Metastatic urothelial cancer MedDRA version: 20.0 Level: LLT Classification code 10064467 Term: Urothelial carcinoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Stromectol
Pharmaceutical Form: Tablet
INN or Proposed INN: IVERMECTIN
CAS Number: 70288-86-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-
Trade
Sponsors
Ectin Research AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed Informed Consent Form before any screening procedures 2. = 18 years of age on the day of giving informed consent 3. Confirmed current metastatic urothelial carcinoma of the bladder, including the urethra and upper urinary tract. The patient needs to have progressive disease and/or symptomatic metastatic disease that is unresponsive to standard therapy. The patient must have received all available approved therapies before being eligible for the study unless contraindications or intolerance exist for one or several of them 4. At least one lesion of measurable disease as defined by RECIST1.1 criteria based on CT or MRI scan made within 2 weeks before ibuprofen-start at Day -7 5. World Health Organization (WHO) performance status 0-2 6. Life expectancy =12 weeks 7. Patients with reproductive potential will need to use accepted and highly effective means of contraception from study entry until at least 6 weeks for females (women of childbearing potential, WOCP) and 3 months for males after study drug discontinuation 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 12 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 38
Exclusion criteria
Exclusion criteria: 1. Known CNS metastatic lesions, or evidence of impaired blood-brain barrier as assessed by the investigator 2. Have signs or symptoms of active COVID-19 infection or a positive COVID-19 PCR test during the screening period 3. Impaired renal function by estimated Glomerular Filtration Rate (eGFR) <30 ml/min as per local assessment 4. Laboratory values (hematology and biochemistry) within specified ranges to show appropriate organ function 5. Clinically significant cardiac disease, 6. Untreated or uncontrolled hypertension 7. An underlying medical condition that precludes the ability to take oral medication daily 8. Concomitant therapy that precludes enrolment: - Concomitant use of other nonsteroidal anti-inflammatory drugs (NSAIDs). Wash out and change of treatment is allowed during the screening period and up to one week before visit 2 - Treatment in a prior investigational study within four weeks before enrolment or within five half-lives of the investigational product, whichever is longer, before starting study drug (visit 2) 9. The patient has had biologic, hormonal, anti-neoplastic chemotherapy within 4 weeks prior to screening except for medications with half-lives <5.5 days, or radiation therapy other than palliative treatment within 2 weeks 10. Hypersensitivity to ibuprofen, ivermectin, avermectin, or any of the excipients listed in section 6.1 in respective SmPC 11. Any bleeding disorder or condition where there is an increased risk of bleeding 12. A history of allergic reactions following intake of acetylsalicylic acid or NSAIDs 13. A history of gastrointestinal bleeding or perforation 14. Active or recurrent gastrointestinal ulcer 15. The known or suspected presence of a tropical parasitic infection, such as strongyloidiasis, onchocerciasis, or any other for which treatment with ivermectin is indicated 16. Major surgery within 14 days before enrolment. (Note: trans-urethral resection of bladder tumor is not considered major surgery) 17. For female patients of childbearing potential – pregnancy, as confirmed by a serum pregnancy test at screening, or breast-feeding 18. Any other severe, acute, or chronic medical condition that would interfere with the conduct of the study or interpretation of the study results as judged by the investigator 19. The patient has already participated in the study or been a screening failure
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part I: To characterise the safety and tolerability of MFA-370 Part II: To assess the anti-tumor activity of MFA-370 ;Secondary Objective: To assess the anti-tumor activity of MFA-370 To characterise the safety and tolerability of MFA-370 To assess survival To characterise the pharmacokinetic properties of MFA-370;Primary end point(s): Part I: - Safety: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) with a causal relationship to MFA-370 - Tolerability: Incidence of dose interruptions, reductions, and treatment terminations due to AEs/SAEs Part II: - Efficacy: Overall Response Rate (ORR) at Week 24, assessed by the investigator based on the assessment of the CT/MR-scans made by the responsible Radiologist at each site (scans assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1) ;Timepoint(s) of evaluation of this end point: - Safety and tolerability: Continuously up to 30 days safety follow up - Overall Response Rate: At 24 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Anti-tumor activity: ORR, Clinical Benefit Rate (CBR), Progression-Free Survival (PFS), Time to Progression (TTP), Best Overall Response (BOR) (based on CT/MR-scans assessed by Radiologist per RECIST 1.1) - Safety: Incidence and severity of AEs and SAEs with a causal relationship to MFA-370 - Tolerability: Incidence of dose interruptions, reductions, and treatment terminations due to AEs - Overall survival (OS) - Pharmacokinetic (PK) parameters for ibuprofen and ivermectin, including but not limited to; time vs plasma concentration profiles, Cmax, tmax, t1/2;Timepoint(s) of evaluation of this end point: - Anti-tumor activity: Every six weeks - Safety and tolerability: Continuously up to 30 days after last dose - Overall survival: from the last dose until the date of death - Pharmacokinetic (PK) parameters: Visit 2, 3, 4, 5, 6, 7, 9, 10, 24 | — |
Countries
Denmark, Germany, Lithuania, Sweden
Contacts
Public ContactAnna Sjöblom-Hallén
Ectin Research AB
Outcome results
None listed