Bladder Tumor, Bladder Tumors, Urothelial Carcinoma Bladder, Urothelial Carcinoma (UC)
Conditions
Keywords
calcium electroporation, electroporation, transurethral electroporation, bladder tumors, urothelial tumor
Brief summary
This phase I study evaluates intravesical calcium electroporation (CaEP) with a new transurethral electrode. The study is primarily designed to assess the safety of CaEP and secondarily, to preliminary explore the efficacy in patients with limited alternative therapies. The anticipated benefits and structured safety precautions justify the ethical conduct of the investigation.
Interventions
PROCEDURECalcium electroporation
Calcium electroporation involves injection of calcium gluconate into the urinary bladder tumor followed by short, electric pulses (electroporation) with the transurethral electrode
DRUGIntratumoral calcium injection
Intratumoral injection of calcium gluconate in the urinary bladder
DEVICETransurethral electroporation
After injection of calcium into tumor, electroporation is applied using the transurethral electrode
Sponsors
Juan Luis Vásquez
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
The study is a phase I, exploratory, single-arm safety study with 20 patients
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years and able to understand participant information and give informed consent * Histologically verified urothelial bladder tumor * Unfit for cystectomy and/or radiotherapy * Patients with recurrence after radiotherapy unfit for salvage cystectomy * Disease where other treatments are considered unsuitable or have been declined by the patient * The patient may receive simultaneous systemic treatment * Selected high-burden non-muscle-invasive bladder tumors after MDT assessment * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2 * Life expectancy of ≥ 3 months * Patients must be deemed able to tolerate general anesthesia * Sexually active participants in the reproductive age must use contraception. Accepted contraception includes the use of intrauterine device (IUD), oral contraceptives, male or female condom, vasectomy or female sterilization * Patients must stop treatment with anticoagulants before surgery in accordance with national guidelines * Plasma ionized Ca2+ must be within the normal upper limit. Correction is allowed * Hematology * Thrombocytes ≥ 50 billion/L * International normalized ratio (INR) ≤ 1.5. Correction is allowed
Exclusion criteria
* Pregnancy (confirmed by a blood sample) or lactation * Allergy to calcium gluconate or any of its excipients * Any clinical condition or previous treatment, that in the investigators' opinion made the patient ineligible * Contraindications to treatment with calcium gluconate as described: * Hypersensitivity to calcium gluconate or any of its excipients * Hypercalcemia (e.g. due to hyperparathyroidism, hypervitaminosis D, decalcifying malignancies, renal insufficiency, immobilization osteoporosis, sarcoidosis, milk-alkali syndrome)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety within 3 months post-treatment assessed by adverse and serious adverse events. | From treatment to follow-up after 3 months | Safety within 3 months post-treatment assessed by adverse and serious adverse events (CTCAE ver. 6.0). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety within 12 months post-treatment assessed by adverse and serious adverse events. | From treatment to 12 months follow-up | Safety within 12 months post-treatment assessed by adverse and serious adverse events (CTCAE ver. 6.0). |
| Response rate of tumor | From treatment to 12 months follow-up | Response rate of tumor will be evaluated by visualization of the treated area with cystoscopy and biopsies of tumor or tumor site in case of remission. Using an adaptation of the revised RECIST ver. 1.1 criteria the response to treatment will be evaluated |
| Local control of tumor | From treatment to 12 months follow-up | Local control of tumor will be evaluated by visualization of the treated area with cystoscopy and biopsies of tumor or tumor site in case of remission. Using an adaptation of the revised RECIST ver. 1.1 criteria the response to treatment will be evaluated |
| Tumor response to CaEP | From treatment to 12 months follow-up | A biopsy at every follow-up will be histologically examined for presence of malignancy and immune cell infiltration (hematoxylin and eosin (H\&E) stain) |
| Dissemination of tumor to other sites of the bladder | From treatment to 12 months follow-up | Dissemination of tumor to other sites of the bladder will be evaluated by visualization by cystoscopy and biopsy |
| Metastasis of tumor to other sites in the body will be evaluated by CT scan | From treatment to 12 months follow-up | — |
| Time to progression evaluated by the revised RECIST criteria on CT scan | From treatment to 12 months follow-up | — |
| Progression-free survival rate evaluated by cystoscopy, biopsy and CT scan | From treatment to 12 months follow-up | — |
| Evaluation of quality of life using EORTC-QLQ-C30 before treatment and at follow-up | From treatment to 12 months follow-up | Quality of life assessed by the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC-QLQ-C30). The questionnaire consists of three scales, and each scale is scored from 0 to 100. Higher scores indicate higher level of function on the the functional scale and higher quality of life on the global health scale, but higher level of symptomatology on the symptom scale. |
| Evaluation of urinary symptoms registered in the ICIQ-FLUTS/ICIQ-MLUTS | From treatment to 12 months follow-up | Urinary symptoms registered using the International Consultation on Incontinence Questionnaire Female/Male Lower Urinary Tract Symptoms Modules (ICIQ-FLUTS (0-48 points)/ICIQ-MLUTS (0-44 points). Higher level of points indicate higher level of symptoms. |
| Evaluation of sexual matters registered in the ICIQ-FLUTSsex/ICIQ-MLUTSsex | From treatment to 12 months follow-up | Evaluation of sexual matters using the International Consultation on Incontinence Questionnaire Female/Male Sexual Matters Associated with Lower Urinary Tract Symptoms Module (ICIQ-FLUTSsex (0-14 points)/ICIQ-MLUTSsex (0-12 points)). Greater values indicating increasing problems with sexual matters. |
| All-cause mortality and cancer related mortality within 12 months | From treatment to 12 months follow-up | — |
| Experiences and opinions of up to ten of the patients that participate in the qualitative interviews | From treatment to 3 months follow-up | A subset of up to 10 patients will participate in the qualitative interviews at 3 months. |
| Concentration of calcium in a blood sample before injection of calcium gluconate 30 minutes and 2 hours after injection | Before treatment (Baseline), 30 minutes after injection of calcium gluconate, and 2 hours after injection of calcium gluconate | — |
Contacts
CONTACTJuan Luis Vásquez
Outcome results
None listed