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

Study ID
MRX34-101

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

  • Clements University Hospital
  • UT Southwestern Ambulatory Services
  • Zale Lipshy University Hospital

Contact
Joyce Bolluyt
214/648-7007
joyce.bolluyt@utsouthwestern.edu

Principal Investigator
Muhammad Beg, M.D.

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.

Summary


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).

Participant 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 lymphoma or MM 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.