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

Primary Purpose

Primary Liver Cancer, SCLC, Lymphoma

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
MRX34
Sponsored by
Mirna Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Liver Cancer focused on measuring microRNA, Advanced cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Virginia G. Piper Cancer Center
  • Mayo Clinic Arizona
  • Texas Oncology Dallas
  • UT Southwestern Medical Center
  • MD Anderson Cancer Center
  • Uthscsa/Ctrc
  • Severance Hospital, Yonsie University Health System
  • Seoul National University Hospital
  • Samsung Medical Center
  • Asan Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

MRX34

Arm Description

Single agent MRX34

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Peak blood concentration and Area Under the Curve (AUC) of MRX34 after IV dosing
Number of patients with evidence of clinical activity of MRX34

Full Information

First Posted
April 8, 2013
Last Updated
September 26, 2016
Sponsor
Mirna Therapeutics, Inc.
Collaborators
Cancer Prevention Research Institute of Texas
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1. Study Identification

Unique Protocol Identification Number
NCT01829971
Brief Title
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

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Terminated
Why Stopped
Five immune related serious adverse events
Study Start Date
April 2013 (undefined)
Primary Completion Date
March 2017 (Anticipated)
Study Completion Date
May 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mirna Therapeutics, Inc.
Collaborators
Cancer Prevention Research Institute of Texas

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Liver Cancer, SCLC, Lymphoma, Melanoma, Multiple Myeloma, Renal Cell Carcinoma, NSCLC
Keywords
microRNA, Advanced cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
155 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MRX34
Arm Type
Experimental
Arm Description
Single agent MRX34
Intervention Type
Drug
Intervention Name(s)
MRX34
Intervention Description
micro RNA therapy
Primary Outcome Measure Information:
Title
The maximum tolerated dose (MTD) for MRX34 and the recommended phase 2 dose (RPh2D)
Description
Dose-limiting toxicity (DLT) in 3-6 patients at the end of one treatment cycle
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Peak blood concentration and Area Under the Curve (AUC) of MRX34 after IV dosing
Time Frame
18 months
Title
Number of patients with evidence of clinical activity of MRX34
Time Frame
18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
O'Neill VIncent, MD
Organizational Affiliation
Mirna Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Virginia G. Piper Cancer Center
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
Mayo Clinic Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Texas Oncology Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Uthscsa/Ctrc
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Severance Hospital, Yonsie University Health System
City
Seoul
State/Province
Seodaemun-Gu
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34187739
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.
Results Reference
derived
PubMed Identifier
32238921
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.
Results Reference
derived

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

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