Clinical trial NCT01829971: A Multicenter Phase I Study of MRX34, MicroRNA miR-RX34 Liposomal Injection
Official title: A Multicenter Phase I Study of MRX34, MicroRNA miR-RX34 Liposomal Injection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Primary Liver Cancer
SCLC
Lymphoma
Melanoma
Multiple Myeloma
Renal Cell Carcinoma
NSCLC
Keywords: microRNA
Advanced cancer
Lead sponsor: Mirna Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Cancer Prevention Research Institute of Texas
First posted: 2013-04-11
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Aged ≥ 18 years
2. Patients with histologically confirmed viral related hepatocellular, SCLC, non-cutaneous/ non-uveal melanoma, ovarian, TNBC, Sarcoma, Bladder and RCC.
3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
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. 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, heart 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 coumadin-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.

Primary outcomes:
measure: The maximum tolerated dose (MTD) for MRX34 and the recommended phase 2 dose (RPh2D)
timeFrame: 18 months
Secondary outcomes:
measure: Peak blood concentration and Area Under the Curve (AUC) of MRX34 after IV dosing
timeFrame: 18 months
measure: Number of patients with evidence of clinical activity of MRX34
timeFrame: 18 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Virginia G. Piper Cancer Center
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Dallas
country: United States
facility: Texas Oncology Dallas
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Uthscsa/Ctrc
state: Texas
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsie University Health System
state: Seodaemun-Gu
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: Mirna Therapeutics
name: O'Neill VIncent, MD
role: STUDY_DIRECTOR
References:
citation: Lucibello G, Mograbi B, Milano G, Hofman P, Brest P. PD-L1 regulation revisited: impact on immunotherapeutic strategies. Trends Mol Med. 2021 Sep;27(9):868-881. doi: 10.1016/j.molmed.2021.06.005. Epub 2021 Jun 26.
citation: Hong DS, Kang YK, Borad M, Sachdev J, Ejadi S, Lim HY, Brenner AJ, Park K, Lee JL, Kim TY, Shin S, Becerra CR, Falchook G, Stoudemire J, Martin D, Kelnar K, Peltier H, Bonato V, Bader AG, Smith S, Kim S, O'Neill V, Beg MS. Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours. Br J Cancer. 2020 May;122(11):1630-1637. doi: 10.1038/s41416-020-0802-1. Epub 2020 Apr 2.