostic TURBT

Chao Family Comprehensive Cancer Center University of California, Irvine

University of California Irvine Medical

Nataliya Mar, MD

This is a pilot, single arm, prospective study that aims to validate the accuracy of the VI-RADS score obtained via multi-parametric magnetic resonance imaging (mpMRI) compared to pathologic cancer stage obtained via diagnostic transurethral bladder tumor resection (TURBT) as well as compare the clinical and quality of life outcomes between these diagnostic modalities in patients with suspected muscle-invasive bladder cancer (MIBC).

mpMRI Compared to Diagnostic TURBT in Patients With Suspected Muscle-Invasive Bladder Cancer

Outcomes With Multi Parametric MRI (mpMRI) Compared to Diagnostic Transurethral Resection of Bladder Tumor (TURBT) in Patients With Suspected Muscle-Invasive Bladder Cancer - a Pilot Study

VI-RADS is a five-point scoring system developed to standardize imaging and reporting of bladder tumor invasiveness on mpMRI. It predicts the degree of possible muscular propria invasion ("muscle-invasiveness") of bladder tumors. Once diagnostic TURBT is performed, the VI-RADS score from mpMRI will be compared to the pathologic tumor (T) stage from a diagnostic TURBT to assess for concordance.

Time from diagnostic test to cancer progression, recurrence, or death.

As assessed by quality of life questionnaires

University of California, Irvine

Associate Professor

Rare Diseases

Carcinoma

Carcinoma, Transitional Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

All Drugs and Chemicals

Antineoplastic Agents

Mitogens

Infigratinib

Participants will be randomly assigned (1:1) to receive oral infigratinib administered once daily for the first 3 weeks (21 days) of each 28-day cycle for a maximum of 52 weeks

Participants will be randomly assigned (1:1) to receive oral placebo administered once daily for the first 3 weeks (21 days) of each 28-day cycle for a maximum of 52 weeks

Participants randomly assigned to infigratinib will receive hard gelatin capsules for oral administration of infigratinib 125 mg once a day (administered as one 100-mg capsule and one 25-mg capsule) using a 3 weeks on (Days 1-21) /1 week off (Days 22-28) dosing schedule.

Participants randomly assigned to placebo will receive placebo matching in appearance the investigational product (infigratinib), which will be provided as hard gelatin capsules for oral use and will be administered once daily on a 3 weeks on (Days 1-21) /1 week off (Days 22-28) dosing schedule.

Placebo

David van Veenhuyzen, M.B., Ch.B., M.Pharm.Med.

This is a Phase 3 multicenter, double-blind, randomized, placebo-controlled study to evaluate the efficacy of infigratinib (an oral targeted FGFR1-3 inhibitor) versus placebo, as adjuvant treatment following surgery in adult subjects with invasive urothelial carcinoma and susceptible FGFR3 genetic alterations (mutations, and gene fusions or rearrangements) who have disease that is considered at high risk for recurrence with surgery alone. The study enrolls subjects with either bladder cancer post radical cystectomy or upper tract urothelial cancer post distal ureterectomy and/or nephrectomy. Study treatment is randomized 1:1 between infigratinib or placebo with treatment up to 1 year or until invasive local, distal, or metastatic disease recurrence confirmed by independent imaging reviewer.

Participants will be randomly assigned (1:1) to receive oral infigratinib phosphate or placebo

As a double-blind study, participants, investigators, study monitor(s) and the clinical study team will be blinded to the treatment administered.

Oral Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations

Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations (PROOF 302)

DFS was defined as the number of months from date of randomization to local/regional invasive or metastatic recurrence or death due to any cause (referred as DFS event), whichever occurs earlier.

Due to early termination of the study by the sponsor, results will focus primarily on the primary and key secondary endpoints of the study. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.

DFS was defined as the number of months from date of randomization to local/regional invasive or metastatic recurrence or death due to any cause (referred as DFS event), whichever occurs earlier. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.

MFS was defined as the time from randomization to any metastatic recurrence as determined by the investigator, or death due to any cause, whichever occurred earlier. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.

Overall survival time was defined as the number of months from randomization to death. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.

Investigator assessment of intraluminal low-risk recurrence as assessed by DFS. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.

Helsinn Healthcare SA

QED Therapeutics, Inc.

AEs were assessed by the investigator according to the CTCAE version 5.0 and coded using MedDRA version 23.1.

Treatment-emergent AEs are reported and include all AEs with onset after the first administration of study treatment and up to last administration of study treatment + 30 days if subjects ended study treatment. For a subject who had not ended study treatment, all the AEs after the first administration of study drug were considered treatment-emergent.

Infigratinib 125 mg once daily (3 weeks on / 1 week off treatment)

Infigratinib 125 mg

Placebo once daily (3 weeks on / 1 week off treatment)

125 mg oral infigratinib once daily for the first 3 weeks (21 days) of each 28-day cycle

Placebo once daily for the first 3 weeks (21 days) of a 28-day treatment cycle

Total

Age Group

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

North America

Europe

North America includes United States and Canada; Europe includes Germany, Spain, France, Italy, Netherlands, and Belgium

Region of Enrollment

Functional status was assessed at baseline using the Eastern Cooperative Oncology Group Performance Scale (ECOG PS), defined as follows:

0. Fully active, able to carry out all pre-disease performance without restriction.

1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature.
2. Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours.
3. Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours.
4. Completely disabled.

ECOG PS

Primary Site of Cancer

Histological Subtype

Tumor (T). T1, T2, T3, T4: Refers to the size and/or extent of the main tumor. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues.

Screening Diagnosis Category (Pathologic Stage at Definitive Surgery) - Tumor (T)

Node (N) refers to the number of nearby lymph nodes that have cancer. NX: Cancer in nearby lymph nodes cannot be measured; N0: There is no cancer in nearby lymph nodes; N1, N2, N3: Refers to the number and location of lymph nodes that contain cancer. The higher the number after the N, the more lymph nodes that contain cancer.

Screening Diagnosis Category (Pathologic Stage at Definitive Surgery) - Node (N)

Time from Initial Diagnosis to Randomization (Days)

Type of FGFR3 Alteration (Local)

FGFR3 Mutation Result (Local)

FGFR3 Fusion Result (Local)

Type FGFR3 Alteration (Central)

FGFR3 Mutation Result (Central)

FGFR3 Fusion Result (Central)

Tumor Mutational Burden

Acting Chief Medical Officer

Intent-to-treat (ITT) population, which included all subjects who were randomized

Centrally Determined Disease-free Survival (DFS)

ITT population includes all subjects who were randomized

Investigator-assessed DFS

Metastasis-free Survival (MFS)

Overall Survival (OS)

Investigator-reviewed DFS Including Intraluminal Low-Risk Recurrence

Number of Participants With Adverse Events (AEs)

Number of Participants With Serious Adverse Events (SAEs)

Participants were randomly assigned (1:1) to receive oral infigratinib administered once daily for the first 3 weeks (21 days) of each 28-day cycle for a maximum of 52 weeks.

Infigratinib: Participants randomly assigned to infigratinib received hard gelatin capsules for oral administration of infigratinib 125 mg once a day (administered as one 100-mg capsule and one 25-mg capsule) using a 3 weeks on (Days 1-21) /1 week off (Days 22-28) dosing schedule.

Participants were randomly assigned (1:1) to receive oral placebo administered once daily for the first 3 weeks (21 days) of each 28-day cycle for a maximum of 52 weeks.

Placebo: Participants randomly assigned to placebo received placebo matching in appearance the investigational product (infigratinib) provided as hard gelatin capsules for oral use and administered once daily on a 3 weeks on (Days 1-21) /1 week off (Days 22-28) dosing schedule.

Overall Study

Immune System Diseases

Digestive System Diseases

Adenocarcinoma

Head and Neck Neoplasms

Carcinoma, Renal Cell

Hypersensitivity

Biliary Tract Neoplasms

Kidney Neoplasms

Kidney Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Renal Cell Carcinoma

Biliary Tract Cancer

Clear Cell Renal Cell Carcinoma

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Antibodies

Antibodies, Monoclonal

Niraparib

Dostarlimab

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Adenosine

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Substance: immunoglobulin G4 (IgG4) humanized monoclonal antibody (mAb) that binds with high affinity to PD-1 Manufacturer: Tesaro Inc. Dose: 500 mg every 21 days for the first 4 cycles, followed by 1,000 mg every 42 days cycle (ie, Q6W)

Substance: Inhibitor of poly-adenosine diphosphate \[ADP\] ribose polymerase (PARP) Manufacturer: Tesaro Inc. Dose: Flat-fixed dose (if \<77kg or platelets \<150,000 μL: 200mg; if \>/=77kg and platelets \>/= 150,000μL: 300mg)

Treatment will consist of a PARP inhibitor (niraparib) monotherapy priming period (cycle 0; 21 days); an anti-PD-1 antibody (Dostarlimab ; TSR-042) will then be added from C1D1 every 21 days in combination for the first 4 cycles, and then every 42 days. Disease will be assessed every 2 cycles (6 weeks) from C3D1 by CT-scan (or MRI or bone scan, if relevant). Patients still under treatment after 1 year may have tumor evaluation spaced out every 3 cycles

This study will make it possible to evaluate the efficacy and safety of use of the combination of two products: niraparib and Dostarlimab (also called TSR-042). It will assess whether these two drugs can not only stop the growth of tumor cells but also activate immune cells to kill them.

Patients that tolerates these products well will also be monitored

The investigating doctor suggests that patient take part in this study because his disease may benefit from the treatments administered in this study. Only patients whose tumor is likely to respond to the drugs administered, based on preclinical results or clinical data, will be able to participate in this study. Patient are selected because his tumor seems to have the characteristics that allow him to be included in one of the following three cohorts:

Cohort 1: tumor has a particular mutation; this cohort will include 5 groups according to the type of cancer: bladder cancer (group 1A), cancer of the stomach or of the esophago-gastric junction (group 1B), head and neck cancer (group 1C), bile duct cancer (group 1D) or other cancers (group 1E) Cohort 2: tumor is bladder cancer and has shrunk under previous treatment with platinum salts Cohort 3: clear cell kidney cancer. These products have already been tested in combination and their combination has shown that it is possible without causing toxicity.

About 120 patients will participate in the study in several centers in France. All patients will receive the combination of these two treatments.

Basket Trial Exploring the Efficacy and Safety of the Combination of Niraparib and Dostarlimab

An Open Label Phase II Basket Trial Exploring the Efficacy and Safety of the Combination of Niraparib and Dostarlimab in Patients With DNA Repair-deficient or Platinum-sensitive Solid Tumors

according to Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1)

Gustave Roussy, Cancer Campus, Grand Paris

Recurrence

Subjects previously diagnosed with UC and are undergoing a schedule of surveillance cystoscopies and treatment for the possible recurrence of UC will be recruited. Only intermediate and high-risk group, according to AUA /SUO risk categorisation for non-muscle invasive UC, will be eligible for this study. All subjects will undergo CxBladder urine diagnostic testing.

CxBladder Monitor (CxbM) is a high sensitivity and negative predictive value (NPV) urinary biomarker test to rule-out subjects at low risk of bladder cancer monitoring for recurrence of disease.

CxBladder Monitor

Alexis White, BSc (Hons)

Anke Fronius

Jason Laubach

Florian Schroeck, MD

Blair Stewart

Jonathan Wright, MD

Tony Lough

Surveillance for recurrence of urothelial carcinoma (UC) requires frequent cystoscopy, which is invasive, expensive and time-consuming. An accurate urinary biomarker has the potential to reduce the number of cystoscopies required during post-treatment surveillance. This is a prospective single arm multi-center study using the diagnostic CxBladder test with subjects previously diagnosed positive with primary or recurrent UC and who are undergoing a schedule of investigative cystoscopies and treatment for the possible recurrence of urothelial carcinoma presenting to qualified sites. To test the pathway multiple consecutive urine samples will be collected during the course of surveillance and records review follow-up will also be completed.

This is a multi-site study recruiting subjects from Veterans Affairs and other medical centers. Subjects will be prospectively recruited to an observational study to validate the performance characteristics and clinical utility of CxBladder Monitor test (CxbM). The study will recruit intermediate and high-risk surveillance subjects, defined as per American Urological Association (AUA) / Society of Urologic Oncology (SUO) guidelines 2016 amendment 2020, previously diagnosed with urothelial carcinoma (UC).Eligible subjects will include those under surveillance for recurrence of UC. A strength of the proposed design is that subjects with primary or recurrence of UC can be recruited. This means, for some subjects, that there may be a range of surveillance visits prior to enrolment. A voided urine sample will be collected from each enrolled subject at each of 4 successive surveillance visits. Records review will occur 12, 24 and 48 months after the final urine sample is collected. The collected urine will be used for CxBladder testing and central urine cytology. The study will collect primary tumour tissue from the first (primary) tumour and also from the most recent recurrence, if any, in order to genotype each tumour using RNA or DNA markers indicative of an elevated risk of UC. CxBladder results will not be reported to patients or physicians. The objective of this study is to evaluate a new proposed pathway over a period of up to four visits where CxbM is alternated with cystoscopy at consecutive visits for intermediate and high-risk surveillance subjects. The new proposed pathway will be compared directly to standard of care. Analysis of data will include determining the proportion of subjects that are positive by surveillance cystoscopy (standard of care) following a negative diagnosis at the previous visit. Using the same dataset, analysis of data will include determining the proportion of subjects that are positive by surveillance cystoscopy (standard of care) following a negative CxBladder result at the previous visit. Analysis will include assessment of the theoretical possible reduction in cystoscopy procedure use associated with the new pathway. Sites are required to be competent in recruiting and completing required test request forms, Case Report Forms (CRF) and sample collection in a professional manner in accordance with good clinical practice (GCP).

CxBladder Surveillance of Intermediate and High-Risk Bladder Cancer Patients

An Observational Study of CxBladder Monitoring for Recurrence of Urothelial Carcinoma in Intermediate and High-Risk Patients

The failure rate will be measured as the proportion of all subjects experiencing a failure event. A failure event for the proposed pathway is defined as any visit where standard of care cystoscopy is confirmed as positive for a given visit when Cxbladder Monitor was negative at the immediate previous visit. A failure event for the standard of care is defined as any visit where standard of care cystoscopy is confirmed as positive for a given visit when standard of care cystoscopy was negative at the immediate previous visit. (The gold standard for determination of a confirmed clinical diagnosis is cystoscopy and any other procedures relating to the visit with confirmation by pathology following review of a biopsy specimen).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Consolidative Radiotherapy for Metastatic Urothelial Bladder Cancer Patients Without Progression and With no More Than Three Residual Metastatic Lesions Following First Line Systemic Therapy	NCT04428554	Urothelial Blad...	Experimental ar...	18 Years -	Institut Claudius Regaud
mpMRI Compared to Diagnostic TURBT in Patients With Suspected Muscle-Invasive Bladder Cancer	NCT06335667	Urothelial Blad... Muscle-Invasive...	mpMRI + Diagnos...	18 Years -	University of California, Irvine
mpMRI Compared to Diagnostic TURBT in Patients With Suspected Muscle-Invasive Bladder Cancer	NCT06335667	Urothelial Blad... Muscle-Invasive...	mpMRI + Diagnos...	18 Years -	University of California, Irvine
Oral Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations	NCT04197986	Upper Tract Uro... Urothelial Blad...	Infigratinib Placebo	18 Years -	QED Therapeutics, Inc.
Basket Trial Exploring the Efficacy and Safety of the Combination of Niraparib and Dostarlimab	NCT04779151	Urothelial Blad... Gastric Adenoca... Gastro-oesophag... Head and Neck C... Biliary Tract C... Platinum-sensit... Clear Cell Rena... Pancreatic Duct...	Dostarlimab Niraparib	18 Years -	Gustave Roussy, Cancer Campus, Grand Paris
CxBladder Surveillance of Intermediate and High-Risk Bladder Cancer Patients	NCT05080998	Urothelial Blad...	CxBladder Monit...	18 Years -	Pacific Edge Limited
Oral Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations	NCT04197986	Upper Tract Uro... Urothelial Blad...	Infigratinib Placebo	18 Years -	QED Therapeutics, Inc.
Consolidative Radiotherapy for Metastatic Urothelial Bladder Cancer Patients Without Progression and With no More Than Three Residual Metastatic Lesions Following First Line Systemic Therapy	NCT04428554	Urothelial Blad...	Experimental ar...	18 Years -	Institut Claudius Regaud

Spots Global Cancer Trial Database for urothelial bladder cancer