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

Symptoms and General Pathology

Digestive System Diseases

Recurrence

Colorectal Neoplasms

Adenocarcinoma

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Disease Attributes

Formaldehyde

Survivors of T1 colorectal cancer who developed recurrent colorectal cancer within 36 months from primary tumor treatment, in the first cohort

Survivors of T1 colorectal cancer who did not develop recurrent colorectal cancer within 36 months from primary tumor treatment, in the first cohort

Survivors of T1 colorectal cancer who developed recurrent colorectal cancer within 36 months from primary tumor treatment, in the second cohort

Survivors of T1 colorectal cancer who did not develop recurrent colorectal cancer within 36 months from primary tumor treatment, in the second cohort

A panel of microRNA and messenger RNA, whose expression level is tested in macro-dissected formalin-fixed and paraffin-embedded (FFPE) samples derived from the primary tumor, with reverse transcriptase quantitative polymerase chain reaction (RT-qPCR)

Tw1CE

Ajay Goel, PhD

Takayuki Noma, MD

Alessandro Mannucci

Mitsuo Shimada, PhD

Katsuki Miyazaki

Yuma Wada, PhD

Mistuo Shimada, PhD

Maria Pellise

Karmele Saez de Gordoa

María Daca

Francesc Balaguer

Tumor recurrence significantly affects survival rates following the local resection of submucosal colorectal cancers (T1 CRC). Despite this, there are currently no reliable biomarkers established to predict recurrence in T1 CRC.

This study seeks to improve the prediction of recurrence-free survival in individuals who have survived T1 CRC.

The incidence of invasive submucosal colorectal cancer (T1 CRC) is increasing, likely as a reflection of improved screening and endoscopy use. Current treatment options for T1 CRC focus on less invasive methods (i.e., endoscopic submucosal dissection), and treatment decisions are based on the risk of lymph node metastasis (LNM). Up to 70-80% of T1 CRC patients may undergo surgery, with adjuvant chemotherapy recommended only for those with LNM.

However, current clinical practice guidelines are considered to be overly aggressive and recommend the administration of aggressive treatment to many patients who may be cured with non-invasive therapy alone. This results in the overtreatment of many patients, especially those that are currently defined as 'high-risk' T1 CRC. Existing surveillance methods may not adequately predict the prognosis of T1 CRC, lacking established biomarkers for assessing disease-free survival.

This study seeks to validate tissue-based biomarkers (micro-RNA and messenger RNA) that are associated with tumor recurrence after curative resection. The identification of patients at high risk of recurrence may help in the selection of patients who truly benefit from additional oncologic surgery or adjuvant therapy. Previous research by this group has identified miRNA signatures for detecting postoperative tumor recurrence and metastasis in CRC, highlighting their potential as biomarkers for disease progression.

Formalin-fixed, paraffin-embedded slide from the primary tumor

Predicting Local and Distant Recurrence in T1 Colorectal Cancer

Predicting Recurrence After Curative-Intent Resection of T1 Colorectal Cancer With Transcriptomics

Data collected for the study will be made available to others, including de-identified participant data, at publication, via a signed data access agreement and at the discretion of the investigators' approval of the proposed use of such data.

Time from curative-intent resection to the development of recurrence (or death)

City of Hope Medical Center

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Carcinoma, Squamous Cell

Neoplasm Metastasis

Head and Neck Neoplasms

Mouth Neoplasms

Squamous Cell Carcinoma of Head and Neck

Oropharyngeal Neoplasms

Neoplasms, Squamous Cell

Neoplastic Processes

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Mouth Diseases

Oral Cancer

Lip and Oral Cavity Cancer

Pembrolizumab

Cisplatin

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Intensity-modulated radiation therapy to 70 Gy in 33-35 fractions over 6.5 weeks plus concurrent cisplatin 100 mg/m2 every 3 weeks for 3 cycles (7 weeks)

Intensity-modulated radiation therapy to 70 Gy in 33-35 fractions over 6.5 weeks plus concurrent and adjuvant pembrolizumab 200 mg IV infusion every 3 weeks x 20 cycles

Pembrolizumab 200 mg IV infusion every 3 weeks x 20 cycles

Radiation therapy

Loren Mell, MD

Gerald Henderson

Alysha Zeoli

Ricklie Julian, MD

Khushbu Singh, MBBS, CCRP

Jennifer Pope, CCRP

Melissa Young, MD, PhD

Elisa Lemerond

Jimmy Caudell, MD

Melissa Butler

Douglas Adkins, MD

Aubrey Hamilton

Sarah Wilson

Trisha Wise-Draper, MD, PhD

Kathy Taylor

Mike Gibson, MD

The purpose of this study is to compare any good or bad effects of using pembrolizumab (an experimental drug) and radiation therapy (RT), compared to using cisplatin chemotherapy and radiation therapy (RT) in the treatment of patients with head and neck squamous cell carcinoma (HNSCC).

This study is a prospective, multi-institutional, open-label, randomized phase II trial that will evaluate the efficacy of concurrent and adjuvant pembrolizumab with radiation therapy (RT) versus RT plus cisplatin in intermediate/high-riskp16-positive locoregionally advanced head and neck squamous cell carcinoma (HNSCC). The primary endpoint is progression-free survival (PFS).

Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer

Phase II Randomized Trial of Radiotherapy With Concurrent and Adjuvant Pembrolizumab (Keytruda®) Versus Concurrent Chemotherapy in Patients With Advanced/Intermediate-Risk p16+ Head and Neck Squamous Cell Carcinoma (KEYCHAIN)

compare the outcomes with RT/pembrolizumab in patients with tumors as a function of PD-L1 expression.

time from randomization to progression/relapse or death from any cause.

time from randomization to death from any cause

Toxicities due to therapy occurring within 3 months of therapy completion based on CTCAE criteria using questionnaires

Toxicity due to therapy occurring greater than 3 months after completion of therapy based on CTCAE criteria using questionnaires

Local and regional and distant recurrence of cancer and causes of death from competing events

Merck Sharp & Dohme LLC

Director, Division of Clinical and Translational Research/ Department of Radiation Medicine

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.

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 Frequency (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 Frequency 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.

Changes from baseline in laboratory values and incidence of measurements defined as Potentially Clinically Significant (PCS) will include the following:

Complete blood count (CBC, including red blood, cell indices, and white blood cell differential, Platelet count), Creatinine, Blood urea nitrogen, Uric acid, Sodium, Potassium, Phosphorus, Calcium, serum glutamate oxaloacetate transaminase/aspartate aminotransferase (SGOT/AST), serum glutamate pyruvate transaminase/Alanine transaminase (SGPT/ALT), gamma-glutamyl transferase (GGT), Alkaline phosphatase, Total Bilirubin, Direct Bilirubin, Albumin, Total protein, Prothrombin Time and International Normalized Ratio, and Urinalysis (Specific gravity, power of hydrogen (pH), Glucose, Urobilinogen, Bilirubin, Blood, Protein, Nitrites, Leukocyte Esterase, Microscopic examination, Bacteriuria (if required) and White blood cells)

Changes from baseline in vital signs assessments values and incidence of measurements of Potential Clinical Significance (PCS) will include blood pressure, pulse, and temperature

Any clinically-relevant changes occurring during the trial visit will be recorded in the AE sections of the case report form (CRF). Full general physical examination will be done on visits 0, 7, and 11 Urology-oriented physical examinations will be done on visits 0, 7, 8, 9, 10, and 11.

Full physical examination findings are composite outcome measure consisting of multiple measures:

General appearance, Cardiovascular system, Respiratory system, HEENT (head, eyes, ears, nose, and throat) and neck, Abdomen Extremities and Neurologic system Skin

Urology-Oriented physical examination findings are composite outcome measure consisting of multiple measures:

Urethral meatus, Perineal skin and mucus membranes Scrotum and testes (for male patients), Lymphadenopathy, Rectal examination (Screening visit only) Bimanual examination (female patients - Screening visit only)

Complete response defined dichotomously as "Success" if CR was confirmed at the end of the treatment period (PDE 2 Visit), and "Failure" otherwise.

This endpoint is defined only for those patients demonstrating CR at the PDE 2 Visit.

Respiratory Tract (Lung and Bronchial) Diseases

Laryngeal Diseases

Laryngeal Neoplasms

Respiratory Tract Diseases

Respiratory Tract Neoplasms

Laryngeal Cancer

Hypofractionated radiotherapy 58.08Gy/16 fractions to affected vocal cord plus margins to account for motion and setup errors using IMRT/VMAT technique

Radiotherapy 63Gy/28 fractions to whole larynx from lower border of hyoid bone to lower border of cricoid cartilage using IMRT/VMAT technique

Only the affected vocal cord with additional margin to account for motion and setup errors will receive 58.08Gy/16 fractions using IMRT/VMAT technique

Hypofractionated single vocal cord irradiation

The whole larynx from lower border of hyoid bone to lower border of cricoid cartilage will receive 63Gy/28 fractions using IMRT/VMAT technique

Whole laryngeal radiotherapy

Mohamed Mortada Elsharief

Tarek Shouman

The primary objective of this prospective randomized clinical trial is to assess non inferiority in terms of local control achieved with single vocal cord hypofractionated radiotherapy compared to standard of care whole laryngeal radiotherapy in patients with T1aN0 glottic cancer . Secondary objectives include overall survival rate and to compare the Voice Handicap Index score between the 2 arms as well as acute and late toxicities. Patients are randomized in 1:1 ratio.

Most laryngeal cancers present in early stage and more than two thirds of it occur in the glottic region(T1-T2). Early glottic carcinoma is historically treated with conventional radiotherapy using large box fields (from lower border of hyoid to lower border of cricoid), using wedged parallel opposed photon beams. In spite of good local control rate of more than 90% for T1a glottic cases, the tumor-free contralateral vocal cord, arytenoids, thyroid cartilage, and all muscles responsible for opening and closing the vocal cords, the swallowing muscles, carotid arteries and thyroid gland are exposed to high radiation doses (fully or partially) which could lead to an increased probability of complications that negatively influence the quality of life of these patients. Typical complications have involved voice/ speech impairment, diet problems (swallowing, trismus), arytenoids edema, an increased risk of strokes, and reduced treatment options for previously irradiated patients. Many studies showed that increasing fraction size and shortening the overall treatment time (hypofractionated radiotherapy) could result in better local control of T1 glottic cancer The use of 63Gy/28 Fractions(Fx) showed superior local control compared with conventional use of 66Gy/33Fx with shorter overall treatment time. Based on this study this dose is the standard in our institute. In contrast to the traditional radiotherapy principle to treat the whole larynx, surgical laser excision of T1a glottic cancer involves removal of gross tumor with minimal, often sub-millimeter, excisional margins with good oncological outcome and good quality of voice. Similar to this surgical concept and with modern radiotherapy IMRT/VMAT technique, the approach of single vocal cord irradiation (SVCI) was introduced. A study of 30 patients with T1a glottis cancer treated by image guided vocal cord radiotherapy was published in 2015 and it showed 100% local control at 2 years and with no grade 3 toxicities reported and better quality of voice when compared to historical cohorts Dosimetric analysis showed that IMRT resulted in markedly reducing the dose to contralateral cord, arytenoids, thyroid cartilage, inferior constrictor muscle and carotid arteries. To date no prospective phase 3 trial was done to compare treatment outcome and toxicity profile of vocal cord only hypofractionated radiotherapy vs traditional whole laryngeal radiotherapy.

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.
Predicting Local and Distant Recurrence in T1 Colorectal Cancer	NCT06314971	Colorectal Canc... Colorectal Neop... Colorectal Aden... Colorectal Canc... Colorectal Neop... Colorectal Canc...	Tw1CE	18 Years -	City of Hope Medical Center
Predicting Local and Distant Recurrence in T1 Colorectal Cancer	NCT06314971	Colorectal Canc... Colorectal Neop... Colorectal Aden... Colorectal Canc... Colorectal Neop... Colorectal Canc...	Tw1CE	18 Years -	City of Hope Medical Center
Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer	NCT03383094	Head and Neck S... Cancer Cancer of Head ... Cancer, Advance... Cancer, Metasta... Tumor Tumor Recurrenc... Tumor Neck Tumor Metastasi... Oral Cancer Oropharyngeal C... Oropharynx Canc... Oropharynx Canc... Oropharynx Canc... Oropharynx Canc...	Pembrolizumab Radiation thera... Cisplatin	18 Years -	University of California, San Diego
The OLYMPUS Study - Optimized DeLivery of Mitomycin for Primary UTUC Study	NCT02793128	Carcinoma, Tran... Transitional Ce...	UGN-101 instill...	18 Years -	UroGen Pharma Ltd.
Efficacy and Safety of UGN-101 in Recurrent Patients	NCT04006691	Carcinoma Transitional Ce... Transitional Ce...	UGN-101 instill...	18 Years -	UroGen Pharma Ltd.
Vocal Cord vs Whole Laryngeal Radiotherapy for T1aN0 Glottic Cancer	NCT05679856	Larynx Cancer S... Glottic Carcino...	Hypofractionate... Whole laryngeal...	18 Years -	National Cancer Institute, Egypt

Spots Global Cancer Trial Database for t1

Every month we try and update this database with for t1 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 t1

Every month we try and update this database with for t1 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 t1 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.