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

Study ID
STU 012013-066

Study Sites

  • Clements University Hospital

Contact
Joyce Bolluyt
2146487007
joyce.bolluyt@utsouthwestern.edu

Principal Investigator
Muhammad Beg

Official Title

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

Brief Overview

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.

Description

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).

Eligibility

Inclusion Criteria:
1. Aged ≥ 18 years
2. Patients with histologically confirmed unresectable primary liver cancer or advanced metastatic cancer with or without liver metastasis (melanoma, SCLC, NSCLC). For the hematologic malignancy cohorts, patients with ALL, CLL, CML in accelerated or blast phase, lymphoma, MM or MDS may be enrolled
3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
4. 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.
5. 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
6. 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.
7. 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
8. 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:
1. New York Heart Association (NYHA) Class III or IV cardiac disease, myocardial infarction within the past 6 months, unstable and/or symptomatic arrhythmia, or evidence of ischemia on ECG.
2. Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy.
3. Pregnant or nursing women.
4. Known infection with human immunodeficiency virus (HIV).
5. Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor.
6. Patients with recent history of hemorrhage and patients predisposed to hemorrhage due to coagulopathies or structural anomalies.
7. Patients who require treatment with therapeutic doses of coumarin-type anticoagulants (maximum daily dose of 1mg allowed for port line patency permitted).
8. Patients with cirrhosis classed as Child-Pugh B or C.
9. Patients with central nervous system (CNS) metastasis. Intrathecal chemotherapy is allowed for patients who require CNS prophylaxis or therapy.
10. Patients for whom dexamethasone is contraindicated.