Non-muscle invasive bladder cancer awaiting transurethral surgery
Conditions
Interventions
Product Name: alpha1H
Pharmaceutical Form: Intravesical solution
INN or Proposed INN: Alpha1 peptide
Other descriptive name: ALPHA1 PEPTIDE
Concentration unit: mg/ml milligram(s)/millilitre
Concentrat
Sponsors
Hamlet Pharma AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Signed and dated informed consent. Patient with non-muscle invasive papillary bladder cancer (NMIBC) based on cystoscopy appearance, on the waiting list for TURB. Male and female subjects, 18 years or older. Negative pregnancy test in women of childbearing potential. Appropriate methods of contraception in women of childbearing potential during study. Patients should be able to keep the content of the bladder for at least one hour. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: Patient with a previous history of muscle invasive bladder cancer. Patient with a history of NMIBC with an interval shorter than 6 months after previous TURB. Previous intravesical BCG immunotherapy in the last 12 months. Previous intravesical chemotherapy in the last 12 months. Participants with any other cancer diagnosis within the last 5 years (except of skin basaliomas). Acute urinary tract infection Participants with prior radiotherapy or systemic chemotherapy. Participants receiving any other investigational agent or non-marketed product one month prior to Visit 1 and during the trial. Any concurrent illness that may render a participant ineligible or limit compliance with study requirements. Previously enrolled in this trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective is to evaluate the safety and assess the efficacy of intravesical instillation of Alpha1H in subjects with non-muscle invasive bladder cancer ;Secondary Objective: The secondary objective is to further assess the efficacy of Alpha1H in subjects with non-muscle invasive bladder cancer. ;Primary end point(s): Adverse events (AEs); local and systemic Occurrence, intensity and relationship to the active treatment of AEs will be collected during the trial and 30 days after the last active treatment/placebo administration. Safety will also be evaluated by assessment of Vital Signs, ECG and Laboratory parameters. Quantification of cell shedding in urine - Cell shedding into the urine will be used as a biomarker of the tumor response to the Alpha1H peptide-oleate complex. Alpha1H is expected to trigger tumor cell shedding into the urine, based on studies of HAMLET treatment, where intravesical instillations triggered tumor cell shedding in subjects with bladder cancer. - The response of the papillary tumors to Alpha1H will be characterized by in vivo imaging during examination by cystoscopy. The resected tumor will be characterized by histopathology. The Alpha1H peptide-oleate complex is expected to trigger a reduction in tumor size and a change in shape, based on studies of HAMLET in patients with bladder cancer and results from the murine bladder cancer model. ;Timepoint(s) of evaluation of this end point: Adverse events will be recorded longitudinally. Study parameters will be evaluated at each visit before and after instillation of active compound or placebo. Tumor characteristics will be determined at surgery and by analysis of tissue samples obtained at surgery. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Histopathology scoring - Tissue changes will be quantified by histopathology, using established parameters for scoring of Grade and Stage/Invasiveness. Biopsies will be analysed by a designated study pathologist. - Changes in tumor tissue will be characterized by immunohistochemistry for tumor markers, cell death, proliferation, and inflammation. Tissue accumulation of Alpha1H, defined by staining with specific antibodies - Uptake of Alpha1H by tumor tissue will be quantified by staining of tissue sections with specific antibodies. Uptake will be compared to healthy tissue in individual hosts. Tumor response to Alpha1H by gene expression analysis - Changes in cancer-associated pathways will be analysed in tumor biopsies by whole genome transcriptional profiling. Changes in cancer-associated signalling pathways will be compared between the treatment and placebo groups. Urine cytology and apoptosis - Cells in urine will be quantified before and after Alpha1H instillation, using standard cytology techniques and parameters defining tumor grade and stage. - Apoptotic changes in the shed cells will be quantified, as well as other markers of cell death. Proteomic analysis of markers in urine - Changes in protein markers will be quantified by comparing samples obtained before and after the instillation of Alpha1H.;Timepoint(s) of evaluation of this end point: Study parameters will be evaluated at each visit before and after instillation of active compound or placebo. Tumor characteristics will be determined at surgery and by analysis of tissue samples obtained at surgery. | — |
Countries
Czech Republic
Contacts
Public ContactMats Parsson, CEO
Hamlet Pharma AB
Outcome results
None listed