Close
Close

MesomiR 1: A Phase I Study of TargomiRs as 2nd or 3rd Line Treatment for Patients With Recurrent MPM and NSCLC

Access Programs

Disease Information

Descriptive Information
Brief Title † MesomiR 1: A Phase I Study of TargomiRs as 2nd or 3rd Line Treatment for Patients With Recurrent MPM and NSCLC
Official Title † MesomiR 1: A Phase I Study of Intravenously Administered Epidermal Growth Factor Receptor -Targeted, EnGeneIC Delivery Vehicle (EDV)-Packaged, miR-16 Mimic (TargomiRs) for Patients With Malignant Pleural Mesothelioma (MPM) and Advanced Non-Small Cell Lung Cancer (NSCLC) Failing on Std Therapy
Brief Summary The first testing of TargomiRs in the human setting: dose-finding studies in patients with recurrent malignant pleural mesothelioma and non-small cell lung cancer
Detailed Description TargomiRs are targeted minicells containing a microRNA mimic. They consist of three components: 1. A miR-16-based microRNA mimic. The miR-16 family has been implicated as a tumour suppressor in a range of cancer types. The mimic is a double-stranded, 23 base pair, synthetic RNA molecule. 2. Drug delivery vehicle - EDVs. EDVs are nonliving bacterial minicells (nanoparticles). They function as leak resistant micro-reservoir carriers that allow efficient packaging of a range of different drugs, proteins or nucleic acids. 3. Targeting moiety. The EDVs are targeted to EGFR-expressing cancer cells with an anti-EGFR bispecific antibody. TargomiRs are IV injected. Phase 1 Planned dose levels Dose level 1: 5 billion once a week Dose level 2: 5 billion twice a week Dose level 3: 5 billion once a week with cardiac monitoring Dose level 4: 2.5 billion twice and week with cardiac monitoring Dose level 5: as above with an additional dexamethasone challenge All patients begin on a micro dose of 1 billion once a week and escalate to the full phase 1 dose for their dose level on week 3. Duration of treatment for each dose level is on a patient by patient basis. Officially the cycle is 8 weeks long however a patient can continue on treatment if they are deriving clinical benefit from the treatment. If at any time point before or after the 8 week mark, a patient progresses, experiences ongoing or unreasonable toxicities or withdraws from the study, they will cease treatment. Escalation of dose in cohorts of 3-6 patients per dose level. If at least 2 patients are observed to experience Dose Limiting Toxicity (DLT), the prior dose level is defined as the MTD. Adherence to the protocol tends not to be problematic in patient groups where the trial treatment is their only treatment option. They are often very keen to participate and motivated to be part of the research.
Study Phase Phase 1
Study Type † Interventional
Study Design †
Primary Outcome Measure † There is a composite primary outcome to establish maximum tolerated dose and dose limiting toxicities The MTD will be determined by the assessment of dose limiting toxicities.
Secondary Outcome Measure † QOL assessment
Condition † Malignant Pleural Mesothelioma Non-Small Cell Lung Cancer
Intervention † DrugTargomiRs
Study Arms / Comparison Groups Single arm, open label TargomiRs TargomiRs are IV injected. Phase 1 Planned dose levels Dose level 1: 5 billion once a week Dose level 2: 5 billion twice a week Dose level 3: 5 billion once a week with cardiac monitoring Dose level 4: 2.5 billion twice a week with cardiac monitoring Dose level 5: as for dose level #3 with a dexamethasone challenge All patients begin on a micro dose of one billion and increase their dose over 2 weeks and reach their phase 1 dose level on week 3. Schedule of assessments includes laboratory and physical assessments in the 24 hours after each treatment as well as periodic assessments such as PET and CT scans for tumour assessment. 100% of the data will be source data verified. Analysis will be simple phase 1 analysis based on a 3+3 model.
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Drug
Estimated Enrollment † 27
Start Date † September 2014
Completion Date January 4, 2017
Primary Completion Date January 4, 2017
Eligibility Criteria † Inclusion Criteria: Histological or cytological documentation of MPM or NSCLC and evidence of EGFR expression in tumour tissue. Progression during or following the administration of standard 1st, 2nd or 3rd line therapy regimens. Patient must have at least one measurable lesion according to the RECIST criteria version 1.1 for NSCLC and modified RECIST criteria for MPM Male or female patients at least 18 years of age. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Life expectancy of at least 3 months. Women of childbearing potential and men must agree to use adequate contraception from the time of signing of the informed consent form until at least 3 months after the last study drug administration. Total bilirubin 60 ml/min/m2 INR/PTT 100.000 and 9 g/dl, Absolute Neutrophil count (ANC) > 1500/mm3. Alkaline phosphatase limit New York Heart Association (NYHA) class 2. Unstable angina (angina at rest) or new-onset angina ( 150 mmHg or diastolic pressure > 90 mm Hg despite optimal medical management). Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including Transient Ischemic Attacks), deep vein thrombosis or pulmonary embolism within 6 months before the screening radiographic studies. Ongoing infection > grade 2 NCI-CTCAE version 4.0 HIV infection. Chronic hepatitis B or C. Patients with a seizure disorder requiring medication. Symptomatic brain metastasis(es). The patient must not be undergoing acute steroid therapy or steroid tapering (Chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies). Patients with a history of bleeding diathesis: Any hemorrhage or bleeding event of CTCAE Grade 3 within 4 weeks of the proposed start of study medication. Renal failure requiring hemo-or peritoneal dialysis. Substance abuse, medical, psychological or social conditions that in the opinion of the investigator may interfere with the patient's participation in the study or evaluation of the study results. Known hypersensitivity to bacterial proteins. Any medical condition that is unstable or could jeopardize the safety of the patient and his/her compliance in the study. Unresolved toxicity higher than NCI-CTCAE (version 4.0) Grade 2 attributed to any prior therapy/procedure excluding alopecia.
Gender All
Ages 18 Years - N/A
Accepts Healthy Volunteers No
Contacts ††
Location Countries † Australia
Administrative Information
NCT ID † NCT02369198
Organization ID HREC/13/CRGH/199
Secondary IDs ††
Responsible Party Sponsor
Study Sponsor † Asbestos Diseases Research Foundation
Collaborators †† EnGeneIC Limited
Investigators † Principal Investigator: Nico vanZandwijk, PhD, University of Sydney
Information Provided By
Verification Date April 2017
First Received Date † January 5, 2015
Last Updated Date April 5, 2017
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
Find a Clinical Trial
Related Videos
by Abidemi Uruejoma
563 views
by Abidemi Uruejoma
4,168 views
by Abidemi Uruejoma
9,926 views
by Dr. Jules Richard Kemadjou
10,127 views
Free Newsletter