A Phase I/II Randomized Study Evaluating if the study drug Alpha1H is effective and safe in comparison to placebo in adult patients with bladder cancer before planned surgery to remove tumour
- Conditions
- Non-muscle invasive bladder cancer awaiting transurethral surgery
- Registration Number
- 2024-514628-17-00
- Lead Sponsor
- Hamlet BioPharma AB
- Brief Summary
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ended
- Sex
- Not specified
- Target Recruitment
- 76
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
Patient with a previous history of muscle invasive bladder cancer
Previously enrolled in this trial
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 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 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 peptideoleate 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 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 peptideoleate 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
- Secondary Outcome Measures
Name Time Method 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 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 - 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 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 cancerassociated signalling pathways will be compared between the treatment and placebo groups 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 cancerassociated 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 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 Proteomic analysis of markers in urine - Changes in protein markers will be quantified by comparing samples obtained before and after the instillation of Alpha1H
Trial Locations
- Locations (1)
Fakultni Nemocnice V Motole
🇨🇿Prague, Czechia
Fakultni Nemocnice V Motole🇨🇿Prague, CzechiaMarek BajbukSite contact+420224434801marek.babjuk@lf.cuni.fnmotol.cz