A Multicenter Phase I Study of MRX34, MicroRNA miR-RX34 Liposomal Injection

Study Overview
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Brief Summary
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This is a study to evaluate the safety of MRX34 in patients with primary liver cancer or other selected solid tumors or hematologic malignancies. The drug is given intravenously, for 5 days in a row and then two weeks off.

Detailed Description
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This is a Phase I, open-label, multicenter, dose-escalation study to investigate the safety, Pharmacokinetics and Pharmacodynamics of the micro ribonucleic acid (microRNA) MRX34, in patients with unresectable primary liver cancer or advanced or metastatic cancer with or without liver involvement or hematologic malignancies. MRX34 will be administered daily x 5 with 2 weeks off (total of 21 days) for 3 cycles followed by a no-treatment observation period.

Official Title
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A Multicenter Phase I Study of MRX34, MicroRNA miR-RX34 Liposomal Injection

Conditions
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Primary Liver Cancer, SCLC, Lymphoma, Melanoma, Multiple Myeloma, Renal Cell Carcinoma, NSCLC

Intervention / Treatment
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* Drug: MRX34


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 18 years Patients with histologically confirmed viral related hepatocellular, SCLC, non-cutaneous/ non-uveal melanoma, ovarian, TNBC, Sarcoma, Bladder and RCC. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 Acceptable liver function: Total bilirubin ≤ 1.5 times the upper limit of normal (ULN); for patients with hepatocellular carcinoma only, total bilirubin ≤ 3 mg/dL (i.e. Child-Pugh Score for bilirubin is no greater than 2). Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) ≤ 5 x ULN. Acceptable renal function: • Serum creatinine ≤ 1.5 times the ULN, or calculated creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above 1.5 times the institutional normal Acceptable hematological status: Absolute Neutrophil Count (ANC) ≥ 1500 cells/mm3 Platelet count ≥ 100,000 plts/mm3 (without transfusion); ≥ 75,000 plts/mm3 for patients with hepatocellular carcinoma only. For hematologic malignancy patients blood counts cited above do not apply Hemoglobin ≥ 9 g/dL For the hematologic malignancy patients, blood count values cited above do not apply. Prothrombin time (PT) or International Normalized Ratio (INR) ≤ 1.25 x ULN; for patients with hepatocellular carcinoma only, INR <1.7 or prothrombin time (PT) or < 4 seconds above ULN (i.e. Child-Pugh Score is no greater than 1 for the coagulation parameter); for patients with hepatocellular carcinoma only, serum albumin > 2.8 g/dL (i.e. Child-Pugh Score for albumin is no greater than 2). For the hematologic malignancy patients, the coagulation and albumin status cited above do not apply For patients with hepatocellular carcinoma only, Child-Pugh Class A (score 5-6) disease. Score for hepatic encephalopathy must be 1; the score for ascites must be no greater than 2 and clinically irrelevant; for the determination of the Child-Pugh Class. Exclusion Criteria: Myocardial infarction within the past 6 months, unstable and/or symptomatic arrhythmia, or evidence of ischemia on ECG. Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy. Pregnant or nursing women. Known infection with human immunodeficiency virus (HIV). Serious nonmalignant disease (e.g., hydronephrosis, liver failure, heart failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor. Patients with recent history of hemorrhage and patients predisposed to hemorrhage due to coagulopathies or structural anomalies. Patients who require treatment with therapeutic doses of coumadin-type anticoagulants (maximum daily dose of 1mg allowed for port line patency permitted). Patients with cirrhosis classed as Child-Pugh B or C. Patients with central nervous system (CNS) metastasis. Intrathecal chemotherapy is allowed for patients who require CNS prophylaxis or therapy. Patients for whom dexamethasone is contraindicated.

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MRX34<br>Single agent MRX34 | Drug: MRX34<br>* micro RNA therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The maximum tolerated dose (MTD) for MRX34 and the recommended phase 2 dose (RPh2D) | Dose-limiting toxicity (DLT) in 3-6 patients at the end of one treatment cycle | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak blood concentration and Area Under the Curve (AUC) of MRX34 after IV dosing |  | 18 months | 
| Number of patients with evidence of clinical activity of MRX34 |  | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microRNA, Advanced cancer