PMID- 27917453
OWN - NLM
STAT- MEDLINE
DCOM- 20171214
LR  - 20220414
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Print)
IS  - 0167-6997 (Linking)
VI  - 35
IP  - 2
DP  - 2017 Apr
TI  - Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in 
      patients with advanced solid tumors.
PG  - 180-188
LID - 10.1007/s10637-016-0407-y [doi]
AB  - Purpose Naturally occurring tumor suppressor microRNA-34a (miR-34a) downregulates 
      the expression of >30 oncogenes across multiple oncogenic pathways, as well as 
      genes involved in tumor immune evasion, but is lost or under-expressed in many 
      malignancies. This first-in-human, phase I study assessed the maximum tolerated 
      dose (MTD), safety, pharmacokinetics, and clinical activity of MRX34, a liposomal 
      miR-34a mimic, in patients with advanced solid tumors. Patients and Methods Adult 
      patients with solid tumors refractory to standard treatment were enrolled in a 
      standard 3 + 3 dose escalation trial. MRX34 was given intravenously twice weekly 
      (BIW) for three weeks in 4-week cycles. Results Forty-seven patients with various 
      solid tumors, including hepatocellular carcinoma (HCC; n = 14), were enrolled. 
      Median age was 60 years, median prior therapies was 4 (range, 1-12), and most 
      were Caucasian (68%) and male (57%). Most common adverse events (AEs) included 
      fever (all grade %/G3%: 64/2), fatigue (57/13), back pain (57/11), nausea (49/2), 
      diarrhea (40/11), anorexia (36/4), and vomiting (34/4). Laboratory abnormalities 
      included lymphopenia (G3%/G4%: 23/9), neutropenia (13/11), thrombocytopenia 
      (17/0), increased AST (19/4), hyperglycemia (13/2), and hyponatremia (19/2). 
      Dexamethasone premedication was required to manage infusion-related AEs. The MTD 
      for non-HCC patients was 110 mg/m(2), with two patients experiencing 
      dose-limiting toxicities of G3 hypoxia and enteritis at 124 mg/m(2). The 
      half-life was >24 h, and C(max) and AUC increased with increasing dose. One 
      patient with HCC achieved a prolonged confirmed PR lasting 48 weeks, and four 
      patients experienced SD lasting >/=4 cycles. Conclusion MRX34 treatment with 
      dexamethasone premedication was associated with acceptable safety and showed 
      evidence of antitumor activity in a subset of patients with refractory advanced 
      solid tumors. The MTD for the BIW schedule was 110 mg/m(2) for non-HCC and 
      93 mg/m2 for HCC patients. Additional dose schedules of MRX34 have been explored 
      to improve tolerability.
FAU - Beg, Muhammad S
AU  - Beg MS
AD  - Division of Hematology/Oncology, University of Texas (UT) Southwestern Medical 
      Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390-8852, USA. 
      Muhammad.Beg@UTSouthwestern.edu.
FAU - Brenner, Andrew J
AU  - Brenner AJ
AD  - UT Health Science Center, San Antonio, TX, USA.
FAU - Sachdev, Jasgit
AU  - Sachdev J
AD  - Scottsdale Healthcare Research Institute, Scottsdale, AZ, USA.
FAU - Borad, Mitesh
AU  - Borad M
AD  - Mayo Clinic Cancer Center, Scottsdale, AZ, USA.
FAU - Kang, Yoon-Koo
AU  - Kang YK
AD  - Asan Medical Center, Seoul, South Korea.
FAU - Stoudemire, Jay
AU  - Stoudemire J
AD  - Mirna Therapeutics, Inc, Austin, TX, USA.
FAU - Smith, Susan
AU  - Smith S
AD  - Mirna Therapeutics, Inc, Austin, TX, USA.
FAU - Bader, Andreas G
AU  - Bader AG
AD  - Mirna Therapeutics, Inc, Austin, TX, USA.
FAU - Kim, Sinil
AU  - Kim S
AD  - Mirna Therapeutics, Inc, Austin, TX, USA.
FAU - Hong, David S
AU  - Hong DS
AD  - UT MD Anderson Cancer Center, Houston, TX, USA.
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
DEP - 20161205
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Liposomes)
RN  - 0 (MIRN34 microRNA, human)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/*administration & dosage/adverse 
      effects/pharmacokinetics/therapeutic use
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Liposomes
MH  - Male
MH  - Maximum Tolerated Dose
MH  - MicroRNAs/*administration & dosage/adverse effects/pharmacokinetics/therapeutic 
      use
MH  - Middle Aged
MH  - Nanoparticles/administration & dosage/adverse effects
MH  - Neoplasms/*drug therapy/metabolism
MH  - Treatment Outcome
PMC - PMC5893501
MID - NIHMS955503
OTO - NOTNLM
OT  - Advanced solid tumors
OT  - Experimental therapeutics
OT  - Phase I trial
OT  - miR-34a
OT  - microRNA
EDAT- 2016/12/06 06:00
MHDA- 2017/12/15 06:00
PMCR- 2018/04/11
CRDT- 2016/12/06 06:00
PHST- 2016/10/17 00:00 [received]
PHST- 2016/11/09 00:00 [accepted]
PHST- 2016/12/06 06:00 [pubmed]
PHST- 2017/12/15 06:00 [medline]
PHST- 2016/12/06 06:00 [entrez]
PHST- 2018/04/11 00:00 [pmc-release]
AID - 10.1007/s10637-016-0407-y [pii]
AID - 10.1007/s10637-016-0407-y [doi]
PST - ppublish
SO  - Invest New Drugs. 2017 Apr;35(2):180-188. doi: 10.1007/s10637-016-0407-y. Epub 
      2016 Dec 5.