Neoplasms

All Conditions

Rare Diseases

Carcinoma

Carcinoma, Transitional Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

Transitional Cell Cancer of the Renal Pelvis and Ureter

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Mitomycins

Mitomycin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Alkylating Agents

Enzyme Inhibitors

The Mitomycin C (MMC) concentration of UGN-101 to be used in this trial will be 4 mg MMC per 1 mL of TC-3 gel, maximum dose is 15ml. 6 once weekly intravesical instillations for the ablation treatment.

Treatment with UGN-101 once weekly for a total of 6 times; in a retrograde fashion. Patients who will demonstrate complete response (CR) will be treated with UGN-101 once monthly as a maintenance therapy for a total of 11 instillations or up to the first recurrence whichever comes first.

UGN-101 instillations

Seth Lerner, M.D.

The study is investigating the ability of UroGen's UGN-101 to treat urothelial carcinoma tumors from the upper urinary tract.

Trial TC-UT-03 is a prospective, open label, single-arm trial, designed to assess the efficacy, safety, and tolerability of treatment with UGN-101 instilled in the upper urinary system of patients with non-invasive low-grade (LG), Upper Tract Urothelial Carcinoma (UTUC).

Upon signing of informed consent, the patients will undergo a screening visit for eligibility evaluation. Eligible patients will be treated with UGN-101 once weekly for a total of 6 times; in a retrograde fashion. Patients who will demonstrate complete response (CR) will be treated with UGN-101 once monthly as a maintenance therapy for a total of 11 instillations or up to the first recurrence whichever comes first.

Five (5) weeks (± 1 w) following the last instillation, the Primary Disease Evaluation (PDE) Visit, during which safety and efficacy will be assessed, will take place. During this visit, the ablative effect of the UGN-101 will be assessed visually, by upper tract washed urine cytology, and if there are remaining tumors, by biopsy or brush biopsy if technically feasible.

Patient demonstrating CR at PDE will undergo monthly maintenance instillations of UGN-101 up to 11 months post PDE. Safety follow-up for these patients will be done until one month post last instillation or at the end of the follow-up period in FU visit 12, which is the earlier.

For patients who did not demonstrate Complete Response, to the extent that it is possible, all remaining tumors lesions will be biopsied. The patients shall undergo any additional surgical or other treatment the Principal Investigator (PI) decides deem necessary to remove remaining tumor.

An independent Data Monitoring Committee (DMC) was assigned to this trial. Accumulating safety, tolerability and efficacy data will be monitored periodically by the DMC according to a pre-specified process and frequency detailed in the DMC charter.

The OLYMPUS Study - Optimized DeLivery of Mitomycin for Primary UTUC Study

A Phase 3 Multicenter Trial Evaluating the Efficacy and Safety of UGN-101 on Ablation of Upper Urinary Tract Urothelial Carcinoma

Treatment-emergent AEs were most frequently reported from the Renal and urinary disorders system organ class (SOC), 59 (83.1%) patients, as expected, given the underlying indication of low grade (LG) Upper tract urothelial carcinoma (UTUC) in the study population, chemotherapeutic drug in a gel matrix instilled in the upper urinary tract (UUT), and the study procedure of treatment instillation via a ureteral catheter. The toxicity within the upper urinary tract was considered consistent with the disease under study and the mode of administration of UGN-101. Most events in the Renal and urinary disorders SOC were mild to moderate in severity and resolved. No new risks were identified and the overall safety profile was consistent with the known safety profile of endoscopic administration of intravesical mitomycin and of mitomycin. Overall, based on the safety and efficacy results to date, the benefit-risk profile of UGN-101 is favorable for the treatment of LG-UTUC.

The primary efficacy endpoint was the number of patients attaining complete response (CR) at the end of the treatment period (Primary Disease Evaluation (PDE) visit). The CR was defined dichotomously as "Success" if CR was confirmed at PDE visit (or relevant follow-up), and "Failure" otherwise.

Continuously: Duration of CR or time-to-recurrence since the Primary Disease Evaluation (PDE) Visit (i.e., time in days from the visit at which CR was determined until recurrence or censoring). This endpoint served as the main long-term durability endpoint. Dichotomously: "Success" if CR was still present at the 12 month post-PDE Visit (at Follow-Up Visit 4), and "Failure" otherwise. This endpoint served as a supportive long-term durability endpoint.

Durability of CR defined dichotomously as "Success" if CR was achieved at Primary Disease Evaluation (PDE) visit and remained at follow-up Visit 1, Visit 2 and Visit 3 (3, 6, 9 and 12 months post PDE visit), and "Failure" otherwise.

Clinical benefit for patients with partial response (PR) at the PDE visit. Clinical benefit endpoint was analyzed using the Intent-to-Treat (ITT) Analysis Set, including patients who achieved partial response at PDE Visit.Partial response at PDE visit will be defined dichotomously, similarly to the primary efficacy endpoint. For subjects with partial response at PDE visit, originally planned and actual treatments will be compared.

Cmax: maximum plasma concentration

Analysis of individual plasma concentration versus time profiles showed that at 6 hours post instillation, the plasma concentrations of all 6 patients were below 2 ng/mL, with the plasma concentration of one patient dropping below the LOQ (i.e., \< 0.100 ng/mL). The mean Cmax was 6.24 ng/mL (range: 2.43 to 12.80 ng/mL). The highest individual observed Cmax value of 12.80 ng/mL was 187-fold and 40 fold lower than the observed Cmax level following an intravenous bolus dose of 30 mg or 10 mg mitomycin (2.4 μg/mL and 0.52 μg/mL, respectively) and is 31 fold lower than the threshold value of 400 ng/mL for myelosuppression observed with mitomycin.

Tmax: time to maximum plasma concentration

Analysis of individual plasma concentration versus time profiles showed that at 6 hours post instillation, the plasma concentrations of all 6 patients were below 2 ng/mL, with the plasma concentration of one patient dropping below the LOQ (i.e., \< 0.100 ng/mL).

The mean Cmax was 6.24 ng/mL (range: 2.43 to 12.80 ng/mL), and the Tmax was 1.79 hours (range: 0.50 to 5.17 hours) after instillation. The highest individual observed Cmax value of 12.80 ng/mL was 187-fold and 40 fold lower than the observed Cmax level following an intravenous bolus dose of 30 mg or 10 mg mitomycin (2.4 μg/mL and 0.52 μg/mL, respectively) and is 31 fold lower than the threshold value of 400 ng/mL for myelosuppression observed with mitomycin.

Half-life (t½): terminal half-life

The mean apparent t½ following instillation of mitomycin into the upper urinary tract (UUT) was 1.27 hours (76 minutes), which was longer than the true t½ of mitomycin following a 30 mg bolus injection (mean t½ value of approximately 17 minutes). The apparent t½ demonstrates that UGN-101 dissolved gradually, resulting in prolonged exposure of mitomycin following local instillation into the UUT.

UroGen Pharma Ltd.

This was a prospective, open-label, single-arm, pivotal phase study, designed to assess the efficacy, tolerability, and safety UGN-101 treatment administered to the Upper Urinary Tract (UUT).

Upon signing of informed consent, the patients underwent a Screening Visit for eligibility evaluation.

Eligible patients with confirmed Low Grade (LG) noninvasive Upper Tract Urothelial Carcinoma (UTUC) were treated with 6 once-weekly instillations of UGN-101. Tumor response was evaluated at the Primary Disease Evaluation (PDE) Visit, 5 weeks after the last treatment period instillation. Patients who demonstrated complete response (CR) could enter a maintenance period and receive up to11 once-monthly instillations, per investigator modified treatment regimen.

UGN-101 Mitomycin for Pyelocalyceal Solution

This was a prospective, open-label, single-arm, pivotal phase study, designed to assess the efficacy, tolerability, and safety UGN-101 treatment administered to the UUT. Upon signing of informed consent, the patients underwent a Screening Visit for eligibility evaluation.

Eligible patients with confirmed LG noninvasive UTUC were treated with 6 once-weekly instillations of UGN-101. Tumor response was evaluated at the PDE Visit, 5 weeks after the last treatment period instillation. Patients who demonstrated CR could enter a maintenance period and receive up to 11 once-monthly instillations, per investigator modified treatment regimen.

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Israel

Region of Enrollment

Madlen Malinowski

The Primary Efficacy Endpoint Was the Number of Patients Attaining Complete Response (CR) at the End of the Treatment Period (PDE Visit).

Population was analyzed at 12 months post Primary Disease Evaluation (PDE) visit. 8 out of 41 patients had disease recurrence. The Kaplan-Meier estimate of 12 month duration of complete response (CR) rate was 82%.

This was a prospective, open-label, single-arm, pivotal phase study, designed to assess the efficacy, tolerability, and safety UGN-101 treatment administered to the Upper Urinary Tract (UUT).

Upon signing of informed consent, the patients underwent a Screening Visit for eligibility evaluation.

Eligible patients with confirmed low grade (LG) noninvasive Upper Tract Urothelial Carcinoma (UTUC) were treated with 6 once-weekly instillations of UGN-101. Tumor response was evaluated at the PDE Visit, 5 weeks after the last treatment period instillation. Patients who demonstrated CR could enter a maintenance period and receive up to 11 once-monthly instillations, per investigator modified treatment regimen.

The Key Secondary Efficacy Endpoint Was Long-term Durability of Complete Response (CR): Number of Patients Who Maintained CR at 12 Month Post PDE Visit. This Endpoint Was Defined Only for Those Patients Who Achieved CR at the PDE Visit.

Patients reaching CR at PDE evaluated at 3 months post PDE

UGN-101 Patients Evaluated 3 Months Post PDE

Patients reaching CR at PDE evaluated at 6 months post PDE

UGN-101 Patients Evaluated at 6 Months Post PDE

Patients reaching CR at PDE evaluated at 9 months post PDE

UGN-101 Patients Evaluated at 9 Months Post PDE

Patients reaching CR at PDE evaluated at 12 months post PDE

UGN-101 Patients Evaluated at 12 Months Post PDE

Durability of Complete Response (CR) for Each Follow-up Time Point.

This was a prospective, open-label, single-arm, pivotal phase study, designed to assess the efficacy, tolerability, and safety UGN-101 treatment administered to the UUT.

Upon signing of informed consent, the patients underwent a Screening Visit for eligibility evaluation.

Eligible patients with confirmed LG noninvasive UTUC were treated with 6 once-weekly instillations of UGN-101. Tumor response was evaluated at the PDE Visit, 5 weeks after the last treatment period instillation. Patients who demonstrated CR could enter a maintenance period and receive up to11 once-monthly instillations, per investigator modified treatment regimen.

Clinical Benefit for Patients With Partial Response (PR) at the Primary Disease Evaluation (PDE) Visit. Clinical Benefit Endpoint Was Analyzed Using the Intent-to-Treat (ITT) Analysis Set, Including Patients Who Achieved Partial Response at PDE Visit.

The PK profiles of the first UGN-101 instillation in the blood were to be examined for the first 6 patients.

Pharmacokinetic Population

PK Analysis Set: Consisted of patients who signed consent for PK and had sufficient PK data for the determination of PK parameters.

Pharmacokinetic: The PK Profiles of the First UGN-101 Instillation in the Blood Were to be Examined for the First 6 Patients.

Treatment-emergent Adverse Events (TEAEs)

TEAEs related to study drug

TEAEs related to study procedure

TEAEs related to study drug or preocedure

Serious Adverse Events (SAE)

SAEs related to study drug or procedure

This was a prospective, open-label, single-arm, pivotal phase study, designed to assess the efficacy, tolerability, and safety UGN-101 treatment administered to the Upper Urinary Tract (UUT).

Upon signing of informed consent, the patients underwent a Screening Visit for eligibility evaluation.

Eligible patients with confirmed low grade (LG) noninvasive Upper Tract Urothelial Carcinoma (UTUC) were treated with 6 once-weekly instillations of UGN-101. Tumor response was evaluated at the PDE Visit, 5 weeks after the last treatment period instillation. Patients who demonstrated complete response (CR) could enter a maintenance period and receive up to11 once-monthly instillations, per investigator modified treatment regimen.

Safety: Consisted of all patients who enrolled in the study and received at least 1 instillation of UGN-101.

Safety Adverse Event Outcomes: Safety Was Monitored Throughout the Study by Reviewing Adverse Events (AEs).

This was a prospective, open-label, single-arm, pivotal phase study, designed to assess the efficacy, tolerability, and safety UGN-101 treatment administered to the Upper Urinary Tract (UUT).

Upon signing of informed consent, the patients underwent a Screening Visit for eligibility evaluation.

Eligible patients with confirmed low grade (LG) noninvasive Upper Tract Urothelial Carcinoma (UTUC) were treated with 6 once-weekly instillations of UGN-101. Tumor response was evaluated at the Primary Disease Evaluation (PDE) Visit, 5 weeks after the last treatment period instillation. Patients who demonstrated complete response (CR) could enter a maintenance period and receive up to 11 once-monthly instillations, per investigator modified treatment regimen.

Overall Study

Induction Treatment phase:1-3 padeliporfin VTP treatments provided 4 weeks (28 +/-3 days) apart.

Maintenance Treatment Phase: Repeated maintenance VTP treatments during this period will be provided for patients who show evidence of tumor recurrence that is deemed treatable.

During treatment, placement at the target area of an optical light fiber, through the working channel of the ureteroscope. Intravenous administration of padeliporfin at the dose of 3.66 mg/kg infused over 10 minutes. Each target area will be illuminated for 10 minutes.

padeliporfin VTP

Inna Krasnopolskaya, MD

Edward Uchio, MD

Hooman Djaladat, MD

Kenneth Ogan, MD

Nirmish Singla, MD

Prof. Ronald Kaufman, MD

Jonathan Coleman, MD

Eugene Pietzak,, MD

Ahmad Shabsigh, MD

Jay Raman, MD

Robert Grubb, MD

Neal Shore, MD

Vitaly Margulis, MD

Sarah Psutka, MD

Reinhard Aigner, MD

Gautier Marcq, MD

Prof. Marc Colombel, MD, PhD

Jochen Walz, MD

Christian Pfister, MD

Prof. Christian Thomas, MD

Steffen Rausch, MD

Michael Mullerad, MD

Asaf Shvero, MD

Prof. Dan Leibovici, MD

Prof. Mauro Gacci, MD

Prof. Roberto Mario Scarpa, MD

Francesco Soria, MD

Carles Xavier Raventós Busquets, MD

Marco Aller, MD

Francisco Jose Anglada Curado, MD

Inna Krasnopolskaya

This is a phase 3, open label, single arm study of padeliporfin in the treatment of Upper Tract Urothelial Carcinoma (UTUC). The ENLIGHTED study will recruit patients with low-grade non-invasive upper tract urothelial carcinoma in either the kidney or the ureter. Patients will be treated with padeliporfin VTP in two phases: an Induction Treatment Phase and a Maintenance Treatment Phase and will be followed up for up to an additional 48 months in the long term (non intervention) follow up phase with the specific duration depending on the patient's response to treatment

Induction Treament Phase: Patients entered in the study will undergo an induction treatment phase consisting of 1-3 padeliporfin VTP treatments provided 4 weeks (28 +/-3 days) apart. The goal of this induction treatment phase will be to achieve Complete Response (CR) in the involved ipsilateral tract system. During this phase, patients will be treated with padeliporfin VTP to visually identified tumor sites in the calyces, renal pelvis and/or ureter and subsequently examined endoscopically at 28 +/- 3 days post treatment to determine whether the treatment was successful. If CR is not achieved, an additional two treatments of padeliporfin VTP are permitted 28 +/- 3 days apart for a total of up to 3 treatments during the induction treatment phase. The Primary Response Evaluation (PRE) will be performed 28 +/- 3 days after the last VTP treatment, to determine if the treatment was successful at achieving CR defined as: absence of visible tumor on endoscopy, negative urinary cytology by instrumented collection, and no evidence of tumor on biopsy (if feasible). Patients undergoing extirpative surgery of any part of the ipsilateral kidney or ureter for indications related to urothelial cancer will be considered as no longer having CR. If CR is not achieved after 3 treatments with padeliporfin VTP the treatment will be considered unsuccessful and the patient will be discontinued from the Treatment Phases.

Maintenance Treatment Phase: Patients achieving CR at the induction treatment phase will be allowed into the maintenance treatment phase of the study. The patients will then be followed over a period of 12 months post PRE, to assess the duration of response and its safety, and to provide planned maintenance treatment.

Repeated maintenance VTP treatments during this period will be provided for patients who show evidence of tumor recurrence that is deemed treatable as defined by the following criteria: low-grade tumors with the largest tumor (index tumor) betwen 5 mm and 15 mm in diameter, in up to 2 anatomical locations in the calyces, renal pelvis or the ureter with ureter involvement in one anatomical location with no more than 20 mm of contiguous ureteral length). Patients with treatable tumor recurrence post Induction Treatment Phase would be considered as no longer having 'complete response in the entire ipsilateral kidney' and time to recurrence will be recorded. Patients undergoing extirpative surgery of any part of the ipsilateral kidney or ureter for indications related to urothelial cancer will be considered as no longer having CR and time to this event will be recorded.

Long Term Follow-up Phase: Patients completing the 12 months of the maintenance treatment phase of the study, could be followed for an additional 48 months to monitor for disease related outcomes and VTP treatment related adverse events with the specific duration depending on the patient's response to treatment. No additional padeliporfin VTP treatment will be administered during this phase. Patients completing the maintenance phase of the study who are in CR in V3 will undergo additional assessments 18 and 24 months (+/- 1 month) post-PRE and annually thereafter and for up to 5 years post PRE or until recurrence, progression, death or loss to follow up, to document safety and ongoing response.

Phase III, single arm, non randomized, multicenter trial

ENdoluminal LIGHT ActivatED Treatment of Upper Tract Urothelial Cancer (ENLIGHTED) Study

Multicenter Phase 3 Pivotal Study to Evaluate the Safety and Efficacy of TOOKAD (Padeliporfin) Vascular Targeted Photodynamic Therapy in the Treatment of Low Grade Upper Tract Urothelial Cancer

Primary efficacy outcome is the absence of UTUC tumors in the entire ipsilateral calyces renal pelvis and ureter on endoscopic evaluation at the time of Primary Response Evaluation (PRE) (28 +/- 3 days post last treatment) during padeliporfin VTP induction treatment phase. This outcome will be determined dichotomously as either failure or success in achieving complete response.

· Complete Response will be defined as absence of disease based on:

* absence of visual tumor on endoscopy
* no evidence of tumor on biopsy (if feasible)
* negative urinary cytology by instrumented collection

The duration of response at the entire ipsilateral kidney will be defined as absence of disease in the entire ipsilateral calyces, renal pelvis and ureter, based on:

* instrumented cytology
* visually on endoscopy
* biopsy pathology (if feasible) as will be measured at the 12 months maintenance treatment visit post PRE

The duration of response at the entire ipsilateral kidney will be defined as absence of disease in the entire ipsilateral calyces, renal pelvis and ureter, based on:

* instrumented cytology
* visually on endoscopy
* biopsy pathology (if feasible) as will be measured at the 3, 6, 9 months maintenance treatment visits post PRE

Duration of response at the Treatment Area of the ipsilateral kidney will be defined as absence of disease in the ipsilateral Treatment Area, based on:

* instrumented cytology
* visually on endoscopy
* biopsy pathology (if feasible) as will be measured at the 3, 6, 9, and 12 months maintenance treatment visits post PRE

Overall renal functional outcome will be measured at the 6 and 12 months maintenance treatment visits post PRE, and will be evaluated by comparing pre-treatment and 12-month estimated glomerular filtration rate (eGFR), calculated from serum creatinine levels, using the CKD-Epi method including:

* Absolute change in eGFR as well as categories of CKD will be utilized based on KDIGO 2012 criteria
* Description will include change in eGFR, change in CKD stage/risk category

Kidney organ loss or preservation will be recorded at each maintenance treatment visit post PRE at 3, 6, 9, and 12 months Maintenance Treatment visits, and will describe the reasons for organ preservation or loss. A radical nephroureterectomy, nephron-sparing surgery for UTUC or ureterectomy will be considered as organ loss.

PathologicalPathological evaluation of response will be performed in kidney tissue of patients that will undergo kidney surgical removal (kidney sparing, or radical nephroureterectomy) following at least one padeliporfin VTP treatment

Patients with existing ureteral obstruction and/or existing ureteral stent will be permitted with radiographic evidence of pre-existing obstruction documented, to demonstrate the site and degree of obstruction with retrograde pyelography at baseline (prior to treatment) and will be repeated and recorded at 12 months maintenance treatment visit (post treatment) which will further be supported with CT Urogram results at 12 months to demonstrate the site and degree of obstruction using standard nomenclature.

The duration of response in the ipsilateral kidney and treatment area will be defined as absence of disease, based on:

* instrumented cytology
* visually on endoscopy
* biopsy pathology (if present and performed)

Kidney organ loss or preservation will be recorded and will describe the reasons for organ preservation or loss. A radical nephroureterectomy, nephron-sparing surgery for UTUC or ureterectomy will be considered as organ loss and a pathology report of the removed tissue will be recorded (if available or feasible)

Overall renal functional outcome will be evaluated by estimated glomerular filtration rate(eGFR) using CKD-Epimethod

Safety follow up based and recording of adverse events

Blood,tumor and cytology samples will be collected, centrally stored and later submitted for tumor genomic sequencing studies to explore the tumor genomic alterations, and mutation status as biomarkers with association to treatment response and progression events such as recurrence, grade transformation, increased stage and metastases.

Patients with moderate hepatic impairment, will undergo a pharmacokinetic evaluation, blood samples will be collected to evaluate Cmax

Patients with moderate hepatic impairment, will undergo a pharmacokinetic evaluation, blood samples will be collected to evaluate Tmax

Patients with moderate hepatic impairment, will undergo a pharmacokinetic evaluation, blood samples will be collected to evaluate T1/2

Patients with moderate hepatic impairment, will undergo a pharmacokinetic evaluation, blood samples will be collected to evaluate AUC

Patients with moderate hepatic impairment, will undergo a pharmacokinetic evaluation, blood samples will be collected to evaluate CL

PrimeVigilance

ICON plc

Steba Biotech S.A.

Blood and Lymph Conditions

Immune System Diseases

Symptoms and General Pathology

Lymphoma

Lymphoma, Non-Hodgkin

Leukemia

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Follicular

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Leukemia, Lymphoid

Hematologic Diseases

Chronic Disease

Disease Attributes

Lymphosarcoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Follicular Lymphoma

Analgesics

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Antirheumatic Agents

Antibodies

Antibodies, Monoclonal

Mitoxantrone

Fludarabine

Fludarabine phosphate

Dexamethasone

Rituximab

Dexamethasone acetate

Immunoglobulins

Pixantrone

Antineoplastic Agents, Immunological

Immunologic Factors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Pixantrone (BBR 2778)

fludarabine

dexamethasone

rituximab

Scott Stromatt, MD

The aim of this trial is to determine the appropriate dose of pixantrone to be used in this combination and obtain data on the combination's safety and activity profile.

The FND-R regimen is commonly used in the treatment of indolent Non-Hodgkin's lymphoma (NHL) and contains the chemotherapy agents mitoxantrone, fludarabine, dexamethasone (a steroid) and the monoclonal antibody rituximab. In this trial we are replacing mitoxantrone with pixantrone, an agent with a similar chemical structure (both agents are DNA intercalators). The trial is being run in patients with relapsed or refractory indolent NHL and aims to define the appropriate dose of pixantrone to be used in this combination, as well as to obtain data on pixantrone's safety and activity profile in combination with these drugs.

This trial is expected to recruit up to 30 patients in the USA. Patients will be treated with the drug combination for up to eight months and then followed closely in the four-week period after the last administration. After that, patients will receive physician check-ups every three months.

Dose Ranging Trial for Pixantrone in the FND-R Variant Regimen in Indolent Non-Hodgkin's Lymphoma

A Phase I Trial of BBR 2778 in Combination With Fludarabine, Dexamethasone and Rituximab in the Treatment of Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma

CTI BioPharma

Gabriella Camboni, M.D.

The purpose of this study is to determine whether combining pixantrone (BBR 2778, INN name pending) with the monoclonal antibody rituximab, leads to an increase in the period of patients' remission, compared to rituximab alone.

This trial is being conducted in patients with indolent (or low-grade) non-Hodgkin's lymphoma, who have either relapsed or been refractory to previous treatment.

Pixantrone belongs to the DNA intercalator family of chemotherapy agents, which includes anthracyclines. DNA intercalators are commonly used to treat patients with indolent NHL, often in combination with the monoclonal antibody rituximab. This study represents the first large-scale, comparative trial in indolent NHL, designed to determine whether the response rate and time to tumour progression in patients treated with a combination of rituximab and a DNA intercalator, is significantly higher than seen in patients treated with rituximab alone.

This trial is randomized and controlled, which means that participating patients will be randomly assigned to one of two treatment groups:

1. Patients treated with both pixantrone and rituximab, in combination
2. Patients treated with only rituximab

This trial is expected to recruit around 800 patients in the US, Europe and Israel, with 400 patients recruited to each group.

Patients will be treated for around 18 weeks and will recieve regular physician monitoring for five years from the end of treatment.

Comparative Trial for Pixantrone in Combination With Rituximab in Indolent Non-Hodgkin's Lymphoma

An Open-Label, Randomized, Phase III Comparative Trial of BBR 2778 + Rituximab Versus Rituximab in the Treatment of Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma (NHL)

* objective overall response rate (ORR; CR + PR)
* objective complete response rate (CRR)
* rate of molecular remission
* time to response
* time to complete response
* duration of response
* Time to Tumor Progression requiring treatment
* Quality-Adjusted Time To Progression (QATTP)
* overall survival
* disease-specific survival
* safety/tolerability

Recurrence

The Mitomycin C (MMC) concentration of UGN-101 to be used in this trial will be 4 mg MMC per 1 mL of TC-3 gel, the maximum dose is 15ml. 3-6 once weekly intravesical instillations for the ablation treatment.

Treatment with UGN-101 once weekly for a total of 3-6 times; in a retrograde fashion.

Ifat Klein, Phd

This trial is designed to evaluate the efficacy and safety of UGN-101 administered to the upper urinary tract (UUT) in patients who were treated in Trial TC-UT-03, found to be a complete response (CR) at the Primary Disease Evaluation (PDE) 1 Visit and are subsequently found to have a documented recurrence of low grade (LG) upper tract urothelial carcinoma (UTUC) at follow up (FU).

This is an open-label, single-arm, Phase 3b multicenter extension trial, designed to evaluate the efficacy and safety of UGN-101 administered to the UUT in patients who were treated in Trial TC-UT-03, found to be a CR at the PDE 1 Visit, and are subsequently found to have a documented recurrence of LG UTUC at FU.

Upon signing of informed consent, the patients will undergo their routine ureteroscopy to assess durability. A biopsy will be performed at Visit 0, if appropriate, to confirm evidence of tumor. If a high grade (HG) UTUC is confirmed by biopsy and/or cytology, the patient will be excluded from the retreatment trial. Eligible patients with confirmed LG non-invasive UTUC will be treated with 3 to 6 once-weekly instillations of UGN-101 in a retrograde fashion, per investigator's discretion.

Five weeks (± 1 week) following the last Investigational product (IP) treatment, the patient will be assessed for efficacy and safety at the PDE 2 Visit. At this visit, the patient will undergo ureteroscopy and any remaining lesions will be biopsied, and UUT urine wash will be collected for cytology.

Patients demonstrating CR at the PDE 2 Visit will undergo FU visits at 3, 6, 9, and 12 months (± 2 weeks) following the PDE 2 Visit.

The trial will be approximately 15 months, per patient: a 3- to 6-week treatment period, followed by 4 to 6 weeks post-treatment leading up to the PDE 2 Visit, and a 12-month FU post PDE 2 Visit. This trial will follow the Steering Committee, and a Data Monitoring Committee (DMC) has been assigned as established for the primary trial TC-UT-03.

Efficacy and Safety of UGN-101 in Recurrent Patients

A Phase 3b Multicenter Extension Trial Evaluating the Efficacy and Safety of UGN-101 (Mitomycin Gel) for Instillation on Ablation of Upper Urinary Tract Urothelial Carcinoma in Recurrent Patients From Trial TC-UT-03

Adverse events (AEs) analyses will include only Treatment Emergent Adverse Events (TEAEs), namely, those events which started on the day of first trial IP administration or afterwards.

The incidence (no. of patients) of TEAEs will be provided when broken down by System Organ Class (SOC) and by Preferred Term (PT) according to MedDRA dictionary;

* Breakdowns of TEAEs by all AEs attributes will also be provided;
* Breakdowns of TEAEs by age, sex and volume of instillation will also be provided;
* The incidence of serious TEAEs will be provided when broken down by System Organ Class (SOC) and by Preferred Term (PT) according to MedDRA dictionary as well as by serious adverse events (SAEs) attributes and by age, sex, and volume of instillation. SAEs will also be listed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The OLYMPUS Study - Optimized DeLivery of Mitomycin for Primary UTUC Study	NCT02793128	Carcinoma, Tran... Transitional Ce...	UGN-101 instill...	18 Years -	UroGen Pharma Ltd.
ENdoluminal LIGHT ActivatED Treatment of Upper Tract Urothelial Cancer (ENLIGHTED) Study	NCT04620239	Transitional Ce...	padeliporfin VT...	18 Years -	Steba Biotech S.A.
Dose Ranging Trial for Pixantrone in the FND-R Variant Regimen in Indolent Non-Hodgkin's Lymphoma	NCT00060684	Lymphoma, Low-G... Lymphoma, Small... Lymphoma, Mixed... Lymphoma, Small...	Pixantrone (BBR... fludarabine dexamethasone rituximab	18 Years -	CTI BioPharma
The OLYMPUS Study - Optimized DeLivery of Mitomycin for Primary UTUC Study	NCT02793128	Carcinoma, Tran... Transitional Ce...	UGN-101 instill...	18 Years -	UroGen Pharma Ltd.
Comparative Trial for Pixantrone in Combination With Rituximab in Indolent Non-Hodgkin's Lymphoma	NCT00060671	Lymphoma, Folli... Lymphoma, Mixed... Lymphoma, Small... Lymphoma, Low-G...	rituximab Pixantrone (BBR...	18 Years -	CTI BioPharma
ENdoluminal LIGHT ActivatED Treatment of Upper Tract Urothelial Cancer (ENLIGHTED) Study	NCT04620239	Transitional Ce...	padeliporfin VT...	18 Years -	Steba Biotech S.A.
Efficacy and Safety of UGN-101 in Recurrent Patients	NCT04006691	Carcinoma Transitional Ce... Transitional Ce...	UGN-101 instill...	18 Years -	UroGen Pharma Ltd.

Spots Global Cancer Trial Database for low grade

Every month we try and update this database with for low grade cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for low grade

Every month we try and update this database with for low grade cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for low grade cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.