A Study of MFA-370 in Patients With Metastatic Urothelial Cancer

Study Overview
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Brief Summary
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This is a multi-center study of MFA-370 in patients with metastatic urothelial cancer. The objective of the study is to assess the safety and efficacy of MFA-370, i.e.a combination of two approved pharmaceuticals today used within other indications. The combination was developed after the finding that a multidiseased man with e.g. muscle-invasive bladder cancer also was treated for his recent parasitic infection resulted in that the parasitic infection together with the cancer got a complete remission. After extensive experimental complementing studies a combination treatment called MFA-370 was developed supporting the rationale for this treatment. This is the first clinical trial where the combination product MFA-370 is evaluated as anti-cancer treatment. Up to 50 patients will participate. MFA-370 is taken orally once daily for up to 24 weeks. If the treatment is of clinical benefit for the patient, as assessed by the investigator, the treatment period can be prolonged to up to 2 years. The patients will be monitored for safety, tolerability, pharmacokinetics, tumor response by RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 and survival.

Official Title
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An Open-label, Multi-center, Phase I/II Study of MFA-370 in Patients With Metastatic Urothelial Cancer

Conditions
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Metastatic Urothelial Cancer

Intervention / Treatment
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* Drug: MFA-370


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent Form before any screening procedures ≥ 18 years of age on the day of giving informed consent 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 At least one lesion of measurable disease as defined by RECIST1.1 criteria based on CT or MRI scan within 2 weeks before start at Day -7 World Health Organization (WHO) performance status 0-2 Life expectancy ≥12 weeks 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) and 3 months for males after study drug discontinuation Main Exclusion Criteria: Known CNS metastatic lesions, or evidence of impaired blood-brain barrier as assessed by the investigator Have signs or symptoms of active COVID-19 infection or a positive COVID-19 Polymerase Chain Reaction (PCR) test during the screening period Impaired renal function by estimated Glomerular Filtration Rate (eGFR) <30 ml/min as per local assessment Laboratory values (hematology and biochemistry) within specified ranges to show appropriate organ function Clinically significant cardiac disease, Untreated or uncontrolled hypertension An underlying medical condition that precludes the ability to take oral medication daily Prohibited concomitant therapy The patient has had biologic, hormonal, anti-neoplastic chemotherapy, or radiation therapy other than palliative treatment within 4 weeks prior to screening except for medications with half-lives <5.5 days Hypersensitivity to the active ingredients or to any of the excipients listed in section 6.1 in respective Summary of Product Characteristics (SmPC) Any bleeding disorder or condition where there is an increased risk of bleeding A history of allergic reactions following intake of acetylsalicylic acid or NSAIDs A history of gastrointestinal bleeding or perforation Active or recurrent gastrointestinal ulcer Major surgery within 14 days before enrolment. (Note: trans-urethral resection of bladder tumor is not considered major surgery) For female patients of childbearing potential - pregnancy, as confirmed by a serum pregnancy test at screening, or breast-feeding 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 The patient has already participated in the study or been a screening failure

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MFA-370<br>MFA-370 once daily for up to 8 x 21 days. | Drug: MFA-370<br>* MFA-370 is a treatment with a combination of two approved pharmaceuticals<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) | Safety of MFA-370 measured by incidence and severity of AEs and serious SAEs with a causal relationship to MFA-370 | Up to 30 days safety follow up | 
| Incidence of dose interruptions, reductions, and treatment terminations due to AEs/SAEs | Tolerability of MFA-370 measured by incidence of dose interruptions, reductions, and treatment terminations due to AEs/SAEs | Up to 30 days safety follow up | 
| Overall Response Rate (ORR) | Anti-tumor activity of MFA-370 measured by Overall Response Rate (ORR), assessed by the investigator based on the assessment of the Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scans made by the responsible Radiologist at each site (scans assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1) | At 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR), Clinical Benefit Rate (CBR), Progression-Free Survival (PFS), Time to Progression (TTP), Best Overall Response (BOR) | Anti-tumor activity of MFA-370 measured by ORR, CBR, PFS, TTP, BOR based on CT/MRI-scans assessed by Radiologist per RECIST 1.1 | Every six weeks up to 24 weeks | 
| Incidence and severity of AEs and SAEs | Safety of MFA-370 measured by incidence and severity of AEs and SAEs with a causal relationship to MFA-370 | Up to 30 days after last dose | 
| Incidence of dose interruptions, reductions, and treatment terminations due to AEs/SAEs | Tolerability of MFA-370 measured by incidence of dose interruptions, reductions, and treatment terminations due to AEs | Up to 30 days after last dose | 
| Overall Survival | Effect of MFA-370 on Overall Survival | From the last dose until the date of death or up to 6 months after the last patient's end of treatment, whichever came first. | 
| Plasma concentration profiles | To characterize the pharmacokinetic properties of MFA-370 with respect to time vs plasma concentration profiles | From start of treatment until 29th day of treatment | 
| Peak Plasma Concentration (Cmax) | To characterize the pharmacokinetic properties of MFA-370 with respect to Cmax in plasma | From start of treatment until 29th day of treatment | 
| Time to reach peak plasma concentration (tmax) of MFA-370 in plasma | To characterize the pharmacokinetic properties of MFA-370 with respect to tmax | From start of treatment until 29th day of treatment | 
| Elimination half-life (t1/2) of MFA-370 in plasma | To characterize the pharmacokinetic properties of MFA-370 with respect to t1/2 | From start of treatment until 29th day of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic Urothelial Cancer