Non-Muscle Invasive Bladder Cancer (NMIBC) / urinary bladder cancer / oncology Cancer Malignant neoplasm of bladder
Conditions
Interventions
An open-label Phase I dose escalation trial that will follow a standard escalation design with cohorts of 3 patients per dose level. TMX-101 will be given once a week for 6 weeks.
Two-three weeks be
cytology, TUR and biopsies will be performed. Histology will be performed to confirm inclusion criteria. Patients eligible for the Effective Biological Dose assessment (EBD) assessment (Part 2) will n
Sponsors
Telormedix SA (Switzerland)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The study population will consist of patients with non-muscle invasive bladder cancer (NMIBC) who have undergone Transurethral resection (TUR). A complete TUR will be performed in patients entering the first part of the study, while in patients entering the second part of the study a marker lesion will be left for assessment after the TUR procedure. All patients 1. Age = 18 years. 2. Performance status: ECOG 0-1. 3. Subjects who have read and understood the informed consent form and are willing and able to give informed consent. Subjects who fully understand the requirements of the trial and are willing to comply with all trial visits and assessments. 4. Women of childbearing potential must have a negative blood pregnancy test at the screening visit. For the purposes of this trial, ?women of childbearing potential? is defined as: ?All female subjects after puberty unless they are post-menopausal for at least two years, are surgically sterile or are sexually inactive?. 5. Female subjects of childbearing potential and male subjects with female partners of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for 2 weeks prior to, during and four weeks after the last dose trial medication. ?Adequate contraception? is defined as follows: two barrier methods, or one barrier method with a spermicide or intrauterine device. Patients to enter the first part of the study: 1. Histologically confirmed diagnosis of urothelial carcinoma of the urinary bladder stage Ta with low and high histological grade or T1 with low histological grade. 2. Complete removal of tumours through TUR procedure. Patients to enter the second part of the study: 1. Histologically confirmed diagnosis of urothelial carcinoma of the urinary bladder stage Ta or T1 with low histological grade. 2. Prior to TUR, multiple tumours but not more than seven. 3. One marker lesion left for assessment after TUR procedure, between 0.5 to 1.0 cm in diameter, documented with video or photo.
Exclusion criteria
Exclusion criteria: Patients in the first part of the study: 1. Current urinary tract T1 high grade tumour, previous or current history of carcinoma in situ, muscle invasive disease (T2 or higher). 2. Current high grade urinary cytology in subjects with T1 tumour. Patients in the second part of the study: 1. Current urinary tract Ta high grade tumour, previous or current history of T1 high grade tumour, carcinoma in situ, muscle invasive disease (T2 or higher). 2. Current high grade urinary cytology 3. Subjects who require immediate complete TUR, as judged by the investigator. All Patients 1. Any prior intravesical BCG or any other immunotherapy within the last 24 months. 2. Previous intravesical treatment with chemotherapy agents within 6 months of entry into the study. 3. Subjects who cannot hold instillation for at least one hour. 4. Subjects who cannot tolerate intravesical administration or intravesical surgical manipulation. 5. Current or prior pelvic external beam radiation or pelvic brachytherapy. 6. Existing urinary tract infections or recurrent severe bacterial cystitis. 7. History of disease of the upper urinary tracts (e.g. vesico-urethral reflux, indwelling urinary stent, UT stones). 8. Bone marrow impairment as evidenced by Haemoglobin 1.5 x ULN, and/or calculated creatinine clearance 1.5 x ULN, or AST/ALT > 2.5 x ULN. 11. Bleeding disorders as evidenced by INR > 1.5 x ULN. 12. Immunosuppressed patients or patients receiving immunosuppressive therapy or who are otherwise immunocompromised. 13. Known HIV positivity, active hepatitis C, or active hepatitis B. 14. Any other active malignancy within 5 years except study indication, basal or squamous cell skin cancers and cured prostate cancer (PSA below 0.2 ng/mL). 15. Clinically significant active infections within 4 weeks before initial treatment administration. 16. Any medical or psychiatric condition which, in the opinion of the investigator, might impair the subject?s well being or preclude him from adhering to the protocol or completing the trial as per protocol. 17. Suspected hypersensitivity to imidazoquinoline compounds, poloxamer 407, hydroxy propyl betacyclodextrin, lactic acid. 18. Women who are pregnant or breast feeding. 19. Participation in any other protocol involving administration of an investigational agent within 3 months prior to entering this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. The number and proportion of subjects experiencing treatment-emergent adverse events (TEAE). 2. The number and proportion of subjects experiencing clinically significant changes in a laboratory parameter and/or vital signs judged to be related to the trial medication. 3. The number and proportion of subjects experiencing at least a Dose-Limiting Toxicity (DLT) over the first 3-week cycle (from Day 0 to 21) at each dose level. 4. The number and proportion of subjects with clinical benefit (defined as CR) based on the tumour evaluation 2-4 weeks after the last instillation (6th instillation). Safety measures will be assessed at each patient visit throughout the study schedule. Measures are Adverse Events assessments during each study visit; in addition Investigations like physical exam or Vital signs, Blood and Urine parameters assessments at fixed study visits. | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics Plasma and urine PK parameters of TMX-101 and its main metabolites. Measured at several timepoints in selected patients. Pharmacodynamic Values and changes over time in pharmacodynamic markers in urine and in blood. Measured at several timepoints in selected patients. Anti-tumor activity The anti-tumour activity of TMX-101 will be assessed by summarizing the number and percent of subjects by tumour responses including Complete Response (CR), No Response (NR), Progressive Disease (PD) and Not Evaluable (NE) after 6 weeks of treatment for Part 2 only. Pharmakokinetic (PK) and Pharmacodynamic (PD) assessments by blood analysis are being performed in defined patients at all visits until end of individual treatment period. Urine assessments on PK and PD are being assessed from each patient at all visits until end of treatment period. The anti-tumor activity will be assessed by TUR, cystoscopy and Urine cytology occurring during screening visit. Cystoscopy and Cytology will be repeated at the post-treatment activity assessment visit and at the 1-year Follow-up visit. If cystoscopy reveals new tumors, a TUR will be planned and histology performed. | — |
Countries
Germany, Netherlands
Outcome results
None listed