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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02369198




Registration number
NCT02369198
Ethics application status
Date submitted
5/01/2015
Date registered
23/02/2015
Date last updated
7/04/2017

Titles & IDs
Public title
MesomiR 1: A Phase I Study of TargomiRs as 2nd or 3rd Line Treatment for Patients With Recurrent MPM and NSCLC
Scientific 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
Secondary ID [1] 0 0
HREC/13/CRGH/199
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Pleural Mesothelioma 0 0
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TargomiRs

Experimental: 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.


Treatment: Drugs: TargomiRs
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
DLTs assessed from treatment 1 for 2 weeks. MTD is measured from first treatment to toxicity (up to 18 months).
Primary outcome [2] 0 0
to evaluate the effect of multiple dosing of TargomiRs
Timepoint [2] 0 0
the lab and physical assessments are conducted from first treatment, multiple times in a 24 hour period after treatment for up to 18 months
Primary outcome [3] 0 0
to detect early signs of efficacy
Timepoint [3] 0 0
8 weeks, when formal assessment with RECIST is applied and QoL questionnaires assessed.
Secondary outcome [1] 0 0
QOL assessment
Timepoint [1] 0 0
Baseline & weekly or twice weekly (depending on patient's cohort) up to 8 weeks
Secondary outcome [2] 0 0
ECOG PS change
Timepoint [2] 0 0
ECOG PS will be assessed from baseline til 8 weeks
Secondary outcome [3] 0 0
Pulmonary function change
Timepoint [3] 0 0
Pulmonary function is measured in screening and at 8 weeks

Eligibility
Key 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 < 1.5 x the upper limit of normal (ULN) ALT and AST < 2.5 x ULN Amylase < 1.5 x ULN Serum creatinine < 1.5 x ULN GFR > 60 ml/min/m2 INR/PTT < 1.5 x ULN (patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. Close monitoring with at least weekly evaluations will be performed until INR/APTT is stable (prior to administering the first dose)).

Platelet count > 100.000 and < 800.000, Hemoglobin (Hb) > 9 g/dl, Absolute Neutrophil count (ANC) > 1500/mm3. Alkaline phosphatase limit < 2.5 x ULN.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previous phase I drug treatment for the current diagnosis. Previous or concurrent cancer that is distinct in primary site or histology from MPM or NSCLC within 10 years from the date of screening EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumours (Ta, Tis and T1).

Presence of Salmonella antibodies. Herbal supplements (such as St John's Wort), nutritional supplements and also (multi)-vitamins taken within the last 30 days prior to dosing on Day 1 (and continued use, if appropriate), must be reviewed and approved by the local investigator.

Major surgical procedures in the last four weeks. Pregnancy or breast-feeding. Congestive heart failure > New York Heart Association (NYHA) class 2. Unstable angina (angina at rest) or new-onset angina (< 3 months). Myocardial infarction less than 6 months before eligibility screening.

Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted).

Uncontrolled hypertension (Systolic blood pressure > 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/01/2017
Sample size
Target
Accrual to date
Final
27
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Sydney
Recruitment hospital [2] 0 0
Chris O'Brien Lifehouse - Sydney
Recruitment hospital [3] 0 0
Northern Cancer Institute - Sydney
Recruitment postcode(s) [1] 0 0
2039 - Sydney
Recruitment postcode(s) [2] 0 0
2050 - Sydney
Recruitment postcode(s) [3] 0 0
2065 - Sydney

Funding & Sponsors
Primary sponsor type
Other
Name
Asbestos Diseases Research Foundation
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
EnGeneIC Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/study/NCT02369198
Trial related presentations / publications
Reid G, Pel ME, Kirschner MB, Cheng YY, Mugridge N, Weiss J, Williams M, Wright C, Edelman JJ, Vallely MP, McCaughan BC, Klebe S, Brahmbhatt H, MacDiarmid JA, van Zandwijk N. Restoring expression of miR-16: a novel approach to therapy for malignant pleural mesothelioma. Ann Oncol. 2013 Dec;24(12):3128-35. doi: 10.1093/annonc/mdt412. Epub 2013 Oct 22.
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.
van Zandwijk N, Pavlakis N, Kao SC, Linton A, Boyer MJ, Clarke S, Huynh Y, Chrzanowska A, Fulham MJ, Bailey DL, Cooper WA, Kritharides L, Ridley L, Pattison ST, MacDiarmid J, Brahmbhatt H, Reid G. Safety and activity of microRNA-loaded minicells in patients with recurrent malignant pleural mesothelioma: a first-in-man, phase 1, open-label, dose-escalation study. Lancet Oncol. 2017 Oct;18(10):1386-1396. doi: 10.1016/S1470-2045(17)30621-6. Epub 2017 Sep 1.
Public notes

Contacts
Principal investigator
Name 0 0
Nico vanZandwijk, PhD
Address 0 0
University of Sydney
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02369198