Non-Muscle-Invasive Bladder cancer
Conditions
Interventions
Each subject will receive a first cycle of TMX-101 comprising of one dose given
once a week for three consecutive weeks. After the end of the first cycle (day
0 to day 21) if no serious toxicity is
Sponsors
Telormedix SA
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: (a) Age at least 18 years. (b) Histologically confirmed diagnosis of urothelial carcinoma of the urinary bladder stage Ta or T1 with low histological grade. (c) Performance status: ECOG 0-1 (d) 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. (e) 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*. (f) 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: (g) Complete removal of tumours through TUR procedure Patients to enter the second part of the study: (h) Prior to TUR multiple tumours but not more than seven. (i) 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: (a) Previous or current history of urinary tract high grade tumour, carcinoma in situ, muscle invasive disease (stage T2 or higher). (b) Any prior intravesical BCG or any other immunotherapy within the last 24 months. (c) Previous intravesical treatment with chemotherapy agents within 6 months of entry into the study. (d) Subjects who cannot hold instillation for at least one hour. (e) Subjects who cannot tolerate intravesical administration or intravesical surgical manipulation. (f) Current or prior pelvic external beam radiation or pelvic brachytherapy. (g) Existing urinary tract infections or recurrent severe bacterial cystitis. (h) History of disease of the upper urinary tracts (e.g. vesico-urethral reflux, indwelling urinary stent, UT stones). (i) High grade urinary cytology. (j) 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. (m) Bleeding disorders as evidenced by INR > 1.5 x ULN. (n) Immunosuppressed patients or patients receiving immunosuppressive therapy or who are otherwise immunocompromised. (o) Known HIV positivity, active hepatitis C, or active hepatitis B. (p) Any other active malignancy except study indication and basal or squamous cell skin cancers. (q) Clinically significant active infections within 4 weeks before initial treatment administration. (r) 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. (s) Suspected hypersensitivity to imidazoquinoline compounds, poloxamer 407, hydroxy propyl betacyclodextrin, lactic acid. (t) Women who are pregnant or breast feeding. (u) 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 |
|---|---|
| The primary study parameter is regarding Safety: During this study, patients will be treated in cohorts of three per dose level until the OBD or MTD is reached, whichever occurs first. The number of patients will increase to six in those cohorts where one out of three patients develops Dose Limited Toxicity (DLT). The safety of the OBD and/or the MTD will be confirmed in at least 6 patients who have received two cycles of TMX-101 therapy. To ensure safety, each dose level will start with one patient receiving a cycle of TMX-101. The other two patients from the same cohort will start the therapy not less than one week later as long as no serious toxicity is observed in the first patient after the first instillation. If none of the three patients develops DLT, the dose will be escalated. If two or more patients experience DLT, further dosing at that dose level will stop and the dose level immediately below will be considered to be the MTD. Should only one out of three patients at the same dose level experience DLT, the number of patients treated at this dose level will be expanded to six. Provided none of the additional three patients experiences DLT, the dose will be escalated further; otherwise the escalation will stop and the dose immediately below will be deemed to be the MTD. - DLT is defined as any of the following toxicities occurred during the first cycle at any dose level which the investigator and/or the sponsor judge to be related to the trial medication. o Any grade 3 or higher toxicity. o Any treatment delay >= 21 days due to drug-related adverse events. - The OBD is defined as Complete Response (CR) (total disappearance of a marker lesion and the absence of new tumours at other sites), as observed in at least three patients. As these patients can be from the different dose levels, the OBD will be considered to be at the highest dose level at which these activities are observed. - The MTD is defined as the highest dose level a | — |
Secondary
| Measure | Time frame |
|---|---|
| (a) Safety - The number and proportion of subjects experiencing treatment-emergent adverse events (TEAE). - 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. (b) Pharmacokinetics - Plasma and urine PK parameters of TMX-101 and its main metabolites. (c) Pharmacodynamic - Values and changes over time in PD markers in urine, blood, and in bladder/tumour tissue samples (d) To describe the relationship between tumour characteristics (e.g. tumour immunohistochemistry) and biological activity. (e) To assess the disease recurrence and progression to muscle invasive disease within 1 year. | — |
Countries
Netherlands
Outcome results
None listed